orphaID	label	genes	n_genes	description	roots
Orphanet:166024	Multiple epiphyseal dysplasia, Al-Gazali type	KIF7	1	Multiple epiphyseal dysplasia, Al-Gazali type is a skeletal dysplasia characterized by multiple epiphyseal dysplasia (see this term), macrocephaly and facial dysmorphism.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:166035	Brachydactyly-short stature-retinitis pigmentosa syndrome	CWC27	1	Brachydactyly-short stature-retinitis pigmentosa syndrome is a rare, genetic, congenital limb malformation syndrome characterized by mild to severe short stature, brachydactyly, and retinal degeneration (usually retinitis pigmentosa), associated with variable intellectual disability, develomental delays, and craniofacial anomalies.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic bone disease
Orphanet:93	Aspartylglucosaminuria	AGA	1	An autosomal recessive lysosomal storage disease belonging to the oligosaccharidosis group (also called glycoproteinosis).	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:585	Multiple sulfatase deficiency	SUMF1	1	Multiple sulfatase deficiency (MSD) is a very rare and fatal lysosomal storage disease characterized by a clinical phenotype that combines the features of different sulfatase deficiencies (whether lysosomal or not) that can have neonatal (most severe), infantile (most common) and juvenile (rare) presentations with manifestations including hypotonia, coarse facial features, mild deafness, skeletal anomalies, ichthyosis, hepatomegaly, developmental delay, progressive neurologic deterioration and hydrocephalus.	Rare genetic bone disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare inborn errors of metabolism;Rare genetic skin disease
Orphanet:118	Beta-mannosidosis	MANBA	1	Beta-mannosidosis is a very rare lysosomal storage disease characterized by developmental delay of varying severity and hearing loss, but that can manifest a wide phenotypic heterogeneity.	Rare genetic neurological disorder;Rare genetic bone disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic cardiac disease
Orphanet:166068	Pontocerebellar hypoplasia type 5	TSEN54	1	Pontocerebellar hypoplasia type 5 (PCH5) is a very rare severe form of PCH (see this terme) with prenatal onset and characterized by fetal onset of clonus or seizures-like activity persisting in infancy and microencephaly leading to early postnatal death. There is significant overlap both in phenotype and in genotype between pontocerebellar hypoplasia types 4 and 5.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:166063	Pontocerebellar hypoplasia type 4	TSEN54	1	Pontocerebellar hypoplasia type 4 (PCH4) is a very rare form of PCH (see this term), characterized by prenatal onset of polyhydramnios and contractures followed by hypertonia, severe clonus, primary hypoventilation leading to an early postnatal death.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:166078	Von Willebrand disease type 1	VWF	1	Type 1 von Willebrand disease (type 1 VWD) is a form of VWD (see this term) characterized by a bleeding disorder associated with a partial quantitative plasmatic deficiency of an otherwise structurally and functionally normal Willebrand factor (von Willebrand factor; VWF).	Rare genetic hematologic disease
Orphanet:166073	Pontocerebellar hypoplasia type 6	RARS2	1	Pontocerebellar hypoplasia type 6 (PCH6) is a rare form of pontocerebellar hypoplasia (see this term) characterized clinically at birth by hypotonia, clonus, epilepsy impaired swallowing and from infancy by progressive microencephaly, spasticity and lactic acidosis.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:333	Farber disease	ASAH1	1	A subcutaneous tissue disease characterized by a spectrum of clinical signs ranging from the classical triad of painful and progressively deformed joints, subcutaneous nodules, and progressive hoarseness (due to laryngeal involvement) that presents in infancy, to varying phenotypes with respiratory and neurologic involvement.	Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic skin disease;Rare inborn errors of metabolism
Orphanet:166084	Von Willebrand disease type 2A	VWF	1	Type 2A von Willebrand disease (type 2A VWD) is a subtype of type 2 VWD (see this term) characterized by a bleeding disorder associated with a decrease in the affinity of the Willebrand factor (von Willebrand factor; VWF) for platelets and the subendothelium caused by a deficiency of high molecular weight VWF multimers.	NA
Orphanet:349	Fucosidosis	FUCA1	1	Fucosidosis is an extremely rare lysosomal storage disorder characterized by a highly variable phenotype with common manifestations including neurologic deterioration, coarse facial features, growth retardation, and recurrent sinopulmonary infections, as well as seizures, visceromegaly, angiokeratoma and dysostosis.	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic cardiac disease
Orphanet:166090	Von Willebrand disease type 2M	VWF	1	Type 2M von Willebrand disease (type 2M VWD) is a subtype of type 2 VWD (see this term) characterized by a bleeding disorder associated with a decrease in the affinity of the Willebrand factor (von Willebrand factor; VWF) for platelets and the subendothelium in the absence of any deficiency of high molecular weight VWF multimers.	NA
Orphanet:366	Glycogen storage disease due to glycogen debranching enzyme deficiency	AGL	1	Glycogen debranching enzyme (GDE) deficiency, or glycogen storage disease type 3 (GSD 3), is a form of glycogen storage disease characterized by severe muscle weakness and hepatopathy.	Rare genetic hepatic disease;Rare inborn errors of metabolism;Rare genetic neurological disorder;Rare genetic cardiac disease
Orphanet:166087	Von Willebrand disease type 2B	VWF	1	Type 2B von Willebrand disease (type 2B VWD) is a subtype of type 2 VWD (see this term) characterized by a bleeding disorder associated with an increase in the affinity of the Willebrand factor (von Willebrand factor; VWF) for platelets. This anomaly results in spontaneous binding of high molecular weight VWF multimers to platelets leading to rapid clearance of both the platelets (increasing the risk of thrombocytopenia) and the high molecular weight VWF multimers from the plasma.	NA
Orphanet:368	Glycogen storage disease due to muscle glycogen phosphorylase deficiency	PYGM	1	Myophosphorylase deficiency (McArdle's disease), or glycogen storage disease type 5 (GSD5) , is a severe form of glycogen storage disease characterized by exercise intolerance.	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:166093	Von Willebrand disease type 2N	VWF	1	Type 2N von Willebrand disease (type 2N VWD) is a subtype of type 2 VWD (see this term) characterized by a bleeding disorder associated with a marked decrease in the affinity of the Willebrand factor (von Willebrand factor; VWF) for factor VIII (FVIII).	NA
Orphanet:166096	Von Willebrand disease type 3	VWF	1	Type 3 von Willebrand disease (type 3 VWD) is the most severe form of VWD (see this term) characterized by a bleeding disorder associated with a total or near-total absence of Willebrand factor (von Willebrand factor; VWF) in the plasma and cellular compartments, also leading to a profound deficiency of plasmatic factor VIII (FVIII).	Rare genetic hematologic disease
Orphanet:371	Glycogen storage disease due to muscle phosphofructokinase deficiency	PFKM	1	Muscle phosphofructokinase (PFK) deficiency (Tarui's disease), or glycogen storage disease type 7 (GSD7), is a rare form of glycogen storage disease characterized by exertional fatigue and muscular exercise intolerance. It occurs in childhood.	Rare inborn errors of metabolism;Rare genetic neurological disorder;Rare genetic hematologic disease
Orphanet:166100	Stickler syndrome type 3	COL11A2	1	Stickler syndrome type 3 is a rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by craniofacial dysmorphism (midface hypoplasia, depressed nasal bridge, small nose with upturned tip, cleft palate, Pierre Robin sequence), bilateral, pronounced sensorineural hearing loss, and skeletal/joint anomalies (including spondyloepiphyseal dysplasia, arthralgia/arthropathy), in the absence of ocular abnormalities.	Genetic otorhinolaryngologic disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:369	Glycogen storage disease due to liver glycogen phosphorylase deficiency	PYGL	1	Liver phosphorylase deficiency, or glycogen storage disease type 6b (Hers' disease, GSD 6b) is a benign and rare form of glycogen storage disease.	Rare genetic hepatic disease;Rare inborn errors of metabolism
Orphanet:166105	FASTKD2-related infantile mitochondrial encephalomyopathy	FASTKD2	1	FASTKD2-related infantile mitochondrial encephalomyopathy is a rare, genetic, mitochondrial oxidative phosphorylation disorder characterized by infantile-onset encephalomyopathy presenting with developmental delay, slowly progressive hemiplegia, intractable epileptic seizures and asymmetrical brain atrophy with dilatation of the ipsilateral ventricle system. Additional features include optic atrophy, mildly increased plasma and/or CSF lactate and decreased cytochrome c oxidase acitivity in skeletal muscle biopsy.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:447	Paroxysmal nocturnal hemoglobinuria	PIGA	1	Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disorder characterized by corpuscular hemolytic anemia, bone marrow failure and frequent thrombotic events.	Rare inborn errors of metabolism;Rare genetic hematologic disease
Orphanet:166108	Intellectual disability, Birk-Barel type	KCNK9	1	Intellectual disability, Birk-Barel type is a rare, genetic, syndromic intellectual disability characterized by congenital central hypotonia, developmental delay, moderate to severe intellectual disability and subtle dysmorphic features which evolve over time (dolichocephaly, myopathic facies, ptosis, short and broad philtrum, tented upper lip vermillion, palatal anomalies, mild micro- and/or retrognathia). Patients present reduced facial movements, lethargy, weak cry, transient neonatal hypoglycemia, severe feeding difficulties and failure to thrive. Dysphagia, particularly of solid food, asthenic body build, joint contractures and scoliosis are additional features.	Rare genetic neurological disorder
Orphanet:166119	Isolated osteopoikilosis	LEMD3	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:166260	Dentinogenesis imperfecta type 2	DSPP	1	Dentinogenesis imperfecta type 2 (DGI-2) is a rare, severe form of dentinogenesis imperfecta (DGI, see this term) and is characterized by weakness and discoloration of all teeth.	Rare genetic odontologic disease
Orphanet:166265	Dentinogenesis imperfecta type 3	DSPP	1	Dentinogenesis imperfecta type 3 (DGI-3) is a rare, severe form of dentinogenesis imperfecta (DGI, see this term) characterized by opalescent primary and permanent teeth, marked attrition, large pulp chambers, multiple pulp exposure and shell teeth radiographically (i.e. teeth which appear hollow due to dentin hypotrophy).	Rare genetic odontologic disease
Orphanet:576	Mucolipidosis type II	GNPTAB	1	Mucolipidosis II (MLII) is a slowly progressive lysosomal disorder characterized by growth retardation, skeletal abnormalities, facial dysmorphism, stiff skin, developmental delay and cardiomegaly.	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:812	Sialidosis type 1	NEU1	1	Sialidosis type 1 (ST-1) is a very rare lysosomal storage disease, and is the normosomatic form of sialidosis (see this term), characterized by gait abnormalities, progressive visual loss, bilateral macular cherry red spots and myoclonic epilepsy and ataxia, that usually presents in the second to third decade of life.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:166282	Familial sick sinus syndrome	SCN5A;HCN4;MYH6	3	Sick sinus syndrome is a rare cardiac rhythm disease, usually of the elderly, characterized by electrocardiographic findings of sinus bradycardia, atrial fibrillation, atrial tachycardia sinus arrest, or sino-atrial block, and that manifest with symptoms like syncope, dizziness, palpitations, fatigue, or even heart failure. It results from malfunction of the cardiac conduction system, probably secondary to degenerative fibrosis of nodal tissue in the elderly or secondary to cardiac disorders in younger patients.	Rare genetic cardiac disease
Orphanet:578	Mucolipidosis type IV	MCOLN1	1	Mucolipidosis type IV (ML IV) is a lysosomal storage disease characterised clinically by psychomotor retardation and visual abnormalities including corneal clouding, retinal degeneration, or strabismus.	Rare genetic eye disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:166286	Porokeratotic eccrine ostial and dermal duct nevus	GJB2	1	NA	Rare genetic tumor
Orphanet:461	Recessive X-linked ichthyosis	STS	1	Recessive X-linked ichthyosis (RXLI) is a genodermatosis belonging to the Mendelian Disorders of Cornification (MeDOC) and characterized by generalized hyperkeratosis and scaling of the skin.	Rare genetic eye disease;Rare genetic skin disease
Orphanet:584	Mucopolysaccharidosis type 7	GUSB	1	A rare, genetic lysosomal storage disease characterized by accumulation of glycosaminoglycans in connective tissue which results in progressive multisystem involvement with severity ranging from mild to severe. The most consistent features include musculoskeletal involvement (particularly dysostosis multiplex, joint restriction, thorax abnormalities, and short stature), limited vocabulary, intellectual disability, coarse facies with a short neck, pulmonary involvement (predominantly decreased pulmonary function), corneal clouding, and cardiac valve disease.	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:166412	Hot water reflex epilepsy	SLC1A1	1	Hot water reflex epilepsy is a rare neurologic disease characterized by the onset of generalized or focal seizures following immersion of the head in hot water, or with hot water being poured over the head. Primary generalized tonic-clonic seizures have been reported in rare cases.	Rare genetic neurological disorder
Orphanet:95	Friedreich ataxia	FXN	1	Friedreich ataxia (FRDA) is an inherited neurodegenerative disorder classically characterized by progressive gait and limb ataxia, dysarthria, dysphagia, oculomotor dysfunction, loss of deep tendon reflexes, pyramidal tract signs, scoliosis, and in some, cardiomyopathy, diabetes mellitus, visual loss and defective hearing.	Rare genetic eye disease;Rare genetic cardiac disease;Rare genetic neurological disorder
Orphanet:586	Cystic fibrosis	CFTR;TGFB1;DCTN4;CLCA4;STX1A	5	Cystic fibrosis (CF) is a genetic disorder characterized by the production of sweat with a high salt content and mucus secretions with an abnormal viscosity.	Rare genetic hepatic disease;Rare genetic gastroenterological disease;Genetic infertility
Orphanet:550	MELAS	MT-TQ;MT-CO1;MT-CO2;MT-CO3;MT-ND1;MT-ND4;MT-ND5;MT-ND6;MT-TL1;MT-TW;MT-TH;MT-TS1;MT-TS2;MT-TF	14	MELAS (Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke) syndrome is a rare progressive multisystemic disorder characterized by encephalomyopathy, lactic acidosis, and stroke-like episodes. Other features include endocrinopathy, heart disease, diabetes, hearing loss, and neurological and psychiatric manifestations.	Genetic otorhinolaryngologic disease;Rare genetic cardiac disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:269	Facioscapulohumeral dystrophy	DUX4;DUX4L1;FRG1;SMCHD1;SMCHD1	5	Facioscapulohumeral muscular dystrophy (FSHD) is characterized by progressive muscle weakness with focal involvement of the facial, shoulder and limb muscles.	Rare genetic neurological disorder
Orphanet:480	Kearns-Sayre syndrome	MT-ATP8;RRM2B;MT-TL1	3	A rare inborn error of metabolism that is characterized by progressive external ophthalmoplegia (PEO), pigmentary retinitis and an onset before the age of 20 years. Common additional features include deafness, cerebellar ataxia and heart block.	Genetic otorhinolaryngologic disease;Rare genetic cardiac disease;Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic endocrine disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:163908	Limbic encephalitis with LGI1 antibodies	HLA-DRB1;HLA-DQB1	2	Limbic encephalitis with LGI1 antibodies is a rare neuroimmunological disorder characterized by the onset of cognitive decline, psychiatric disturbances and seizures (distinctively faciobrachial dystonic seizures) in association with detection of LGI1 antibodies in serum or cerebrospinal fluid. Patients may present with confusion, hallucinations, vocalization, paranoia, tangentiality, aggressive outbursts and/or spatial disorientation, as well as obstinate hyponatremia. It is most often non-paraneoplastic, however comorbid tumors, such as small cell lung cancer and thymoma, have been reported.	
Orphanet:551	MERRF	MT-TP;MT-ND5;MT-TL1;MT-TK;MT-RNR1;MT-TQ;MT-TH;MT-TS1;MT-TS2;MT-TF	10	MERRF (Myoclonic Epilepsy with Ragged Red Fibers) syndrome is a mitochondrial encephalomyopathy characterized by myoclonic seizures.	Rare genetic cardiac disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:597	Central core disease	RYR1	1	Central core disease (CCD) is an inherited neuromuscular disorder characterised by central cores on muscle biopsy and clinical features of a congenital myopathy.	Rare genetic neurological disorder
Orphanet:163746	Peripheral demyelinating neuropathy-central dysmyelinating leukodystrophy-Waardenburg syndrome-Hirschsprung disease	SOX10	1	Peripheral demyelinating neuropathy-central dysmyelinating leukodystrophy-Waardenburg syndrome-Hirschsprung disease (PCWH) is a systemic disease characterized by the association of the features of Waardenburg-Shah syndrome (WSS) with neurological features of variable severity.	Genetic otorhinolaryngologic disease;Rare genetic gastroenterological disease;Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare genetic skin disease
Orphanet:684	Paramyotonia congenita of Von Eulenburg	SCN4A	1	Paramyotonia congenita of Von Eulenburg is characterised by exercise- or cold-induced myotonia and muscle weakness. Prevalence is unknown. The syndrome is nonprogressive and is transmitted as an autosomal dominant trait. It is caused by mutations in the gene encoding the alpha subunit of the type IV voltage-gated sodium channel (SCN4A; 17q23.3).	Rare genetic neurological disorder
Orphanet:163931	Acrodermatitis continua of Hallopeau	IL36RN;AP1S3	2	A rare, genetic, chronic, recurrent, slowly progressive, epidermal disease characterized by small, sterile, pustular eruptions, involving the nails and surrounding skin of the fingers and/or toes, which coalesce and burst, leaving erythematous, atrophic skin where new pustules develop. Onychodystrophy is frequently associated and anonychia and osteolysis are reported in severe cases. Local expansion (to involve the hands, forearms and/or feet) and involvement of mucosal surfaces (e.g. conjunctiva, tongue, urethra) may be observed.	Rare genetic skin disease
Orphanet:163927	Pustulosis palmaris et plantaris	IL36RN;AP1S3	2	NA	Rare genetic skin disease
Orphanet:273	Steinert myotonic dystrophy	DMPK	1	Steinert disease, also known as myotonic dystrophy type 1, is a muscle disease characterized by myotonia and by multiorgan damage that combines various degrees of muscle weakness, arrhythmia and/or cardiac conduction disorders, cataract, endocrine damage, sleep disorders and baldness.	Rare genetic cardiac disease;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease;Genetic infertility;Rare genetic neurological disorder
Orphanet:163937	X-linked intellectual disability, Najm type	CASK	1	Najm type X-linked intellectual deficit is a rare cerebellar dysgenesis syndrome characterized by variable clinical manifestations ranging from mild intellectual deficit with or without congenital nystagmus, to severe cognitive impairment associated with cerebellar and pontine hypoplasia/atrophy and abnormalities of cortical development.	Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:614	Thomsen and Becker disease	CLCN1	1	A rare, genetic, skeletal muscle channelopathy characterized by slow muscle relaxation after contraction (myotonia).	Rare genetic neurological disorder
Orphanet:163966	X-linked dominant chondrodysplasia, Chassaing-Lacombe type	HDAC6	1	X-linked dominant chondrodysplasia Chassaing-Lacombe type is a rare genetic bone disorder characterized by chondrodysplasia, intrauterine growth retardation (IUGR), hydrocephaly and facial dysmorphism in the affected males.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:163956	X-linked intellectual disability, Nascimento type	UBE2A	1	X-linked intellectual disability, Nascimento type is a rare X-linked intellectual disability syndrome characterized by intellectual disability (with severe speech impairment), a myxedematous appearance, dysmorphic facial features (including large head, synophrys, prominent supraorbital ridges, almond-shaped and deep-set eyes, large ears, wide mouth with everted lower lip and downturned lip corners), low posterior hairline, short, broad neck, marked general hirsutism and abnormal hair whorls, skin changes (e.g. dry skin or hypopigmented spots), widely spaced nipples, obesity, micropenis, onychodystrophy and seizures.	Rare genetic neurological disorder
Orphanet:324	Fabry disease	GLA	1	Fabry disease (FD) is a progressive, inherited, multisystemic lysosomal storage disease characterized by specific neurological, cutaneous, renal, cardiovascular, cochleo-vestibular and cerebrovascular manifestations.	Rare genetic skin disease;Rare genetic neurological disorder;Rare genetic cardiac disease;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare inborn errors of metabolism;Rare genetic renal disease
Orphanet:163985	Hyperekplexia-epilepsy syndrome	ARHGEF9	1	A rare, X-linked, syndromic intellectual disability disease characterized by neonatal hypertonia which evolves to hypotonia and an exaggerated startle response (to sudden visual, auditory or tactile stimuli), followed by the development of early-onset, frequently refractory, tonic or myoclonic seizures. Progressive epileptic encephalopathy, intellectual disability, and psychomotor development arrest, with subsecuent decline, may be additionally associated.	Rare genetic neurological disorder
Orphanet:163988	OBSOLETE: Developmental delay-deafness syndrome, Hildebrand type	POU3F4	1	NA	NA
Orphanet:778	Rett syndrome	MECP2	1	Rett syndrome (RTT) is a severe neurodevelopmental disorder affecting the central nervous system.	Rare genetic neurological disorder
Orphanet:307	Juvenile myoclonic epilepsy	ICK;CACNB4;EFHC1;GABRA1;GABRD;KCNQ3;JRK;CLCN2	8	Juvenile myoclonic epilepsy is the most common hereditary idiopathic generalized epilepsy syndrome and is characterized by myoclonic jerks of the upper limbs on awakening, generalized tonic-clonic seizures manifesting during adolescence and triggered by sleep deprivation, alcohol intake, and cognitive activities, and typical absence seizures (30% of cases).	Rare genetic neurological disorder
Orphanet:1941	Juvenile absence epilepsy	EFHC1	1	Juvenile absence epilepsy (JAE) is a genetic epilepsy with onset occurring around puberty. JAE is characterized by sporadic occurrence of absence seizures, frequently associated with a long-life prevalence of generalized tonic-clonic seizures (GTCS) and sporadic myoclonic jerks.	Rare genetic neurological disorder
Orphanet:892	Von Hippel-Lindau disease	VHL	1	Von Hippel-Lindau disease (VHL) is a familial cancer predisposition syndrome associated with a variety of malignant and benign neoplasms, most frequently retinal, cerebellar, and spinal hemangioblastoma, renal cell carcinoma (RCC), and pheochromocytoma.	Inherited cancer-predisposing syndrome;Rare genetic renal disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic endocrine disease;Rare genetic tumor
Orphanet:164736	Familial advanced sleep-phase syndrome	PER3;CSNK1D;PER2	3	Familial advanced sleep-phase syndrome (FASPS) is a very rare circadian rhythm sleep disorder characterized by very early sleep onset and offset possibly resulting in emotional and physical disruptions.	
Orphanet:731	Autosomal recessive polycystic kidney disease	DZIP1L;PKHD1	2	A rare, genetic hepatorenal fibrocystic syndrome characterized by cystic dilatation and ectasia of renal collecting tubules, and a ductal plate malformation of the liver resulting in congenital hepatic fibrosis. Clinical presentation, whilst typically in utero or at birth, is variable and in the most severe cases includes Potter-sequence, oligohydramnios, pulmonary hypoplasia, and massively enlarged echogenic kidneys.	Rare genetic renal disease;Genetic infertility;Rare genetic hepatic disease
Orphanet:138	CHARGE syndrome	SEMA3E;CHD7	2	CHARGE syndrome is a multiple congenital anomaly syndrome characterized by the variable combination of multiple anomalies, mainly Coloboma; Choanal atresia/stenosis; Cranial nerve dysfunction; Characteristic ear anomalies (known as the major 4 C's).	Genetic otorhinolaryngologic disease;Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility;Rare genetic urogenital disease;Rare genetic eye disease;Rare genetic immune disease;Rare genetic cardiac disease
Orphanet:165805	Familial mesial temporal lobe epilepsy with febrile seizures	CPA6	1	A rare, genetic, familial partial epilepsy disease characterized by simple partial seizures, complex partial seizures and/or secondarily generalized seizures, originating from the inner aspect of the temporal lobe, associated with an antecedant history of febrile seizures, ocurring in various members of a family. Hippocampal abnormalities (e.g. hippocampal sclerosis) may also be associated.	Rare genetic neurological disorder
Orphanet:803	Amyotrophic lateral sclerosis	CCNF;TAF15;EPHA4;ANXA11;C21ORF2;GLE1;NEK1;CHCHD10;DAO;ATXN2;CHMP2B;SOD1;TREM2;VAPB;VCP;NEFH;OPTN;DCTN1;TARDBP;FIG4;FUS;ANG;MATR3;PRPH;PON1;PON2;PON3;SQSTM1;UBQLN2;C9ORF72;PFN1;TBK1;HNRNPA1;PPARGC1A;ERBB4;UNC13A	36	A neurodegenerative disease characterized by progressive muscular paralysis reflecting degeneration of motor neurons in the primary motor cortex, corticospinal tracts, brainstem and spinal cord.	
Orphanet:100	Ataxia-telangiectasia	ATM	1	A rare disorder characterized by the association of severe combined immunodeficiency (affecting mainly the humoral immune response) with progressive cerebellar ataxia. It is characterized by neurological signs, telangiectasia, increased susceptibility to infections and a higher risk of cancer.	Rare genetic skin disease;Inherited cancer-predisposing syndrome;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Rare genetic immune disease
Orphanet:399	Huntington disease	HTT;SLC2A3	2	Huntington disease (HD) is a rare neurodegenerative disorder of the central nervous system characterized by unwanted choreatic movements, behavioral and psychiatric disturbances and dementia.	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:501	Lafora disease	EPM2A;NHLRC1	2	Lafora disease (LD) is a rare, inherited, severe, progressive myoclonic epilepsy characterized by myoclonus and/or generalized seizures, visual hallucinations (partial occipital seizures), and progressive neurological decline.	Rare genetic neurological disorder
Orphanet:166011	Multiple epiphyseal dysplasia, Beighton type	COL2A1	1	Multiple epiphyseal dysplasia, Beighton type is a skeletal dysplasia characterized by epiphyseal dysplasia (usually mild) associated with progressive myopia, retinal thinning, crenated cataracts, conductive deafness, and stubby digits.	Rare genetic bone disease;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:567	22q11.2 deletion syndrome	TBX1;TBX1;ARVCF;GP1BB;UFD1;COMT;HIRA;JMJD1C;RREB1;SEC24C	10	22q11.2 deletion syndrome (DS) is a chromosomal anomaly which causes a congenital malformation disorder whose common features include cardiac defects, palatal anomalies, facial dysmorphism, developmental delay and immune deficiency.	Genetic otorhinolaryngologic disease;Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Rare genetic immune disease;Rare genetic cardiac disease;Rare chromosomal anomaly;Rare genetic endocrine disease
Orphanet:232	Sickle cell anemia	HBB	1	Sickle cell anemias are chronic hemolytic diseases that may induce three types of acute accidents: severe anemia, severe bacterial infections, and ischemic vasoocclusive accidents (VOA) caused by sickle-shaped red blood cells obstructing small blood vessels and capillaries. Many diverse complications can occur.	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility;Rare genetic hematologic disease;Rare genetic renal disease;Rare genetic neurological disorder;Rare genetic bone disease
Orphanet:165994	Pituitary resistance to thyroid hormone	THRB	1	NA	NA
Orphanet:536	Systemic lupus erythematosus	PXK;CTLA4;TREX1;HLA-DRB1;IL10;MECP2;FCGR3B;C4A;C4B;CR2;BLK;IRF5;PDCD1;PTPN22;STAT4;FCGR2B;DNASE1;BANK1;ITGAM;KIAA0319L;JAZF1;TNIP1;TNFAIP3;UBE2L3;TNFSF4;SPP1;IRAK1;ETS1	28	NA	
Orphanet:166002	Multiple epiphyseal dysplasia due to collagen 9 anomaly	COL9A1;COL9A2;COL9A3	3	Multiple epiphyseal dysplasia due to collagen 9 anomaly is a rare primary bone dysplasia disorder characterized by normal or mild short stature, early-onset pain and/or stiffness of the joints (mainly affecting knees but also elbows, wrists, ankles and fingers, with relative sparing of the hips) and early degenerative joint disease. Other skeletal anomalies (incl. varus or valgus deformities, osteochondritis dissecans, abnormal carpal shape, free articular bodies) and mild myopathy have also been reported.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:534	Oculocerebrorenal syndrome of Lowe	OCRL	1	Oculocerebrorenal syndrome of Lowe (OCRL) is a multisystem disorder characterized by congenital cataracts, glaucoma, intellectual disabilities, postnatal growth retardation and renal tubular dysfunction with chronic renal failure.	Rare inborn errors of metabolism;Rare genetic renal disease;Ciliopathy;Rare genetic eye disease;Rare genetic neurological disorder
Orphanet:165991	Exercise-induced hyperinsulinism	SLC16A1	1	Exercise-induced hyperinsulinism (EIHI) is a form of diazoxide-sensitive diffuse hyperinsulinism (DHI) characterized by episodes of hypoglycemia induced by exercise due to an inappropriate lactate and pyruvate sensitivity in pancreatic beta-cells.	Rare inborn errors of metabolism;Rare genetic endocrine disease;Rare genetic developmental defect during embryogenesis
Orphanet:652	Multiple endocrine neoplasia type 1	MEN1;CDKN1B;CDKN1A;CDKN2B;CDKN2C	5	Multiple endocrine neoplasia Type 1 (MEN1) is a frequent form of MEN (see this term), a rare inherited cancer syndrome, characterized by the development of neuroendocrine tumors of the parathyroid, pancreas, and anterior pituitary gland, and less commonly the adrenal cortical gland, with other non-endocrine tumors in some patients.	Inherited cancer-predisposing syndrome;Rare genetic endocrine disease;Rare genetic tumor
Orphanet:908	Fragile X syndrome	FMR1	1	Fragile X syndrome (FXS) is a rare genetic disease associated with mild to severe intellectual deficit that may be associated with behavioral disorders and characteristic physical features.	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic endocrine disease;Rare genetic neurological disorder
Orphanet:47	X-linked agammaglobulinemia	BTK	1	A clinically variable form of isolated agammaglobulinemia, an inherited immunodeficiency disorder, characterized in affected males by recurrent bacterial infections during infancy.	Rare genetic immune disease
Orphanet:905	Wilson disease	ATP7B	1	Wilson disease is a very rare inherited multisystemic disease presenting non-specific neurological, hepatic, psychiatric or osseo-muscular manifestations due to excessive copper deposition in the body.	Rare genetic neurological disorder;Rare genetic hepatic disease;Rare inborn errors of metabolism;Rare genetic renal disease;Rare genetic eye disease
Orphanet:792	X-linked retinoschisis	RS1	1	X-linked retinoschisis (XLRS) is a genetic ocular disease that is characterized by reduced visual acuity in males due to juvenile macular degeneration.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:383	X-linked mixed deafness with perilymphatic gusher	POU3F4	1	NA	NA
Orphanet:827	Stargardt disease	CNGB3;PRPH2;ABCA4;ELOVL4;PROM1	5	Stargardt disease, also known as Stargardt 1 (STGD1), is an autosomal recessive form of retinal dystrophy that is usually characterized by a progressive loss of central vision associated with irregular macular and perimacular yellow-white fundus flecks, and a so-called ''beaten bronze'' atrophic central macular lesion.	Rare genetic eye disease
Orphanet:906	Wiskott-Aldrich syndrome	WAS;WIPF1	2	A primary immunodeficiency disease characterized by microthrombocytopenia, eczema, infections and an increased risk for autoimmune manifestations and malignancies.	Inherited cancer-predisposing syndrome;Rare genetic immune disease;Rare genetic hematologic disease;Rare genetic skin disease
Orphanet:904	Williams syndrome	RFC2;BAZ1B;TBL2;CLIP2;ELN;GTF2I;GTF2IRD1;LIMK1	8	A rare genetic multisystemic neurodevelopmental disorder characterized by a distinct facial appearance, cardiac anomalies (most frequently supravalvular aortic stenosis), cognitive and developmental abnormalities, and connective tissue abnormalities (such as joint laxity).	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic cardiac disease;Rare genetic renal disease;Rare genetic eye disease;Rare chromosomal anomaly
Orphanet:280	Wolf-Hirschhorn syndrome	NSD2;NELFA;LETM1	3	A developmental disorder characterized by typical craniofacial features, prenatal and postnatal growth impairment, intellectual disability, severe delayed psychomotor development, seizures, and hypotonia.	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare chromosomal anomaly
Orphanet:15	Achondroplasia	FGFR3	1	A primary bone dysplasia with micromelia characterized by rhizomelia, exaggerated lumbar lordosis, brachydactyly, and macrocephaly with frontal bossing and midface hypoplasia.	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:96	Ataxia with vitamin E deficiency	TTPA	1	A neurodegenerative disease belonging to the inherited cerebellar ataxias mainly characterized by progressive spino-cerebellar ataxia, loss of proprioception, areflexia, and is associated with a marked deficiency in vitamin E.	Rare genetic neurological disorder;Rare genetic eye disease;Rare inborn errors of metabolism
Orphanet:101	Dentatorubral pallidoluysian atrophy	ATN1	1	A rare subtype of autosomal dominant cerebellar ataxia type I characterized by involuntary movements, ataxia, epilepsy, mental disorders, cognitive decline and prominent anticipation.	Rare genetic neurological disorder
Orphanet:276	T-B+ severe combined immunodeficiency due to gamma chain deficiency	IL2RG	1	Severe combined immunodeficiency (SCID) due to gamma chain deficiency, also called SCID-X1, is a form of SCID (see this term) characterized by severe and recurrent infections, associated with diarrhea and failure to thrive.	Rare genetic immune disease
Orphanet:481	Kennedy disease	AR	1	Kennedy's disease, also known as bulbospinal muscular atrophy (BSMA), is a rare X-linked recessive motor neuron disease characterized by proximal and bulbar muscle wasting.	Rare genetic neurological disorder;Genetic infertility
Orphanet:664	Ornithine transcarbamylase deficiency	OTC	1	A rare, genetic disorder of urea cycle metabolism and ammonia detoxification characterized by either a severe, neonatal-onset disease found mainly in males, or later-onset (partial) forms of the disease. Both present with episodes of hyperammonemia that can be fatal and which can lead to neurological sequelae.	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:394	Classic homocystinuria	CBS	1	Classical homocystinuria due to cystathionine beta-synthase (CbS) deficiency is characterized by the multiple involvement of the eye, skeleton, central nervous system, and vascular system.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:508	Leprechaunism	INSR	1	Leprechaunism is a congenital form of extreme insulin resistance (a group of syndromes that also includes Rabson-Mensenhall syndrome, type A insulin-resistance syndrome, and acquired type B insulin-resistance syndrome; see these terms) characterized by intrauterine and mainly postnatal severe growth retardation.	Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease;Rare genetic skin disease
Orphanet:163596	Hb Bart's hydrops fetalis	HBA2;HBA1	2	A rare, severe form of alpha-thalassemia that is almost always lethal. It is characterized by fetal onset of generalized edema, pleural and pericardial effusions, and severe hypochromic anemia.	Rare genetic hematologic disease;Rare genetic renal disease
Orphanet:429	Hypochondroplasia	FGFR3	1	Hypochondroplasia is characterized by disproportionate short stature, mild lumbar lordosis and limited extension of the elbow joints.	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:104	Leber hereditary optic neuropathy	NDUFS2;MT-ATP6;MT-CO1;MT-CO3;MT-CYB;MT-ND1;MT-ND2;MT-ND4;MT-ND4L;MT-ND5;MT-ND6	11	Leber's hereditary optic neuropathy (LHON) is a mitochondrial neurodegenerative disease affecting the optic nerve and often characterized by sudden vision loss in young adult carriers.	Rare genetic cardiac disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:163634	Maffucci syndrome	IDH2;IDH1	2	Maffucci syndrome is a very rare genetic bone and skin disorder characterized by multiple enchondromas, leading to bone deformities, combined with multiple dark, irregularly shaped hemangiomas or less commonly lymphangiomas.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic bone disease;Rare genetic tumor
Orphanet:2182	Hydrocephalus with stenosis of the aqueduct of Sylvius	L1CAM	1	Hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS) is a historical term used to describe a phenotype now considered to be part of the X-linked L1 clinical spectrum (L1 syndrome, see this term). HSAS is characterized by severe hydrocephalus mostly with prenatal onset, signs of intracranial hypertension, adducted thumbs, spasticity, and severe intellectual deficit. HSAS represents the severe end of the spectrum and is associated with poor prognosis.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:163717	Benign familial mesial temporal lobe epilepsy	CPA6	1	Benign familial mesial temporal lobe epilepsy is a rare epilepsy characterized by seizures with viscerosensory or experential auras, onset in adolescence or early adulthood and good prognosis. It is defined as at least 24 months of seizure freedom with or without antiepileptic medication.	Rare genetic neurological disorder
Orphanet:649	Norrie disease	NDP	1	Norrie disease (ND) is a rare X-linked genetic vitreoretinal condition characterized by abnormal retinal development with congenital blindness. Common associated manifestations include sensorineural hearing loss and developmental delay, intellectual disability and/or behavioral disorders.	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:163721	Rolandic epilepsy-speech dyspraxia syndrome	SRPX2;GRIN2A	2	Rolandic epilepsy-speech dyspraxia syndrome is a rare, genetic epilepsy characterized by speech disorder (including a range of symptoms from dysarthria, speech dyspraxia, receptive and expressive language delay/regression and acquired aphasia to subtle impairments of conversational speech) and epilepsy (mostly focal and secondary generalized childhood-onset seizures, sometimes with aura). Mild to severe intellectual disability may also be observed.	Rare genetic neurological disorder
Orphanet:163684	Leukoencephalopathy-dystonia-motor neuropathy syndrome	SCP2	1	Leukoencephalopathy-dystonia-motor neuropathy syndrome is a peroxisomal neurodegenerative disorder characterized by spasmodic torticollis, dystonic head tremor, intention tremor, nystagmus, hyposmia, and hypergonadotrophic hypogonadism with azoospermia. Slight cerebellar signs (left-sided intention tremor, balance and gait impairment) are also noted. Magnetic resonance imaging (MRI) shows bilateral hyperintense signals in the thalamus, butterfly-like lesions in the pons, and lesions in the occipital region, whereas nerve conduction studies of the lower extremities shows a predominantly motor and slight sensory neuropathy.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:163681	Cortical dysplasia-focal epilepsy syndrome	CNTNAP2	1	A rare genetic epilepsy characterized by relatively large head circumference or macrocephaly, diminished or absent deep-tendon reflexes and mild gross motor delay in infancy, followed by intractable focal seizures with language regression, behavioral abnormalities (hyperactivity, attention deficit, aggressive/autoaggressive behavior, autistic features) and intellectual disability later in life.	Rare genetic neurological disorder
Orphanet:379	Chronic granulomatous disease	CYBB;NCF1;NCF2;CYBA;NCF4	5	Chronic granulomatous disease (CGD) is a rare primary immunodeficiency, mainly affecting phagocytes, which is characterized by an increased susceptibility to severe and recurrent bacterial and fungal infections, along with the development of granulomas.	Rare genetic skin disease;Rare genetic immune disease;Rare genetic eye disease
Orphanet:16	Blue cone monochromatism	OPN1MW;OPN1LW	2	Blue cone monochromatism (BCM) is a recessive X-linked disease characterized by severely impaired color discrimination, low visual acuity, nystagmus, and photophobia, due to dysfunction of the red (L) and green (M) cone photoreceptors. BCM is as an incomplete form of achromatopsia (see this term).	Rare genetic eye disease
Orphanet:644	NARP syndrome	MT-ATP6	1	Neuropathy, Ataxia, and Retinitis Pigmentosa (NARP) syndrome is a clinically heterogeneous progressive condition characterized by a combination of proximal neurogenic muscle weakness, sensory-motor neuropathy, ataxia, and pigmentary retinopathy.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic eye disease;Rare genetic neurological disorder
Orphanet:163699	Alveolar soft tissue sarcoma	TFE3;ASPSCR1	2	NA	
Orphanet:637	Neurofibromatosis type 2	NF2	1	Neurofibromatosis type 2 (NF2) is a tumor-prone disorder characterized by the development of multiple schwannomas and meningiomas.	Genetic otorhinolaryngologic disease;Rare genetic eye disease
Orphanet:163696	Action myoclonus-renal failure syndrome	SCARB2	1	A rare epilepsy syndrome characterized by progressive myoclonus epilepsy in association with primary glomerular disease. Patients present with neurologic symptoms (including tremor, action myoclonus, tonic-clonic seizures, later ataxia and dysarthria) that may precede, occur simultaneously or be followed by renal manifestations including proteinuria that progresses to nephrotic syndrome and end-stage renal disease. In some patients, sensorimotor peripheral neuropathy, sensorineural hearing loss and dilated cardiomyopathy are associated symptoms.	Rare genetic renal disease;Rare genetic neurological disorder
Orphanet:181	X-linked hypohidrotic ectodermal dysplasia	EDA;EDA2R	2	NA	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:163693	2p21 microdeletion syndrome	SLC3A1;PREPL;CAMKMT;PPM1B	4	The 2p21 microdeletion syndrome consists of cystinuria, neonatal seizures, hypotonia, severe growthand developmental delay, facial dysmorphism, and lactic acidemia.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare chromosomal anomaly;Rare genetic renal disease
Orphanet:163690	Hypotonia-cystinuria syndrome	SLC3A1;PREPL	2	Hypotonia-Cystinuria syndrome (HCS) is a rare syndrome including neonatal and infantile hypotonia and failure to thrive, cystinuria type 1 and nephrolithiasis, growth retardation due to growth hormone deficiency, and minor facial dysmorphism.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare chromosomal anomaly;Rare genetic renal disease
Orphanet:337	Fibrodysplasia ossificans progressiva	ACVR1	1	Fibrodysplasia ossificans progressiva (FOP) is a severely disabling heritable disorder of connective tissue characterized by congenital malformations of the great toes and progressive heterotopic ossification that forms qualitatively normal bone in characteristic extraskeletal sites.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic skin disease
Orphanet:377	Gorlin syndrome	PTCH1;SUFU;PTCH2	3	A rare hereditary disorder due to autosomal dominant transmission with hamartosis characterized by multiple early-onset basal cell carcinoma (BCC), multiple jaw keratocysts and skeletal abnormalities.	Rare genetic tumor;Rare genetic developmental defect during embryogenesis
Orphanet:648	Noonan syndrome	RRAS;PTPN11;BRAF;SOS1;KRAS;RAF1;NRAS;KAT6B;RIT1;LZTR1;A2ML1;RASA2;SOS2	13	Noonan Syndrome (NS) is characterised by short stature, typical facial dysmorphism and congenital heart defects.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Inherited cancer-predisposing syndrome;Rare genetic cardiac disease;Rare genetic eye disease;Rare genetic skin disease;Rare genetic neurological disorder;Rare genetic endocrine disease;Genetic infertility;RASopathy
Orphanet:281	Monosomy 5p	SEMA5A;CTNND2	2	Monosomy 5p, also known as Cri du chat syndrome, is a rare autosomal deletion syndrome characterized by a mewing cry (cri du chat) in infancy, multiple congenital anomalies, intellectual disability, microcephaly, and facial dysmorphism.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare chromosomal anomaly
Orphanet:752	46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency	HSD17B3	1	17-beta-hydroxysteroid dehydrogenase isozyme 3 (17betaHSD III) deficiency is a rare disorder leading to male pseudohermaphroditism (MPH), a condition characterized by incomplete differentiation of the male genitalia in 46X,Y males.	Genetic infertility;Rare genetic gynecological and obstetrical diseases;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease
Orphanet:510	Lesch-Nyhan syndrome	HPRT1	1	Lesch-Nyhan syndrome (LNS) is the most severe form of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency (see this term), a hereditary disorder of purine metabolism, and is associated with uric acid overproduction (UAO), neurological troubles, and behavioral problems.	Rare inborn errors of metabolism;Rare genetic neurological disorder;Rare genetic hematologic disease;Rare genetic renal disease
Orphanet:524	Li-Fraumeni syndrome	CDKN2A;TP53;MDM2;CHEK2	4	Li-Fraumeni syndrome (LFS) is a rare cancer predisposition syndrome characterized by the early-onset of multiple primary cancers such as breast cancer, soft tissue and bone sarcomas (see these terms), brain tumors and adrenal cortical carcinoma (ACC) (see this term).	
Orphanet:640	Hereditary neuropathy with liability to pressure palsies	PMP22;PMP22	2	Hereditary neuropathy with liability to pressure palsies (HNPP) is an inherited peripheral nerve disorder characterized by recurrent mononeuropathy usually triggered by minor physical activities.	Rare chromosomal anomaly;Rare genetic neurological disorder
Orphanet:60	Alpha-1-antitrypsin deficiency	SERPINA1	1	A hereditary disease that develops in adulthood and is characterized by chronic liver disorders (cirrhosis), respiratory disorders (emphysema), and rarely panniculitis.	Rare genetic hepatic disease;Rare inborn errors of metabolism;Rare genetic renal disease;Serpinopathy
Orphanet:895	Waardenburg syndrome type 2	KITLG;SNAI2;SOX10;MITF;EDNRB	5	An autosomal dominant subtype of Waardenburg syndrome (WS) characterized by varying degrees of deafness and pigmentation anomalies of eyes, hair and skin, but without dystopia canthorum.	Genetic otorhinolaryngologic disease;Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:896	Waardenburg syndrome type 3	PAX3	1	A very rare subtype of Waardenburg syndrome (WS) that is characterized by limb anomalies in association with congenital hearing loss, minor defects in structures arising from neural crest, resulting in pigmentation anomalies of eyes, hair, and skin.	Genetic otorhinolaryngologic disease;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic skin disease
Orphanet:857	Townes-Brocks syndrome	SALL1;DACT1	2	A rare genetic disorder characterized by the triad of imperforate anus, dysplastic ears often associated with sensorineural and/or conductive hearing impairment, and thumb malformations. These features are often associated with other signs mainly affecting the kidneys and heart.	Genetic otorhinolaryngologic disease;Rare genetic developmental defect during embryogenesis;Rare genetic renal disease;Rare genetic bone disease
Orphanet:894	Waardenburg syndrome type 1	PAX3	1	A subtype of Waardenburg syndrome (WS) characterized by congenital deafness, minor defects in structures arising from neural crest resulting in pigmentation anomalies of eyes, hair, and skin, in combination with dystopia canthorum.	Genetic otorhinolaryngologic disease;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic skin disease
Orphanet:682	Hyperkalemic periodic paralysis	SCN4A	1	A rare muscle disorder characterized by episodic attacks of muscle weakness associated with an increase in serum potassium concentration.	Rare genetic neurological disorder
Orphanet:800	Schwartz-Jampel syndrome	HSPG2	1	A rare syndrome characterised by myotonia and osteoarticular abnormalities.	Rare genetic bone disease;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:628	Diastrophic dwarfism	SLC26A2	1	A rare disorder marked by short stature with short extremities (final adult height is 120cm +/- 10cm), and joint malformations leading to multiple joint contractures (principally involving the shoulders, elbows, interphalangeal joints and hips).	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:681	Hypokalemic periodic paralysis	SCN4A;CACNA1S;KCNE3	3	A rare disorder characterised by episodes of muscle paralysis lasting from a few to 24-48 hours and associated with a fall in blood potassium levels.	Rare genetic neurological disorder
Orphanet:107	BOR syndrome	SIX1;EYA1;SIX5	3	Branchiootorenal (BOR) syndrome is characterized by branchial arch anomalies (branchial clefts, fistulae, cysts), hearing impairment (malformations of the auricle with pre-auricular pits, conductive or sensorineural hearing impairment), and renal malformations (urinary tree malformation, renal hypoplasia or agenesis, renal dysplasia, renal cysts).	Genetic otorhinolaryngologic disease;Rare genetic developmental defect during embryogenesis;Rare genetic renal disease;Rare genetic bone disease
Orphanet:774	Hereditary hemorrhagic telangiectasia	ACVRL1;SMAD4;ENG;GDF2	4	An inherited disorder of angiogenesis characterized by mucocutaneous telangiectases and visceral arteriovenous malformations.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:794	Saethre-Chotzen syndrome	FGFR3;FGFR2;TWIST1	3	Saethre-Chotzen syndrome (SCS) is an inherited craniosynostosis syndrome characterized by unilateral or bilateral coronal synostosis, facial asymmetry, ptosis, strabismus and small ears with prominent crus, among other less common manifestations.	Inherited cancer-predisposing syndrome;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2869	Peutz-Jeghers syndrome	STK11	1	An inherited gastrointestinal disorder characterized by development of characteristic hamartomatous polyps throughout the gastrointestinal (GI) tract, and by mucocutaneous pigmentation. This disorder carries a considerably increased risk of GI and extra-GI malignancies.	Rare genetic gastroenterological disease;Inherited cancer-predisposing syndrome;Rare genetic tumor;Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:893	WAGR syndrome	BDNF;WT1;PAX6	3	A rare genetic disorder characterized by an unusual complex of congenital developmental abnormalities with intellectual disability, and an increased risk of developing Wilms tumor.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Inherited cancer-predisposing syndrome;Rare genetic endocrine disease;Rare genetic gynecological and obstetrical diseases;Rare genetic urogenital disease;Rare genetic eye disease;Rare chromosomal anomaly
Orphanet:912	Zellweger syndrome	PEX11B;PEX2;PEX1;PEX10;PEX12;PEX13;PEX14;PEX16;PEX19;PEX26;PEX3;PEX5;PEX6	13	A rare peroxisome biogenesis disorder (the most severe variant of Peroxisome biogenesis disorder spectrum) characterized by neuronal migration defects in the brain, dysmorphic craniofacial features, profound hypotonia, neonatal seizures, and liver dysfunction.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic hepatic disease;Rare inborn errors of metabolism;Rare genetic renal disease
Orphanet:53	Albers-Schönberg osteopetrosis	CLCN7	1	A sclerosing disorder of the skeleton characterized by increased bone density that classically displays the radiographic sign of ''sandwich vertebrae'' (dense bands of sclerosis parallel to the vertebral endplates).	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease
Orphanet:14	Abetalipoproteinemia	MTTP	1	A severe, familial hypobetalipoproteinemia characterized by permanently low levels (below the 5th percentile) of apolipoprotein B and LDL cholesterol, and by growth delay, malabsorption, hepatomegaly, and neurological and neuromuscular manifestations.	Rare genetic neurological disorder;Rare genetic eye disease;Rare inborn errors of metabolism;Rare genetic endocrine disease;Rare genetic gastroenterological disease;Rare genetic hematologic disease
Orphanet:167	Chédiak-Higashi syndrome	LYST	1	Chédiak-Higashi syndrome (CHS) is a rare severe genetic disorder generally characterized by partial oculocutaneous albinism (OCA, see this term), severe immunodeficiency, mild bleeding, neurological dysfunction and lymphoproliferative disorder. A classic, early-onset form and an attenuated, later-onset form (Atypical CHS; see this term) have been described.	Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic eye disease;Rare genetic skin disease;Rare genetic hematologic disease;Rare genetic immune disease
Orphanet:207	Crouzon disease	FGFR2;ERF	2	Crouzon disease is characterized by craniosynostosis and facial hypoplasia.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease
Orphanet:201	Cowden syndrome	PTEN;PIK3CA;SDHB;SDHD;SDHC;SEC23B;AKT1;KLLN	8	 mutations, it belongs to the PTEN hamartoma tumor syndrome (PHTS; see this term) group.	Inherited cancer-predisposing syndrome;Rare genetic developmental defect during embryogenesis;Rare genetic tumor
Orphanet:192	Coffin-Lowry syndrome	RPS6KA3	1	Coffin-Lowry syndrome (CLS) is a rare genetic neurological disorder characterized by psychomotor and growth retardation, facial dysmorphism, digit abnormalities, and progressive skeletal changes.	Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease;Rare genetic neurological disorder
Orphanet:2442	X-linked lymphoproliferative disease	SH2D1A;XIAP	2	NA	NA
Orphanet:169808	Mild hemophilia A	F8	1	Mild hemophilia A is a form of hemophilia A (see this term) characterized by a small deficiency of factor VIII leading to abnormal bleeding as a result of minor injuries, or following surgery or tooth extraction.	Rare genetic hematologic disease
Orphanet:169802	Severe hemophilia A	F8	1	Severe hemophilia A is a form of hemophilia A (see this term) characterized by a large deficiency of factor VIII leading to frequent spontaneous hemorrhage and abnormal bleeding as a result of minor injuries, or following surgery or tooth extraction.	Rare genetic hematologic disease
Orphanet:169805	Moderately severe hemophilia A	F8	1	Moderately severe hemophilia A is a form of hemophilia A (see this term) characterized by factor VIII deficiency leading to abnormal bleeding as a result of minor injuries, or following surgery or tooth extraction.	Rare genetic hematologic disease
Orphanet:562	McCune-Albright syndrome	GNAS	1	McCune-Albright syndrome (MAS) is classically defined by the clinical triad of fibrous dysplasia of bone (FD), café-au-lait skin spots, and precocious puberty (PP).	Inherited cancer-predisposing syndrome;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic skin disease;Rare genetic endocrine disease;Rare genetic gynecological and obstetrical diseases
Orphanet:565	Menkes disease	ATP7A	1	Menkes disease (MD) is a usually severe multisystemic disorder of copper metabolism, characterized by progressive neurodegeneration and marked connective tissue anomalies as well as typical sparse abnormal steely hair.	Rare genetic skin disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:474	Jeune syndrome	DYNC2LI1;IFT80;DYNC2H1;TTC21B;WDR19;IFT140;WDR60;IFT172;WDR34;CEP120	10	"Jeune syndrome, also called asphyxiating thoracic dystrophy, is a short-rib dysplasia characterized by a narrow thorax, short limbs and radiological skeletal abnormalities including ""trident"" aspect of the acetabula and metaphyseal changes."	Rare genetic renal disease;Ciliopathy;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:540	Familial hemophagocytic lymphohistiocytosis	PRF1;STX11;UNC13D;STXBP2	4	Familial Hemophagocytic lymphohistiocytosis (FHL) is a rare primary immunodeficiency characterized by a macrophage activation syndrome (see this term) with an onset usually occurring within a few months or less common several years after birth.	Rare genetic immune disease
Orphanet:568	Microphthalmia, Lenz type	BCOR;NAA10	2	Lenz microphthalmia syndrome is a very rare X-linked inherited form of syndromic microphthalmia (see this term) characterized by unilateral or bilateral microphthalmia (and/or clinical anophthalmia) with or without coloboma in addition to a range of extraocular manifestations such as microcephaly, malformed ears, dental abnormalities (i.e. irregular shape of incisors), skeletal anomalies (duplicated thumbs, syndactyly, clinodactyly, camptodactyly (see these terms)), urogenital anomalies (hypospadias, cryptorchidism, renal dysgenesis, hydroureter) and mild to severe intellectual disability. It is allelic to two disorders: oculofaciocardiodental syndrome and premature aging appearance-developmental delay-cardiac arrhythmia syndrome (see these terms).	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:564	Meckel syndrome	CEP55;TMEM107;RPGRIP1;CEP290;TMEM67;MKS1;RPGRIP1L;CC2D2A;TMEM216;WDPCP;TCTN2;B9D1;B9D2;TMEM231;CSPP1	15	Meckel syndrome (MKS) is a rare, lethal, genetic, multiple congenital anomaly disorder characterized by the triad of brain malformation (mainly occipital encephalocele), large polycystic kidneys, and polydactyly, as well as associated abnormalities that may include cleft lip/palate, cardiac and genital anomalies, central nervous system (CNS) malformations, liver fibrosis, and bone dysplasia.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Ciliopathy;Rare genetic eye disease;Rare genetic bone disease;Rare genetic neurological disorder
Orphanet:289	Ellis Van Creveld syndrome	DYNC2LI1;GLI1;EVC;EVC2	4	Ellis-van Creveld syndrome (EVC) is a skeletal and ectoderlam dysplasia characterized by a tetrad of short stature, postaxial polydactyly, ectodermal dysplasia, and congenital heart defects.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Ciliopathy;Rare genetic cardiac disease;Rare genetic skin disease;Rare genetic bone disease
Orphanet:258	Laminin subunit alpha 2-related congenital muscular dystrophy	LAMA2	1	Congenital muscular dystrophy type 1A (MCD1A) belongs to a group of neuromuscular disorders with onset at birth or infancy characterized by hypotonia, muscle weakness and muscle wasting.	Rare genetic neurological disorder
Orphanet:1646	Partial chromosome Y deletion	USP9Y;DAZ1;DAZ2;DAZ3;DAZ4;DDX3Y;RBMY1A1;TSPY1	8	Male sterility due to chromosome Y deletion is characterized by a severe deficiency of spermatogenesis. Chromosome Y deletions are a frequent genetic cause of male infertility.	Rare chromosomal anomaly;Genetic infertility
Orphanet:169464	Primary CD59 deficiency	CD59	1	Primary CD59 deficiency is a rare, genetic, hematologic and neurologic disease characterized by chronic, Coombs-negative hemolysis associated with early-onset, relapsing, immune-mediated, inflammatory, axonal or demyelinating, sensory-motor, peripheral polyneuropathy and isolated or recurrent cerebrovascular events (in anterior or posterior circulation).	Rare genetic neurological disorder;Rare genetic hematologic disease;Rare genetic immune disease
Orphanet:87	Apert syndrome	FGFR2	1	A frequent form of acrocephalosyndactyly, a group of inherited congenital malformation disorders, characterized by craniosynostosis, midface hypoplasia, and finger and toe anomalies and/or syndactyly.	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic bone disease
Orphanet:169615	Idiopathic central precocious puberty	KISS1R;MKRN3;DLK1	3	NA	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease
Orphanet:97	Familial paroxysmal ataxia	CACNA1A	1	Episodic ataxia type 2 (EA2) is the most frequent form of Hereditary episodic ataxia (EA; see this term) characterized by paroxysmal episodes of ataxia lasting hours, with interictal nystagmus and mildly progressive ataxia.	Rare genetic neurological disorder
Orphanet:169467	Recurrent Neisseria infections due to factor D deficiency	CFD	1	 bacterial infections, resulting from complement factor D deficiency, typically manifesting as recurrent respiratory infections, recurrent meningitis and/or septicemia. Patients typically present fever, purpuric rash, arthralgia, myalgia and undetectable complement factor D plasma concentrations.	Rare genetic immune disease
Orphanet:313	Lamellar ichthyosis	SULT2B1;SDR9C7;ABCA12;ALOX12B;ALOXE3;TGM1;CYP4F22;NIPAL4;LIPN	9	Lamellar ichthyosis (LI) is a keratinization disorder characterized by the presence of large scales all over the body without significant erythroderma.	Rare genetic skin disease;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:169799	Mild hemophilia B	F9	1	Mild hemophilia B is a form of hemophilia B (see this term) characterized by a small deficiency of factor IX leading to abnormal bleeding as a result of minor injuries, or following surgery or tooth extraction.	Rare genetic hematologic disease
Orphanet:169796	Moderately severe hemophilia B	F9	1	Moderately severe hemophilia B is a form of hemophilia B (see this term) characterized by factor IX deficiency leading to abnormal bleeding as a result of minor injuries, or following surgery or tooth extraction.	Rare genetic hematologic disease
Orphanet:169793	Severe hemophilia B	F9	1	Severe hemophilia B is a form of hemophilia B (see this term) characterized by a large deficiency of factor IX leading to frequent spontaneous hemorrhage and abnormal bleeding as a result of minor injuries, or following surgery or tooth extraction.	Rare genetic hematologic disease
Orphanet:171430	Severe congenital nemaline myopathy	ACTA1;NEB;KLHL40;KLHL41;LMOD3	5	Severe congenital nemaline myopathy is a severe form of nemaline myopathy (NM; see this term) characterized by severe hypotonia with little spontaneous movement in neonates.	Rare genetic neurological disorder
Orphanet:171433	Intermediate nemaline myopathy	TPM3;ACTA1;NEB;KLHL41	4	Intermediate nemaline myopathy is a type of nemaline myopathy (NM; see this term) that shows features of typical NM (see this term) in neonates with a more severe progression.	Rare genetic neurological disorder
Orphanet:171436	Typical nemaline myopathy	ACTA1;CFL2;TPM2;NEB;KLHL41;LMOD3	6	Typical nemaline myopathy is a moderate neonatal form of nemaline myopathy (NM; see this term) characterized by facial and skeletal muscle weakness and mild respiratory involvement.	Rare genetic neurological disorder
Orphanet:171439	Childhood-onset nemaline myopathy	TPM2;MYPN;ACTA1;TPM3;NEB;KBTBD13;KLHL41	7	Childhood onset nemaline myopathy, or mild nemaline myopathy is a type of nemaline myopathy (NM; see this terms) characterized by distal muscle weakness, and sometimes slowness of muscle contraction.	Rare genetic neurological disorder
Orphanet:171445	Muscle filaminopathy	FLNC	1	Muscle filaminopathy is a rare myofibrillar myopathy characterized by slowly progressive, proximal skeletal muscle weakness, which is initially more prominent in lower extremities and involves upper extremities with disease progression. Patients present with difficulty climbing stairs, a waddling gait, marked winging of scapula, lower back pain, paresis of limb girdle musculature, hypo-/areflexia and/or mild facial muscle weakness in rare cases. Respiratory muscle weakness is common and cardiac anomalies (conduction blocks, tachycardia, diastolic dysfunction, left ventricular hypertrophy) have been reported in some cases.	Rare genetic neurological disorder
Orphanet:171607	X-linked spastic paraplegia type 34	SPG34	1	X-linked spastic paraplegia type 34 is a pure form of hereditary spastic paraplegia characterized by late childhood- to early adulthood-onset of slowly progressive spastic paraplegia with spastic gait and lower limb hyperreflexia, brisk tendon reflexes and ankle clonus. Lower limb pain and reduced lower limb vibratory sense is also reported in some older adult patients.	Rare genetic neurological disorder
Orphanet:2771	Bruck syndrome	PLOD2;FKBP10	2	Bruck syndrome is characterised by the association of osteogenesis imperfecta and congenital joint contractures.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic odontologic disease
Orphanet:171612	Autosomal dominant spastic paraplegia type 37	SPG37	1	A pure form of hereditary spastic paraplegia characterized by a childhood- to adulthood-onset of slowly progressive spastic gait, extensor plantar responses, brisk tendon reflexes in arms and legs, decreased vibration sense at ankles and urinary dysfunction. Ankle clonus is also reported in some patients.	Rare genetic neurological disorder
Orphanet:1349	Mitochondrial DNA-related cardiomyopathy and hearing loss	MT-TK	1	Maternally inherited cardiomyopathy and hearing loss is a mitochondrial disease described in two unrelated families to date that has a heterogeneous clinical presentation characterized by the association of progressive sensorineural hearing loss with hypertrophic cardiomyopathy and, in the majority of cases, encephalomyopathy symptoms such as ataxia, slurred speech, progressive external opthalmoparesis (PEO), muscle weakness, myalgia, and exercise intolerance.	Rare genetic cardiac disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:171617	Autosomal dominant spastic paraplegia type 38	SPG38	1	A complex hereditary spastic paraplegia characterized by mild to severe lower limbs spasticity, hyperreflexia, extensor plantar responses, pes cavus and significant wasting and weakness of the small hand muscles. Impaired vibration sensation, temporal lobe epilepsy and cognitive dysfunction were also reported.	Rare genetic neurological disorder
Orphanet:171622	Autosomal recessive spastic paraplegia type 32	SPG32	1	Autosomal recessive spastic paraplegia type 32 (SPG32) is a rare, complex type of hereditary spastic paraplegia characterized by a slowly progressive spastic paraplegia (with walking difficulties appearing at onset at 6-7 years of age) associated with mild intellectual disability. Brain imaging reveals thin corpus callosum, cortical and cerebellar atrophy, and pontine dysraphia. The SPG32 phenotype has been mapped to a locus on chromosome 14q12-q21.	Rare genetic neurological disorder
Orphanet:171629	Autosomal recessive spastic paraplegia type 35	FA2H	1	Autosomal recessive spastic paraplegia type 35 is a rare form of hereditary spastic paraplegia characterized by childhood (exceptionally adolescent) onset of a complex phenotype presenting with lower limb (followed by upper limb) spasticity with hyperreflexia and extensor plantar responses, with additional manifestations including progressive dysarthria, dystonia, mild cognitive decline, extrapyramidal features, optic atrophy and seizures. White matter abnormalities and brain iron accumulation have also been observed on brain magnetic resonance imaging.	Rare genetic neurological disorder
Orphanet:861	Treacher-Collins syndrome	TCOF1;POLR1D;POLR1C	3	Treacher-Collins syndrome is a congenital disorder of craniofacial development characterized by bilateral symmetrical oto-mandibular dysplasia without abnormalities of the extremities, and associated with several head and neck defects.	Genetic otorhinolaryngologic disease;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic bone disease
Orphanet:308	Unverricht-Lundborg disease	CSTB;SCARB2;PRICKLE1	3	Unverricht-Lundborg disease (ULD) is a rare progressive myoclonic epilepsy disorder characterized by action- and stimulus-sensitive myoclonus, and tonic-clonic seizures with ataxia, but with only a mild cognitive decline over time.	Rare genetic neurological disorder
Orphanet:199	Cornelia de Lange syndrome	SMC1A;NIPBL;SMC3;HDAC8;RAD21;KMT2A;SETD5	7	).	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic bone disease
Orphanet:930	Idiopathic achalasia	CRLF1;HLA-DQA1;HLA-DQB1;NOS1	4	Idiopathic achalasia (IA) is a primary esophageal motor disorder characterized by loss of esophageal peristalsis and insufficient lower esophageal sphincter (LES) relaxation in response to deglutition.	
Orphanet:171215	Low isolated anorectal malformation	MYH14	1	Low anorectal malformation is a rare, genetic, non-syndromic subtype of anorectal malformation, resulting from a developmental defect during embryogenesis, characterized by a wide spectrum of anorectal anomalies lying below the ischial tuberosity (e.g., anovestibular fistula in female, perineal and anocutaneous fistulas, and anal stenosis). Patients may present with failure to pass meconium, failure to thrive, and chronic constipation.	Rare genetic developmental defect during embryogenesis
Orphanet:1727	22q11.2 microduplication syndrome	TBX1	1	The newly described 22q11.2 microduplication syndrome (dup22q11 syndrome) is the association of a broad clinical spectrum and a duplication of the region that is deleted in patients with DiGeorge or velocardiofacial syndrome (DG/VCFS; see this term), establishing a complementary duplication syndrome.	Rare chromosomal anomaly
Orphanet:169079	Cernunnos-XLF deficiency	NHEJ1	1	Cernunnos-XLF deficiency is a rare form of combined immunodeficiency characterized by microcephaly, growth retardation, and T and B cell lymphopenia.	Inherited cancer-predisposing syndrome;Rare genetic immune disease
Orphanet:169100	Immunodeficiency due to CD25 deficiency	IL2RA	1	Immunodeficiency due to CD25 deficiency is a rare, genetic, primary immunodeficiency due to a defect in adaptive immunity disorder characterized by severe immunodeficiency, presenting with profound susceptibility to viral, fungal and bacterial infections due to impaired CD25-mediated T-regulatory cell function, in association with severe autoimmune disease, such as alopecia universalis, erythrodermia, and autoimmune thyroiditis and enteropathy.	Rare genetic immune disease;Rare genetic gastroenterological disease
Orphanet:169095	Alymphoid cystic thymic dysgenesis	FOXN1	1	A rare, genetic, primary immunodeficiency due to a defect in adaptive immunity characterized by the triad of congenital athymia (resulting in severe T-cell immunodeficiency), congenital alopecia totalis and nail dystrophy. Patients present neonatal or infantile-onset, severe, recurrent, life-threatening infections and low or absent circulating T cells. Additional features reported include erythroderma, lymphoadenopathy, diarrhea and failure to thrive.	Rare genetic immune disease
Orphanet:169082	Combined immunodeficiency due to CD3gamma deficiency	CD3G	1	Combined immunodeficiency due to CD3gamma deficiency is an extremely rare genetic combined primary immunodeficiency characterized by a selective partial lymphopenia (T+/-B+NK+) phenotype and decreased CD3 complex resulting in a variable but usually mild clinical presentation ranging from asymptomatic until adulthood to high susceptibility to infections from early infancy with predominant automimmune manifestations.	Rare genetic immune disease
Orphanet:169085	Susceptibility to respiratory infections associated with CD8alpha chain mutation	CD8A	1	Susceptibility to respiratory infections associated with CD8 alpha chain mutation is a rare primary immunodeficiency due to a defect in adaptive immunity characterized by the absence of CD8+ T cells with normal immunoglobulin and specific antibody titres in blood and susceptibility to recurrent respiratory bacterial and viral infections. Symptom severity range from fatal respiratory insufficiency to mild or asymptomatic phenotypes.	Rare genetic immune disease
Orphanet:168829	Primary peritoneal carcinoma	BRCA1	1	Primary peritoneal carcinoma (PPC) is a rare malignant tumor of the peritoneal cavity of extra-ovarian origin, clinically and histologically similar to advanced-stage serous ovarian carcinoma (see this term).	
Orphanet:753	46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency	SRD5A2	1	46, XY disorder of sex development (DSD; see this term) due to 5-alpha-reductase 2 (SRD5A2) deficiency is a disorder of sex development due to a defect in testosterone (T) metabolism resulting in incomplete intrauterine masculinization. Patients present an ambiguous external genitalia which varies from a female with a blind vaginal pouch to a fully male phenotype with pseudovaginal posterior hypospadias (see this term) or only micropenis.	Genetic infertility;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease;Rare genetic gynecological and obstetrical diseases
Orphanet:868	Triose phosphate-isomerase deficiency	TPI1	1	Triosephosphate isomerase (TPI) deficiency is a severe autosomal recessive inherited multisystem disorder of glycolytic metabolism characterized by hemolytic anemia and neurodegeneration.	Rare inborn errors of metabolism;Rare genetic neurological disorder;Rare genetic hematologic disease
Orphanet:218	Darier disease	ATP2A2	1	Darier disease (DD) is a keratinization disorder characterized by the development of keratotic papules in seborrheic areas and specific nail anomalies.	Rare genetic skin disease
Orphanet:168796	Heart-hand syndrome, Slovenian type	LMNA	1	Heart-hand syndrome of Slovenian type is a rare autosomal dominant form of heart-hand syndrome (see this term), first described in members of a Slovenian family, that is characterized by adult onset, progressive cardiac conduction disease, tachyarrhythmias that can lead to sudden death, dilated cardiomyopathy and brachydactyly, with the hands less severely affected than the feet. Muscle weakness and/or myopathic electromyographic findings have been observed in some cases.	Rare genetic cardiac disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Laminopathy
Orphanet:1465	Coffin-Siris syndrome	ARID2;SMARCB1;SMARCA4;ARID1B;ARID1A;SMARCE1;SOX11;DPF2	8	A rare genetic syndromic intellectual disability characterized by aplasia or hypoplasia of the distal phalanx or nail of the fifth digit, developmental delay, coarse facial features, and other variable clinical manifestations.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:168953	Myeloid/lymphoid neoplasm associated with FGFR1 rearrangement	FGFR1	1	A rare, malignant, neoplastic disease characterized by clonal proliferation of myeloid and/or lymphoid precursors harboring translocations or insertions involving the chromosome band 8p11 and the FGFR1 gene, in the blood, bone marrow and often other tissues as well (spleen, liver, lymph nodes, breast, etc.). It usually presents as myeloproliferative neoplasm with eosinophilia, T lymphoblastic lymphoma with eosinophilia or, less frequently, acute myeloid leukemia. The presenting signs and symptoms include eosinophilia, leukocytosis with leukemoid reaction, monocytosis, fatigue, sweating, weight loss, lymphadenopathy, splenomegaly and/or hepatomegaly. Extranodal involvement may include the tonsils, lungs and breasts.	
Orphanet:168950	Myeloid/lymphoid neoplasm associated with PDGFRB rearrangement	PDGFRB	1	A rare, malignant, neoplastic disease characterized by clonal proliferation of myeloid and/or lymphoid precursors harboring rearrangements in the PDGFRB gene, in the blood, bone marrow and often other tissues as well (spleen, lymph nodes, skin, etc.). It usually presents as chronic myelomonocytic leukemia with eosinophilia, chronic eosinophilic leukemia, atypical chronic myelogenous leukemia, juvenile myelomonocytic leukemia, myelodysplastic syndrome, acute myeloid leukemia or acute lymphoblastic leukemia. Patients usually present with anemia, leukocytosis, monocytosis, eosinophilia and/or splenomegaly, or systemic symptoms, such as fever, sweating and/or weight loss.	
Orphanet:168947	Myeloid/lymphoid neoplasm associated with PDGFRA rearrangement	PDGFRA	1	A rare, malignant, neoplastic disease characterized by clonal proliferation of myeloid and/or lymphoid precursors harboring rearrangements in the PDGFRA gene, in the blood, bone marrow and often other tissues as well (spleen, lymph nodes, skin, etc.). It usually presents as chronic eosinophilic leukemia or, less commonly, as acute myeloid leukemia or T-lymphoblastic leukemia with eosinophilia. Patients usually present with eosinophilia, anemia, thrombocytopenia, neutrophilia, splenomegaly, lymphadenopathy, fever, sweating and/or weight loss. Tissue infiltration by eosinophils can manifest with skin rash, erythema, cough, neurological alterations, gastrointestinal symptoms or, rarely, endomyocardial fibrosis and restrictive cardiomyopathy.	
Orphanet:168940	Chronic eosinophilic leukemia	FIP1L1;PDGFRA	2	NA	
Orphanet:2609	Isolated complex I deficiency	TMEM126B;TIMMDC1;NDUFB11;MT-ND1;MT-ND2;MT-ND3;NDUFAF2;NDUFS1;NDUFS2;NDUFS3;NDUFS4;NDUFS6;NDUFS7;NDUFS8;NDUFV1;NDUFV2;NDUFA1;NDUFAF4;NDUFAF5;NDUFA11;NDUFAF3;NUBPL;FOXRED1;NDUFAF1;NDUFB9;NDUFB3;NDUFB10	27	Isolated complex I deficiency is a rare inborn error of metabolism due to mutations in nuclear or mitochondrial genes encoding subunits or assembly factors of the human mitochondrial complex I (NADH: ubiquinone oxidoreductase) and is characterized by a wide range of manifestations including marked and often fatal lactic acidosis, cardiomyopathy, leukoencephalopathy, pure myopathy and hepatopathy with tubulopathy. Among the numerous clinical phenotypes observed are Leigh syndrome, Leber hereditary optic neuropathy and MELAS syndrome (see these terms).	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:626	Large congenital melanocytic nevus	MC1R;NRAS	2	A large, or giant, congenital melanocytic nevus (LCMN or GCMN) is a pigmented skin lesion of more than 20 cm - or 40 cm- respectively, projected adult diameter, composed of melanocytes, and presenting with an elevated risk of malignant transformation.	Rare genetic tumor
Orphanet:773	Refsum disease	PHYH;PEX7	2	A metabolic disease characterized by anosmia, cataract, early-onset retinitis pigmentosa and possible neurological manifestations, including peripheral neuropathy and cerebellar ataxia. Other features can be deafness, ichthyosis, skeletal abnormalities, and cardiac arrhythmia. It is characterized biochemically by accumulation of phytanic acid in plasma and tissues.	Rare genetic neurological disorder;Rare genetic eye disease;Rare inborn errors of metabolism;Rare genetic skin disease
Orphanet:169154	T-B+ severe combined immunodeficiency due to IL-7Ralpha deficiency	IL7R	1	NA	Rare genetic immune disease
Orphanet:169150	Immunodeficiency due to a late component of complement deficiency	C5;C6;C7;C8A;C8B;C8G;C9	7	Immunodeficiency due to a late component of complement deficiency is a primary immunodeficiency due to an anomaly in either complement components C5, C6, C7, C8 or C9 and is typically characterized by meningitis due to often recurrent meningococcal infections. The prognosis is generally favorable.	Rare genetic immune disease
Orphanet:169160	T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta	CD3D;CD3E;CD247	3	NA	Rare genetic immune disease
Orphanet:169157	T-B+ severe combined immunodeficiency due to CD45 deficiency	PTPRC	1	NA	Rare genetic immune disease
Orphanet:1947	Progressive epilepsy-intellectual disability syndrome, Finnish type	CLN8	1	Progressive epilepsy-intellectual deficit, Finnish type (also known as Northern epilepsy) is a subtype of neuronal ceroid lipofuscinosis (NCL; see this term) characterized by seizures, progressive decline of intellectual capacities and variable loss of vision.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:169147	Immunodeficiency due to a classical component pathway complement deficiency	C2;C4A;C4B;C1QA;C1QB;C1QC;C1S;C1R	8	Immunodeficiency due to a classical component pathway complement deficiency is a primary immunodeficiency due to a deficiency in either complement components C1q, C1r, C1s, C2 or C4 characterized by increased susceptibility to bacterial infections, particularly with encapsulated bacteria, and increased risk for autoimmune disease. Most commonly, these include systemic lupus erythematosus (SLE), SLE-like disease, Henoch-Schonlein purpura, polymyositis and arthralgia. Disease severity is variable and dependent on the complement affected.	Rare genetic immune disease
Orphanet:169142	Recurrent infection due to specific granule deficiency	CEBPE;SMARCD2	2	NA	Rare genetic immune disease
Orphanet:596	X-linked centronuclear myopathy	MTM1	1	X-linked myotubular myopathy (XLMTM) is an inherited neuromuscular disorder defined by numerous centrally placed nuclei on muscle biopsy and clinical features of a congenital myopathy.	Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:610	Bethlem myopathy	COL6A1;COL6A2;COL6A3;COL12A1	4	Bethlem myopathy is a benign autosomal dominant form of slowly progressive muscular dystrophy.	Rare genetic neurological disorder
Orphanet:169186	Autosomal recessive centronuclear myopathy	TTN;SPEG;RYR1;BIN1	4	An inherited neuromuscular disorder defined by numerous centrally placed nuclei on muscle biopsy and clinical features of a congenital myopathy.	Rare genetic neurological disorder
Orphanet:464	Incontinentia pigmenti	IKBKG	1	An X-linked syndromic muti-systemic ectodermal dysplasia presenting neonatally in females with a bullous rash along Blaschko's lines (BL) followed by verrucous plaques and hyperpigmented swirling patterns. It is further characterized by teeth abnormalities, alopecia, nail dystrophy and can affect the retinal and the central nervous system (CNS) microvasculature. It may have other aspects of ectodermal dysplasia such as sweat gland abnormalities. Germline pathogenic variants in males result in embryonic lethality.	Rare genetic neurological disorder;Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:169189	Autosomal dominant centronuclear myopathy	RYR1;DNM2;MYF6;BIN1;MTMR14	5	A rare, inherited neuromuscular disorder defined by numerous centrally placed nuclei on muscle biopsy and clinical features of a congenital myopathy.	Rare genetic neurological disorder
Orphanet:44	Neonatal adrenoleukodystrophy	PEX2;PEX1;PEX10;PEX12;PEX13;PEX14;PEX16;PEX19;PEX26;PEX3;PEX5;PEX6;PEX11B	13	A variant of intermediate severity of the PBD-Zellweger syndrome spectrum (PBD-ZSS) charcterized by hypotonia, leukodystrophy, and vision and sensorineural hearing deficiencies. Phenotypic overlap is seen between NALD and infantile Refsum disease (IRD).	Rare genetic eye disease;Rare genetic neurological disorder;Rare genetic hepatic disease;Rare inborn errors of metabolism;Rare genetic endocrine disease
Orphanet:56	Alkaptonuria	HGD	1	A rare disorder of phenylalanine and tyrosine metabolism characterized by the accumulation of homogentisic acid (HGA) and its oxidized product, benzoquinone acetic acid (BQA), in various tissues (e.g. cartilage, connective tissue) and body fluids (urine, sweat), causing urine to darken when exposed to air as well as grey-blue coloration of the sclera and ear helix (ochronosis), and a disabling joint disease involving both the axial and peripheral joints (ochronotic arthropathy).	Rare inborn errors of metabolism;Rare genetic skin disease;Rare genetic eye disease
Orphanet:963	Acromegaly	AIP;GPR101	2	An acquired disorder related to excessive production of growth hormone (GH) and characterized by progressive somatic disfigurement (mainly involving the face and extremities) and systemic manifestations.	Rare genetic endocrine disease
Orphanet:1059	Blue rubber bleb nevus	TEK	1	A rare vascular malformation disorder with cutaneous and visceral lesions frequently associated with serious, potentially fatal bleeding and anemia.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:22	Succinic semialdehyde dehydrogenase deficiency	ALDH5A1	1	A rare neurometabolic disorder of gamma-aminobutyric acid (GABA) metabolism with a nonspecific clinical presentation (ranging from mild to severe) with the most frequent symptoms being cognitive impairment with prominent deficit in expressive language, hypotonia, ataxia, epilepsy, and behavioral dysregulation.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:29	Mevalonic aciduria	MVK	1	A rare, very severe form of mevalonate kinase deficiency (MKD) characterized by dysmorphic features, failure to thrive, psychomotor delay, ocular involvement, hypotonia, progressive ataxia, myopathy, and recurrent inflammatory episodes.	Rare genetic eye disease;Rare genetic systemic or rheumatologic disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:245	Nager syndrome	SF3B4	1	A congenital malformation syndrome characterized by mandibulofacial dystosis (malar hypoplasia, micrognathia, external ear malformations) and variable preaxial limb defects.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease
Orphanet:30	Hereditary orotic aciduria	UMPS	1	) localized to chromosome 3q13.	Rare inborn errors of metabolism;Rare genetic hematologic disease
Orphanet:36	Acrocallosal syndrome	SUFU;GLI3;KIF7	3	A polymalformative syndrome characterized by agenesis of corpus callosum (CC), distal anomalies of limbs, minor craniofacial anomalies and intellectual deficit.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:915	Aarskog-Scott syndrome	FGD1	1	A rare developmental disorder characterized by facial, limbs and genital features, and a disproportionate acromelic short stature.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare genetic urogenital disease;Rare genetic skin disease
Orphanet:2614	Nail-patella syndrome	LMX1B	1	Nail-patella syndrome (NPS) is a rare hereditary patellar dysostosis characterized by nail hypoplasia or aplasia, aplastic or hypoplastic patellae, elbow dysplasia, and the presence of iliac horns as well as renal and ocular anomalies.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic skin disease;Rare genetic eye disease
Orphanet:33	Isovaleric acidemia	IVD	1	An autosomal recessively inherited organic aciduria characterized by a deficiency in isovaleryl-CoA dehydrogenase, that has wide clinical variability and that can present in infancy with acute manifestations of vomiting, failure to thrive, seizures, lethargy, a characteristic ''sweaty feet'' odor, acute pancreatitis and mild to severe developmental delay or in childhood with metabolic acidosis (brought on by prolonged fasting, an increased intake of protein-rich food or infections) and that can be fatal if not treated immediately. Chronic intermittent presentations and asymptomatic patients have also been reported.	Rare inborn errors of metabolism
Orphanet:819	Smith-Magenis syndrome	DEAF1;RAI1;RAI1;FLII;IQSEC2	5	Smith-Magenis syndrome (SMS) is a complex genetic disorder characterized by variable intellectual deficit, sleep disturbance, craniofacial and skeletal anomalies, psychiatric disorders, and speech and motor delay.	Rare genetic neurological disorder;Rare chromosomal anomaly;Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease
Orphanet:168615	Hereditary persistence of alpha-fetoprotein	AFP	1	Hereditary persistence of alpha-fetoprotein is a benign genetic condition characterized by persistence of high alpha-fetoprotein (AFP) levels throughout life, with no associated clinical disability and thus no need for specific therapy	
Orphanet:168612	Congenital deficiency in alpha-fetoprotein	AFP	1	Congenital deficiency in alpha-fetoprotein is a benign genetic condition characterized by a dramatically decreased level of alpha-fetoprotein in fetus or neonate.	
Orphanet:1452	Cleidocranial dysplasia	RUNX2	1	Cleidocranial dysplasia (CCD) is a rare genetic developmental abnormality of bone characterized by hypoplastic or aplastic clavicles, persistence of wide-open fontanels and sutures and multiple dental abnormalities.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:168629	Autosomal thrombocytopenia with normal platelets	MASTL;CYCS	2	NA	Rare genetic hematologic disease
Orphanet:168624	Familial scaphocephaly syndrome, McGillivray type	FGFR2	1	Familial scaphocephaly syndrome, McGillivray type is a rare newly described craniosynostosis (see this term) syndrome characterized by scaphocephaly, macrocephaly, severe maxillary retrusion, and mild intellectual disability.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:193	Cohen syndrome	VPS13B	1	Cohen syndrome (CS) is a rare genetic developmental disorder characterized by microcephaly, characteristic facial features, hypotonia, non-progressive intellectual deficit, myopia and retinal dystrophy, neutropenia and truncal obesity.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic immune disease;Rare genetic eye disease;Rare genetic endocrine disease
Orphanet:168583	Hereditary North American Indian childhood cirrhosis	UTP4	1	Hereditary North American Indian childhood cirrhosis is a severe autosomal recessive intrahepatic cholestasis that has only been described in aboriginal children from northwestern Quebec. Manifesting first as transient neonatal jaundice, the disease evolves into periportal fibrosis and cirrhosis during a period ranging from childhood to adolescence.	Rare inborn errors of metabolism;Rare genetic hepatic disease
Orphanet:1334	Chronic mucocutaneous candidiasis	CLEC7A;IL17RA;IL17F;TRAF3IP2;IL17RC	5	.	Rare genetic skin disease;Rare genetic immune disease
Orphanet:168577	Hereditary cryohydrocytosis with reduced stomatin	SLC2A1	1	Hereditary cryohydrocytosis with reduced stomatin is a rare hemolytic anemia characterized by combination of neurologic features, such as psychomotor delay, seizures, variable movement disorders, and hemolytic anemia with stomatocytosis, resulting in cation-leaky erythrocytes, pseudohyperkalemia, hemolytic crises and hepatosplenomegaly. Cataracts are also a presenting feature.	Rare genetic neurological disorder;Rare genetic hematologic disease
Orphanet:1369	Congenital cataract-hypertrophic cardiomyopathy-mitochondrial myopathy syndrome	SLC25A4;AGK	2	Congenital cataract - hypertrophic cardiomyopathy - mitochrondrial myopathy (CCM) is a mitochondrial disease (see this term) characterized by cataracts, hypertrophic cardiomyopathy, muscle weakness and lactic acidosis after exercise.	Rare genetic cardiac disease;Rare genetic eye disease;Rare inborn errors of metabolism;Rare genetic developmental defect during embryogenesis
Orphanet:168593	Sudden infant death-dysgenesis of the testes syndrome	TSPYL1	1	Sudden infant death with dysgenesis of the testes (SIDDT) syndrome is a lethal condition in infants with dysgenesis of testes.	Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease
Orphanet:168588	Hyperandrogenism due to cortisone reductase deficiency	H6PD;HSD11B1	2	A rare, genetic, endocrine disease characterized by defect in conversion of cortisone to active cortisol, resulting in ACTH-mediated excessive androgen release from adrenal glands. Premature adrenarche is typical with precocious pseudopuberty, proportionate tall stature and accelerated bone maturation in males, and hirsutism, oligoamenorrhea, central obesity and infertility in females. Imaging studies may indicate adrenal hyperplasia.	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease
Orphanet:168601	Congenital enteropathy due to enteropeptidase deficiency	TMPRSS15	1	Congenital enteropathy due to enteropeptidase deficiency is a rare, genetic, gastroenterological disease characterized by early-onset failure to thrive, edema, hypoproteinemia, diarrhea and fat malabsorption (or steatorrhea) in the presence of very low or absent trypsin activity in duodenal fluid. Celiac disease, or other pancreatic or mucosal disorders, may be associated.	Rare genetic gastroenterological disease
Orphanet:168598	Brain demyelination due to methionine adenosyltransferase deficiency	MAT1A	1	Hypermethioninemia due to methionine adenosyltransferase deficiency is a very rare metabolic disorder resulting in isolated hepatic hypermethioninemia that is usually benign due to partial inactivation of enzyme activity. Rarely patients have been found to have an odd odor or neurological disorders such as brain demyelination.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:168609	Mitochondrial non-syndromic sensorineural deafness with susceptibility to aminoglycoside exposure	TRMU;MT-CO1;MT-ND4;MT-RNR1;MT-TS1	5	NA	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:168606	Seborrhea-like dermatitis with psoriasiform elements	ZNF750	1	Seborrhea-like dermatitis with psoriasiform elements is a rare, genetic, epidermal disorder characterized by a chronic, diffuse, fine, scaly erythematous rash on the face (predominantly the chin, nasolabial folds, eyebrows), around the earlobes and over the scalp, associated with hyperkeratosis over elbows, knees, palms, soles and metacarpophalangeal joints, in the absence of associated rheumatological or neurological disorders. Cold weather, emotional stress and strenuous physical activity may exacerbate symptoms.	Rare genetic skin disease
Orphanet:1154	Arthrogryposis-oculomotor limitation-electroretinal anomalies syndrome	PIEZO2	1	Distal arthrogryposis type 5 is an inherited developmental defect syndrome characterized by multiple congenital contractures of limbs, without primary neurologic and/or muscle disease that affects limb function, and ocular anomalies (ptosis, external ophtalmoplegia and/or strabismus). Intelligence is normal.	Rare genetic developmental defect during embryogenesis
Orphanet:168558	46,XY disorder of sex development-adrenal insufficiency due to CYP11A1 deficiency	CYP11A1	1	 gene. Milder cases may present delayed onset of adrenal gland dysfunction and genitalia phenotype may range from normal male to female in individuals with 46,XY karyotype. Imaging studies reveal hypoplastic/absent adrenal glands and biochemical findings include low serum cortisol, mineralocorticoids, androgens, and sodium, with elevated potassium levels.	Rare genetic endocrine disease;Rare genetic gynecological and obstetrical diseases;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease
Orphanet:124	Blackfan-Diamond anemia	RPL18;RPS27;RPL27;TSR2;RPL35;RPS19;RPS24;GATA1;RPS17;RPS7;RPL5;RPL11;RPL35A;RPS10;RPS26;RPL26;RPL15;RPS29;RPS28	19	Blackfan-Diamond anemia (DBA) is a congenital aregenerative and often macrocytic anemia with erythroblastopenia.	Inherited cancer-predisposing syndrome;Rare inborn errors of metabolism;Rare genetic developmental defect during embryogenesis;Rare genetic hematologic disease
Orphanet:168563	46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome	DHH	1	46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome is a rare, genetic, developmental defect during embryogenesis disorder characterized by partial (unilateral testis, persistence of Müllerian duct structures) or complete (streak gonads only) gonadal dysgenesis, usually manifesting with primary amenorrhea in individuals with female phenotype but 46,XY karyotype, and sensorimotor dysmyelinating minifascicular polyneuropathy, which presents with numbness, weakness, exercise-induced muscle cramps, sensory disturbances and reduced/absent deep tendon reflexes. Germ cell tumors (seminoma, dysgerminoma, gonadoblastoma) may develop from the gonadal tissue.	Rare genetic gynecological and obstetrical diseases;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease
Orphanet:168566	Fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3	TSFM	1	Combined oxidative phosphorylation deficiency type 3 is an extremely rare clinically heterogenous disorder described in about 5 patients to date. Clinical signs included hypotonia, lactic acidosis, and hepatic insufficiency, with progressive encephalomyopathy or hypertrophic cardiomyopathy.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:168569	H syndrome	SLC29A3	1	A rare cutaneous disease and a systemic inherited histiocytosis mainly characterized by hyperpigmentation, hypertrichosis, hepatosplenomegaly, heart anomalies, hearing loss, hypogonadism, low height, and occasionally, hyperglycemia/diabetes mellitus. Due to overlapping clinical features, it is now considered to include pigmented hypertrichosis with insulin dependent diabetes mellitus syndrome (PHID), Faisalabad histiocytosis (FHC) and familial sinus histiocytosis with massive lymphadenopathy (FSHML). Some cases of dysosteosclerosis may also represent the syndrome.	Genetic otorhinolaryngologic disease;Rare genetic skin disease;Rare genetic endocrine disease
Orphanet:1310	Caffey disease	COL1A1	1	Caffey disease is an osteosclerotic dysplasia characterized by acute inflammation with massive subperiosteal new bone formation usually involving the diaphyses of the long bones, as well as the ribs, mandible, scapulae, and clavicles. The disease is associated with fever, irritability pain and soft tissue swelling, with onset around the age of 2 months and resolving spontaneously by the age of 2 years. However, prenatal disease onset has also been described.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:168572	Native American myopathy	STAC3	1	Native American myopathy (NAM) is a neuromuscular disorder characterized by weakness, arthrogryposis, kyphoscoliosis, short stature, cleft palate, ptosis and susceptibility to malignant hyperthermia during anesthesia.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:125	Bloom syndrome	BLM	1	Bloom syndrome is a rare disorder associated with pre- and postnatal growth deficiency, a telangiectatic erythematous rash of the face and other sun-exposed areas, insulin resistance and predisposition to early onset and recurrent cancer of multiple organ systems.	Inherited cancer-predisposing syndrome;Rare genetic immune disease;Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:90	Argininemia	ARG1	1	A rare autosomal recessive amino acid metabolism disorder characterized clinically by variable degrees of hyperammonemia, developing from about 3 years of age, and leading to progressive loss of developmental milestones and spasticity in the absence of treatment.	Rare inborn errors of metabolism
Orphanet:1065	Aniridia-cerebellar ataxia-intellectual disability syndrome	ITPR1;PAX6	2	A rare, congenital, neurological disorder characterized by the association of partial bilateral aniridia with non-progressive cerebellar ataxia, and intellectual disability.	Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:168448	Spondyloepimetaphyseal dysplasia, Bieganski type	AIFM1	1	NA	NA
Orphanet:168454	Spondyloepimetaphyseal dysplasia, Geneviève type	NANS	1	Spondyloepimetaphyseal dysplasia, Geneviève type is a rare primary bone dysplasia characterized by severe developmental delay and skeletal dysplasia (including short stature, premature carpal ossification, platyspondyly, longitudinal metaphyseal striations, and small epiphyses), as well as moderate to severe intellectual disability and facial dysmorphism, including prominent forehead, mild synophrys, depressed nasal bridge, prominent bulbous nasal tip and full lips.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:1146	Digitotalar dysmorphism	NALCN;TNNI2;TNNT3;TPM2;MYH3;MYBPC1	6	Digitotalar dysmorphism, also known as distal arthrogryposis type 1 (DA1), is an autosomal dominant congenital anomaly characterized by contractures of the distal regions of the hands and feet with no facial involvement or any additional anomalies. It is the most common type of distal arthrogryposis (see this term).	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:1143	Neurogenic arthrogryposis multiplex congenita	ERGIC1	1	Neurogenic arthrogryposis multiplex congenita is a form of arthrogryposis multiplex congenita characterized by congenital immobility of the limbs with fixation of multiple joints and muscle wasting. This condition is secondary to neurogenic muscular atrophy.	Rare genetic developmental defect during embryogenesis
Orphanet:1147	Sheldon-Hall syndrome	NALCN;TNNI2;TNNT3;TPM2;MYH3	5	Sheldon-Hall syndrome (SHS) is a rare multiple congenital contracture syndrome characterized by contractures of the distal joints of the limbs, triangular face, downslanting palpebral fissures, small mouth, and high arched palate.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:246	Postaxial acrofacial dysostosis	DHODH	1	Postaxial acrofacial dysostosis (POADS) is a type of acrofacial dysostosis (see this term) characterised by mandibular and malar hypoplasia, small and cup-shaped ears, lower lid ectropion, and symmetrical postaxial limb deficiencies with absence of the fifth digital ray and ulnar hypoplasia.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease
Orphanet:1775	Dyskeratosis congenita	DKC1;TERT;TERC;TINF2;NOP10;NHP2;USB1;WRAP53;CTC1;RTEL1;PARN	11	A rare ectodermal dysplasia syndrome that often presents with the classic triad of nail dysplasia, skin pigmentary changes, and oral leukoplakia associated with a high risk of bone marrow failure (BMF) and cancer.	Rare genetic neurological disorder;Rare genetic hematologic disease;Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic immune disease;Rare genetic eye disease
Orphanet:1764	Familial dysautonomia	ELP1	1	A rare hereditary sensory and autonomic neuropathy characterized by decreased pain and temperature perception, absent deep tendon reflexes, proprioceptive ataxia, afferent baroreflex failure and progressive optic neuropathy.	Rare genetic skin disease;Rare genetic eye disease;Rare genetic neurological disorder
Orphanet:235	Dubowitz syndrome	LIG4;NSUN2	2	Dubowitz syndrome (DS) is a rare multiple congenital syndrome characterized primarly by growth retardation, microcephaly, distinctive facial dysmorphism, cutaneous eczema, a mild to severe intellectual deficit and genital abnormalities.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic skin disease
Orphanet:239	Dyggve-Melchior-Clausen disease	DYM	1	Dyggve-Melchior-Clausen disease (DMC) is a rare skeletal disorder belonging to the group of spondyloepimetaphyseal dysplasias (see this term).	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:395	Homocystinuria due to methylene tetrahydrofolate reductase deficiency	MTHFR	1	Homocystinuria due to methylene tetrahydrofolate reductase (MTHFR) deficiency is a metabolic disorder characterised by neurological manifestations.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:147	Carbamoyl-phosphate synthetase 1 deficiency	CPS1	1	A rare, severe disorder of urea cycle metabolism typically characterized by either a neonatal-onset of severe hyperammonemia that occurs few days after birth and manifests with lethargy, vomiting, hypothermia, seizures, coma and death or a presentation outside the newborn period at any age with (sometimes) milder symptoms of hyperammonemia.	Rare inborn errors of metabolism
Orphanet:23	Argininosuccinic aciduria	ASL	1	A rare, genetic disorder of urea cycle metabolism typically characterized by either a severe, neonatal-onset form that manifests with hyperammonemia accompanied with vomiting, hypothermia, lethargy and poor feeding in the first few days of life, or late-onset forms that manifest with stress- or infection-induced episodic hyperammonemia or, in some, behavioral abnormalities and/or learning disabilities, or chronic liver disease. Patients often manifest liver dysfunction.	Rare inborn errors of metabolism
Orphanet:45	Adenosine monophosphate deaminase deficiency	AMPD1;AMPD3	2	A rare metabolic disorder for which two forms have been described. Lack of activity of the erythrocyte isoform of adenosine monophosphate (AMP) deaminase has been described in subjects with low plasma uric acid levels without obvious clinical relevance and will not be described further. Myoadenylate deaminase deficiency is an inherited disorder of muscular energy metabolism with a lack of AMP deaminase activity in skeletal muscle. It is characterised by exercise-induced muscle pain, cramps and/or early fatigue.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:226	Dihydropteridine reductase deficiency	QDPR	1	Dihydropteridine reductase (DHPR) deficiency is a severe form of hyperphenylalaninemia (HPA) due to impaired regeneration of tetrahydrobiopterin (BH4) (see this term), leading to decreased levels of neurotransmitters (dopamine, serotonin) and folate in cerebrospinal fluid, and causing neurological symptoms such as psychomotor delay, hypotonia, seizures, abnormal movements, hypersalivation, and swallowing difficulties.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:1556	Cutis marmorata telangiectatica congenita	ARL6IP6	1	Cutis marmorata telangiectatica congenita (CMTC) is a congenital localized or generalized vascular anomaly characterized by a persistent cutis marmorata pattern with a marbled bluish to deep purple appearance, spider nevus-like telangiectasia, phlebectasia and, occasionally, ulceration and atrophy of the affected skin.	
Orphanet:1496	Corpus callosum agenesis-neuronopathy syndrome	SLC12A6	1	"Corpus callosum agenesis-neuronopathy syndrome is a neurodegenerative disorder characterized by severe progressive sensorimotor neuropathy beginning in infancy with resulting hypotonia, areflexia, amyotrophy and variable degrees of dysgenesis of the corpus callosum. Additional features include mild-to-severe intellectual and developmental delays, and psychiatric manifestations that include paranoid delusions, depression, hallucinations, and ""autistic-like"" features. Affected individuals are usually wheelchair restricted in the second decade of life and die in the third decade of life. The disease is inherited as an autosomal recessive trait."	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:417	Neonatal severe primary hyperparathyroidism	CASR	1	 3.5 mM) from birth and associated with major hyperparathyroidism.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic endocrine disease
Orphanet:2248	Hypoplastic left heart syndrome	GJA1;NKX2-5	2	A rare, congenital, non-syndromic, heart malformation characterized by under development of the left-sided cardiac structures (including left ventricle, ascending aorta, aortic arch, and mitral and/or aortic valve) such that the left heart is unable to provide adequate systemic cardiac output.	
Orphanet:2140	Congenital diaphragmatic hernia	ZFPM2;GATA6	2	Congenital diaphragmatic hernia (CDH) is a posterolateral defect of the diaphragm that allows passage of abdominal viscera into the thorax, leading to respiratory insufficiency and persistent pulmonary hypertension with high mortality.	
Orphanet:2116	Hartnup disease	SLC6A19	1	A rare metabolic disorder belonging to the neutral aminoacidurias, mainly characterized by skin photosensitivity, ocular and neuropsychiatric features, due to abnormal renal and gastrointestinal transport of neutral amino acids (tryptophan, alanine, asparagine, glutamine, histidine, isoleucine, leucine, phenylalanine, serine, threonine, tyrosine and valine).	Rare inborn errors of metabolism;Rare genetic skin disease;Rare genetic neurological disorder;Rare genetic renal disease
Orphanet:2118	Hawkinsinuria	HPD	1	Hawkinsinuria is an inborn error of tyrosine metabolism characterized by failure to thrive, persistent metabolic acidosis, fine and sparse hair, and excretion of the unusual cyclic amino acid metabolite, hawkinsin ((2-l-cystein-S-yl, 4-dihydroxycyclohex-5-en-1-yl)acetic acid), in the urine.	Rare inborn errors of metabolism
Orphanet:351	Galactosialidosis	CTSA	1	Galactosialidosis is a lysosomal storage disease characterized by coarse facial features, macular ''cherry red spot'', and dysostosis multiplex. Clinical presentation can be heterogenous ranging from a severe, early-onset, rapidly progressive infantile form to late onset, slowly progressive juvenile/adult form.	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:2020	Congenital fiber-type disproportion myopathy	MAP3K20;ACTA1;SELENON;TPM2;TPM3;MYL2;ITGA7;HACD1	8	A rare genetic, congenital, non-dystrophic myopathy characterized by neonatal or infantile-onset hypotonia and mild to severe generalized muscle weakness.	Rare genetic neurological disorder
Orphanet:2053	Freeman-Sheldon syndrome	NALCN;MYH3	2	Freeman-Sheldon syndrome (FSS) is a very rare, multiple congenital contractures syndrome characterized by a microstomia with a whistling appearance of the mouth, distinctive facies, club foot and joint contractures. FSS is the most severe form of distal arthrogryposis.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:1933	Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria	SUCLA2	1	Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria is characterised by the association of a mitochondrial encephalomyopathy and an aminoacidopathy. It has been described in two brothers presenting with developmental delay, neurological signs, deafness, exercise intolerance, lactic acidosis and elevation of several plasmatic amino acids. Mitochondria morphology was found to be abnormal on muscle biopsy. Transmission is likely to be linked to maternal mitochondrial DNA.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic gastroenterological disease;Rare genetic neurological disorder
Orphanet:1880	Ebstein malformation	MYH7	1	Ebstein's malformation is a rare congenital cardiac anomaly characterized by rotational displacement of the septal and inferior leaflets of the tricuspid valve such that they are hinged within the right ventricle, rather than as expected at the atrioventricular junction.	Rare genetic cardiac disease
Orphanet:1885	Isolated ectopia lentis	FBN1;ADAMTSL4	2	Isolated ectopia lentis (IEL) is a rare, clinically variable, eye disorder characterized by dislocation of the lens, often causing significant reduction in visual acuity.	Rare genetic systemic or rheumatologic disease;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:635	Neuroblastoma	MYCN;LMO1;PHOX2B;TOP2A;ALK;ALK;HACE1;LIN28B	8	Neuroblastoma is a malignant tumor of neural crest cells, the cells that give rise to the sympathetic nervous system, which is observed in children.	
Orphanet:2612	Linear nevus sebaceus syndrome	HRAS;KRAS;NRAS	3	Linear nevus sebaceous syndrome (LNSS) is characterized by the association of a large sebaceous nevus, usually appearing on the face or on the scalp, with a broad spectrum of abnormalities that may affect every organ system, including the central nervous system (brain neoplasms, hemimegalencephaly and lateral ventricle enlargement).	Rare genetic tumor;Rare genetic developmental defect during embryogenesis
Orphanet:2635	Metatropic dysplasia	TRPV4	1	Metatropic dysplasia (MTD) is a rare spondyloepimetaphyseal dysplasia characterized by a long trunk and short limbs in infancy followed by severe and progressive kyphoscoliosis causing a reversal in proportions during childhood (short trunk and long limbs) and a final short stature in adulthood.	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:606	Proximal myotonic myopathy	CNBP	1	Myotonic dystrophy type 2 (MD2), also known as proximal myotonic myopathy, is a very rare genetic multi-system disorder of late childhood or adult-onset characterized by mild myotonia, muscle weakness, and rarely cardiac conduction disorders.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease;Genetic infertility;Rare genetic neurological disorder
Orphanet:705	Pendred syndrome	SLC26A4;KCNJ10;FOXI1	3	A syndromic genetic deafness clinically variable characterized by bilateral sensorineural hearing loss and euthyroid goiter.	Genetic otorhinolaryngologic disease;Rare genetic endocrine disease
Orphanet:2801	Juvenile Paget disease	TNFRSF11B;TNFRSF11A	2	Juvenile Paget disease is a very rare form of Paget disease of the bone characterized by a general increase in bone turnover with increased bone resorption and deposition, resulting in cortical and trabecular thickening, and clinically presenting as progressive skeletal deformities, growth impairment, fractures, vertebral collapse, skull enlargement and sensorineural hearing loss.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2785	Osteopetrosis with renal tubular acidosis	CA2	1	Osteopetrosis with renal tubular acidosis is a rare disorder characterized by osteopetrosis (see this term), renal tubular acidosis (RTA), and neurological disorders related to cerebral calcifications.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic renal disease
Orphanet:2744	Horizontal gaze palsy with progressive scoliosis	ROBO3	1	Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare congenital autosomal recessive disease, presenting in children and adolescents, and characterized by progressive scoliosis along with the absence of conjugate horizontal eye movements and associated with failure of the somatosensory and corticospinal neuronal tracts to decussate in the medulla.	Rare genetic eye disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:2746	Opsismodysplasia	INPPL1	1	Opsismodysplasia is a skeletal dysplasia characterized by congenital dwarfism and facial dysmorphism.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2971	Peroxisomal acyl-CoA oxidase deficiency	ACOX1	1	Peroxisomal acyl-CoA oxidase deficiency is a rare neurodegenerative disorder that belongs to the group of inherited peroxisomal disorders and is characterized by hypotonia and seizures in the neonatal period and neurological regression in early infancy.	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:2970	Prune belly syndrome	CHRM3	1	Prune belly syndrome is a rare congenital disorder, belonging to the group of fetal lower urinary tract obstructions (LUTO), involving variable dilation of the lower urinary tract in association with partial or complete absence of the lateral and inferior abdominal wall musculature and in males bilateral non-palpable undescended testes.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis
Orphanet:744	Proteus syndrome	PTEN;AKT1	2	Proteus syndrome (PS) is a very rare and complex hamartomatous overgrowth disorder characterized by progressive overgrowth of the skeleton, skin, adipose, and central nervous systems.	Rare genetic developmental defect during embryogenesis;Inherited cancer-predisposing syndrome;Rare genetic bone disease;Rare genetic neurological disorder
Orphanet:2903	Familial spontaneous pneumothorax	FLCN	1	Familial spontaneous pneumothorax is a rare, genetic pulmonary disease characterized by the uni- or bilateral accumulation of air in the pleural cavity in persons with a positive family history and no underlying lung disease or previous chest trauma. Patients typically present dyspnea associated with acute onset of sharp and steady pleutiric chest pain of variable severity (which resolves within 24h even though pneumothorax is still present). Reflex tachycardia and/or respiratory or circulatory compromise may be observed. Other syndromes (e.g. Birt-Hogg-Dube, Marfan or Ehlers-Danlos syndromes) may be associated.	
Orphanet:2901	Neuralgic amyotrophy	SEPT9	1	Neuralgic amyotrophy (NA) is an uncommon disorder of the peripheral nervous system characterized by the sudden onset of extreme pain in the upper extremity followed by rapid multifocal motor weakness and atrophy and a slow recovery in months to years. NA includes both an idiopathic (INA, also known as Parsonage-Turner syndrome) and hereditary (HNA) form.	
Orphanet:718	Isolated Pierre Robin syndrome	SOX9	1	Pierre-Robin syndrome (or Pierre-Robin sequence) is characterised by triad of orofacial morphological anomalies consisting of retrognathism, glossoptosis and a posterior median velopalatal cleft.	Rare genetic developmental defect during embryogenesis
Orphanet:3071	Costello syndrome	HRAS	1	A rare syndrome with intellectual disability, characterized by failure to thrive, short stature, joint laxity, soft skin, and distinctive facial features. Cardiac and neurological involvement is common and there is an increased lifetime risk of certain tumors. Costello syndrome belongs to the RASopathies, a group of conditions resulting from germline derived point mutations affecting the RAS-mitogen activated protein kinase pathway.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Inherited cancer-predisposing syndrome;Rare genetic cardiac disease;Rare genetic skin disease;RASopathy
Orphanet:763	Pycnodysostosis	CTSK	1	Pycnodysostosis is a genetic lysosomal disease characterized by osteosclerosis of the skeleton, short stature and brittle bones.	Rare inborn errors of metabolism;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2301	Congenital short bowel syndrome	FLNA;CLMP	2	Congenital short bowel syndrome is a rare intestinal disorder of neonates of unknown etiology. Patients are born with a short small bowel (less than 75 cm in length) that compromises proper intestinal absorption and leads chronic diarrhea, vomiting and failure to thrive.	Rare genetic developmental defect during embryogenesis;Rare genetic gastroenterological disease
Orphanet:469	Hereditary fructose intolerance	ALDOB	1	Hereditary fructose intolerance (HFI) is an autosomal recessive disorder of fructose metabolism (see this term), resulting from a deficiency of hepatic fructose-1-phosphate aldolase activity and leading to gastrointestinal disorders and postprandial hypoglycemia following fructose ingestion. HFI is a benign condition when treated, but it is life-threatening and potentially fatal if left untreated.	Rare inborn errors of metabolism;Rare genetic hepatic disease;Rare genetic gastroenterological disease;Rare genetic renal disease
Orphanet:2308	Jacobsen syndrome	FLI1	1	A multiple congenital anomaly/mental retardation (MCA/MR) contiguous gene syndrome caused by partial deletion of the long arm of chromosome 11.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic hematologic disease;Rare chromosomal anomaly
Orphanet:2318	Joubert syndrome with oculorenal defect	CEP290;CC2D2A;TMEM216;TMEM237;TMEM138;ZNF423;TMEM231	7	A rare subtype of Joubert syndrome (JS) and related disorders (JSRD) characterized by the neurological features of JS associated with both renal and ocular disease.	Rare genetic renal disease;Ciliopathy;Rare genetic eye disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:180188	Isolated congenital breast hypoplasia/aplasia	PTPRF	1	A rare breast malformation characterized by congenital absence of breast and nipple (amastia), or nipple or mammary gland (athelia or amazia, respectively). It can be unilateral or bilateral and may occur as an isolated malformation or be associated with a syndrome or cluster of other anomalies.	
Orphanet:2253	Foveal hypoplasia-presenile cataract syndrome	PAX6	1	Foveal hypoplasia-presenile cataract syndrome is a rare, genetic ocular disease characterized by congenital nystagmus (horizontal, vertical and/or torsional), foveal hypoplasia, presenile cataracts (with typical onset in the second to third decade of life), and normal irides. Corneal pannus and/or optic nerve hypoplasia may also be present.	Rare genetic eye disease
Orphanet:2300	Multiple intestinal atresia	TTC7A	1	Multiple intestinal atresia is a rare form of intestinal atresia characterized by the presence of numerous atresic segments in the small bowel (duodenum) or large bowel and leading to symptoms of intestinal obstruction: vomiting, abdominal bloating and inability to pass meconium in newborns.	Rare genetic immune disease;Rare genetic developmental defect during embryogenesis
Orphanet:502	Trichorhinophalangeal syndrome type 2	TRPS1;EXT1	2	A very rare, genetic, multiple congenital anomaly disorder characterized by bone abnormalities, distinctive facial features, multiple exostoses, and intellectual disability.	Rare genetic developmental defect during embryogenesis;Rare chromosomal anomaly;Rare genetic bone disease;Rare genetic skin disease
Orphanet:477	KID syndrome	GJB2;GJB6	2	A rare congenital ectodermal disorder characterized by vascularizing keratitis, hyperkeratotic skin lesions and hearing loss.	Genetic otorhinolaryngologic disease;Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:2343	Isolated cloverleaf skull syndrome	ERF	1	A form of craniosynostosis involving multiple sutures (coronal, lambdoidal, sagittal and metopic) characterized by a trilobular skull of varying severity (frontal towering and bossing, temporal bulging and a flat posterior skull), dysmorphic features (downslanting palpebral fissures, midface hypoplasia, and extreme proptosis) and that is complicated by hydrocephalus, cerebral venous hypertension, developmental delay/intellectual disability and hind brain herniation.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2377	Laurence-Moon syndrome	PNPLA6	1	A very rare genetic multisystemic disorder characterized by pituitary dysfunction, ataxia, peripheral neuropathy, spastic paraplegia, and chorioretinal dystrophy.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility;Rare genetic eye disease;Ciliopathy
Orphanet:2466	MASA syndrome	L1CAM	1	A X-linked, clinical subtype of L1 syndrome, characterized by mild to moderate intellectual disability, delayed development of speech, hypotonia progressing to spasticity or spastic paraplegia, adducted thumbs, and mild to moderate distension of the cerebral ventricles.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:560	Marshall syndrome	COL11A1	1	A malformation syndrome that is characterized by facial dysmorphism, severe hypoplasia of the nasal bones and frontal sinuses, ocular involvement, early-onset hearing loss, skeletal and anhidrotic ectodermal anomalies and short stature with spondyloepiphyseal dysplasia and early-onset osteoarthritis.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic bone disease;Rare genetic eye disease
Orphanet:587	Muir-Torre syndrome	MLH1;MSH2;MSH6	3	Muir-Torre syndrome (MTS) is a form of hereditary nonpolyposis colon cancer (HNPCC) characterized by cutaneous sebaceous tumors, keratoacanthomas and at least one visceral malignancy, most frequently gastrointestinal carcinoma.	Rare genetic tumor;Inherited cancer-predisposing syndrome
Orphanet:570	Moebius syndrome	PLXND1;REV3L	2	A very rare congenital cranial dysinnervation disorder characterized by complete or incomplete facial paralysis in association with bilateral palsy of the abducens nerve causing impairment of ocular abduction. The syndrome also includes various other congenital anomalies.	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic neurological disorder
Orphanet:179494	Obesity due to leptin receptor gene deficiency	LEPR	1	A rare, genetic, non-syndromic, obesity disease characterized by severe, early-onset obesity, associated with major hyperphagia and endocrine abnormalities, resulting from leptin receptor deficiency.	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility
Orphanet:1020	Early-onset autosomal dominant Alzheimer disease	ABCA7;TREM2;PSEN1;PSEN2;APP;SORL1;TOMM40	7	Early-onset autosomal dominant Alzheimer disease (EOAD) is a progressive dementia with reduction of cognitive functions. EOAD presents the same phenotype as sporadic Alzheimer disease (AD) but has an early age of onset, usually before 60 years old.	Rare genetic neurological disorder
Orphanet:54	X-linked recessive ocular albinism	GPR143	1	X-linked recessive ocular albinism (XLOA) is a rare disorder characterized by ocular hypopigmentation, foveal hypoplasia, nystagmus, photodysphoria, and reduced visual acuity in males.	Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:154	Familial isolated dilated cardiomyopathy	TAF1A;NEBL;PPCS;ABCC9;ACTC1;PSEN1;PSEN2;SCN5A;SDHA;SGCD;TAZ;TCAP;TNNI3;TNNT2;TPM1;TTN;CRYAB;CSRP3;DES;DMD;DSG2;FKTN;LDB3;DOLK;MYBPC3;MYH6;MYH7;RAF1;TMPO;TNNC1;VCL;ACTN2;FHL2;PLN;BAG3;RBM20;NEXN;TXNRD2;GATAD1;MYPN;LAMA4;PRDM16;ANKRD1	43	Familial isolated dilated cardiomyopathy is a rare, genetically heterogeneous cardiac disease characterized by dilatation leading to systolic and diastolic dysfunction of the left and/or right ventricles, causing heart failure or arrhythmia.	Rare genetic cardiac disease;Rare genetic neurological disorder
Orphanet:84	Fanconi anemia	RAD51;MAD2L2;BRCA1;XRCC2;RFWD3;BRCA2;BRIP1;ERCC4;FANCA;FANCB;FANCC;FANCD2;FANCE;FANCF;FANCG;FANCL;FANCM;FANCI;PALB2;RAD51C;SLX4;UBE2T	22	Fanconi anemia (FA) is a hereditary DNA repair disorder characterized by progressive pancytopenia with bone marrow failure, variable congenital malformations and predisposition to develop hematological or solid tumors.	Rare genetic developmental defect during embryogenesis;Inherited cancer-predisposing syndrome;Rare genetic hematologic disease;Rare genetic skin disease;Rare genetic bone disease;Rare genetic renal disease
Orphanet:816	Sjögren-Larsson syndrome	ALDH3A2	1	A rare neurocutaneous disorder caused by an inborn error of lipid metabolism and characterized by congenital ichthyosis, intellectual deficit, and spasticity.	Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic skin disease;Rare inborn errors of metabolism
Orphanet:821	Sotos syndrome	NSD1;SETD2;APC2	3	Sotos syndrome is a rare multisystemic genetic disorder characterized by a typical facial appearance, overgrowth of the body in early life with macrocephaly, and mild to severe intellectual disability.	Rare genetic developmental defect during embryogenesis;Inherited cancer-predisposing syndrome;Rare genetic bone disease;Rare genetic eye disease;Rare chromosomal anomaly
Orphanet:3204	Stormorken-Sjaastad-Langslet syndrome	ORAI1;STIM1	2	Stormorken-Sjaastad-Langslet syndrome is characterized by thrombocytopathy, asplenia, miosis, muscle fatigue, migraine, dyslexia, and ichthyosis. It has been described in six members of one family. It is transmitted as an autosomal dominant trait.	Rare genetic hematologic disease;Rare genetic eye disease
Orphanet:3205	Sturge-Weber syndrome	GNAQ	1	Sturge-Weber syndrome (SWS) is a rare congenital neurocutaneous disorder characterized by facial capillary malformations and/or cerebral and ocular ipsilateral vascular malformations that result in variable degrees of ocular and neurological anomalies.	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic neurological disorder
Orphanet:3320	Thrombocytopenia-absent radius syndrome	RBM8A	1	Thrombocytopenia-absent radius (TAR) syndrome is a very rare congenital malformation syndrome characterized by bilateral radial aplasia and thrombocytopenia.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic hematologic disease
Orphanet:887	VACTERL/VATER association	HOXD13	1	VACTERL/VATER is an association of congenital malformations typically characterized by the presence of at least three of the following: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis
Orphanet:909	Cerebrotendinous xanthomatosis	CYP27A1	1	Cerebrotendinous xanthomatosis (CTX) is an anomaly of bile acid synthesis (see this term) characterized by neonatal cholestasis, childhood-onset cataract, adolescent to young adult-onset tendon xanthomata, and brain xanthomata with adult-onset neurologic dysfunction.	Rare genetic neurological disorder;Rare genetic eye disease;Rare inborn errors of metabolism;Rare genetic endocrine disease;Rare genetic skin disease;Rare genetic hepatic disease
Orphanet:3447	Weaver syndrome	EED;NSD1;EZH2;SUZ12	4	Weaver syndrome (WVS) is a rare, multisystem disorder characterized by tall stature, a typical facial appearance (hypertelorism, retrognathia) and variable intellectual disability. Additional features may include camptodactyly, soft doughy skin, umbilical hernia, and a low hoarse cry.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:1422	Chondrodysplasia-disorder of sex development syndrome	HHAT	1	Chondrodysplasia - disorder of sex development is an extremely rare disorder of sex development (see this term), reported in only two siblings (one terminated in pregnancy) to date, characterized by the clinical features of 46,XY complete gonadal dysgenesis (see this term; normal external female genitalia, lack of pubertal development, primary amenorrhea, and hypergonadotrophic hypogonadism) in association with severe dwarfism with generalized chondrodysplasia (bell-shaped thorax, micromelia, brachydactyly). Other reported features in the live sibling included eye anomalies (hypoplastic irides, myopia, coloboma of optic discs), dysmorphic features (deep-set eyes, upslanting palpebral fissures, puffy eyelids, large ears and mouth, mild prognathism), muscular hypoplasia, mild intellectual deficiency and severe microcephaly with cerebellar vermis hypoplasia. An autosomal recessive inheritance has been suggested.	Rare genetic gynecological and obstetrical diseases;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease;Rare genetic eye disease;Rare genetic bone disease
Orphanet:178469	Autosomal dominant non-syndromic intellectual disability	CLTC;CHAMP1;HIVEP2;KDM5B;SET;RAB11A;PPP3CA;KCNQ5;ZMYND11;STXBP1;CIC;CSNK2B;TCF4;SYNGAP1;KIRREL3;DOCK8;MBD5;GRIN2B;CDH15;KIF1A;GRIN1;DYNC1H1;CACNG2;EPB41L1;DEAF1;EEF1A2;CAMK2A;CAMK2B	28	NA	Rare genetic neurological disorder
Orphanet:178461	X-linked myopathy with postural muscle atrophy	FHL1	1	X-linked myopathy with postural muscle atrophy is a rare progressive muscular dystrophy characterized by an adult-onset scapulo-axio-peroneal myopathy. Clinical presentation includes shoulder girdle atrophy, scapular winging, axial muscular atrophy of postural muscles combined with a generalized hypertrophy. Typically, neck rigidity, rigid spine, Achilles tendon shortening, and respiratory insufficiency later in disease course are present.	Rare genetic neurological disorder
Orphanet:178464	Hereditary myopathy with early respiratory failure	TTN	1	NA	Rare genetic neurological disorder
Orphanet:178396	Hemorrhagic disease due to alpha-1-antitrypsin Pittsburgh mutation	SERPINA1	1	Hemorrhagic disease due to alpha-1-antitrypsin Pittsburg mutation is a rare, genetic, constitutional coagulation factor defect disorder characterized by a bleeding tendancy of variable severity due to methionine 358 to arginine replacement (Pittsburgh mutation) in the alpha-1-antitrypsin protein. Patients present with spontaneous hematomas, hematomas following minor trauma or surgery and, in female patients, ovarian hematomas after ovulation.	Rare genetic hematologic disease;Serpinopathy
Orphanet:178400	Distal myopathy with anterior tibial onset	DYSF	1	Distal myopathy with anterior tibial onset is a rare, genetic neuromuscular disease characterized by a progressive muscle weakness starting in the anterior tibial muscles, later involving lower and upper limb muscles, associated with an increased serum creatine kinase levels and absence of dysferlin on muscle biopsy. Patients become wheelchair dependent.	Rare genetic neurological disorder
Orphanet:62	Autosomal recessive limb-girdle muscular dystrophy type 2D	SGCA	1	A subtype of autosomal recessive limb-girdle muscular dystrophy characterized by childhood onset of progressive proximal weakness of the shoulder and pelvic girdle muscles, resulting in difficulty walking, scapular winging, calf hypertrophy and contractures of the Achilles tendon, which lead to a tiptoe gait pattern. Cardiac and respiratory involvement is rare.	Rare genetic cardiac disease;Rare genetic neurological disorder
Orphanet:178389	Osteopetrosis-hypogammaglobulinemia syndrome	TNFRSF11A	1	Osteopetrosis-hypogammaglobulinemia syndrome is an extremely rare primary bone dysplasia with increased bone density disorder characterized by severe osteoclast-poor osteopetrosis associated with hypogammaglobulinemia. Patients typically present infantile malignant osteopetrosis (manifesting with increased bone density, bone fractures, abnormal eye movements/visual loss, nystagmus), hematologic abnormalities with bone marrow failure (e.g. anemia, hepatosplenomegaly) and immunological deficiency (manifesting as recurrent respiratory infections) associated with reduced immunoglobulin levels due to impaired peripheral B cell differentiation.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic immune disease
Orphanet:178364	Syndromic microphthalmia type 5	OTX2	1	Syndromic microphthalmia, type 5 is characterized by the association of a range of ocular anomalies (anophthalmia, microphthalmia and retinal abnormalities) with variable developmental delay and central nervous system malformations.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:715	Glycogen storage disease due to muscle phosphorylase kinase deficiency	PHKA1;PHKG1	2	Glycogen storage disease due to muscle phosphorylase kinase (PhK) deficiency is a benign inborn error of glycogen metabolism characterized by exercise intolerance.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:348	Fructose-1,6-bisphosphatase deficiency	FBP1	1	Fructose-1,6-biphosphatase (FBP) deficiency is a disorder of fructose metabolism (see this term) characterized by recurrent episodes of fasting hypoglycemia with lactic acidosis, that may be life-threatening in neonates and infants.	Rare inborn errors of metabolism
Orphanet:178377	Osteosclerosis-developmental delay-craniosynostosis syndrome	LRP5	1	This newly described syndrome is characterized by osteosclerosis, developmental delay and craniosynostosis (see this term).	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:178345	Aromatase excess syndrome	CYP19A1	1	A rare, genetic endocrine disease characterized by increased levels of estrogen due to elevated extraglandular aromatase activity. Males present with heterosexual precocious puberty which manifests with pre- or peripubertal onset of gynecomastia, premature growth spurt, accelerated bone maturation resulting in decreased adult stature, and may present mild hypogonadotropic hypogonadism. Female patients may have isosexual precocious puberty or not have any manifestations at all.	Rare genetic endocrine disease;Rare genetic gynecological and obstetrical diseases
Orphanet:178355	Smith-McCort dysplasia	DYM;RAB33B	2	Smith-McCort dysplasia (SMC) is a rare spondylo-epi-metaphyseal dysplasia characterized by the clinical manifestations of coarse facies, short neck, short trunk dwarfism with barrel-shaped chest and rhizomelic limb shortening, as well as specific radiological features (i.e. generalized platyspondyly with double-humped vertebral end plates and iliac crests with a lace-like appearance) and normal intelligence. The clinical and skeletal features are similar to those seen in the allelic disorder Dyggve-Melchior-Clausen syndrome (DMC; see this term), but can be distinguished from this syndrome by the absence of intellectual deficiency and microcephaly in SMC.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:178338	UV-sensitive syndrome	ERCC6;ERCC8;UVSSA	3	NA	Rare genetic skin disease
Orphanet:178342	Inflammatory myofibroblastic tumor	TPM3;ALK;RANBP2;CLTC;CARS;TPM4	6	Inflammatory myofibroblastic tumor is a rare neoplastic lesion of the submucosal stroma, which can develop in any organ, often occurring in the lung, mesentery, omentum and the retroperitoneal region. It is histologically heterogenous, composed of spindle-shaped cells, myofibroblasts and inflammatory cells. It is usually benign, however local invasion, recurrence, malignant transformation with vascular invasion and metastases may occur. The presentation is nonspecific and depends on the organ involved. Some patients may present with paraneoplastic syndrome (fever, malaise, weight loss, anemia, thrombocytosis) or symptoms related to compression of adjacent organs, such as bowel obstruction.	
Orphanet:117	Behçet disease	IL10;HLA-B;FAS;UBAC2;IL23R;MEFV;STAT4;C4A;IL12A;TLR4;CCR1;KLRC4;IL12A-AS1;ERAP1	14	A rare, chronic, relapsing, multisystemic vasculitis characterized by mucocutaneous lesions, as well as articular, vascular, ocular and central nervous system manifestations.	
Orphanet:178509	Perry syndrome	DCTN1	1	A rare inherited neurodegenerative disorder characterized by rapidly progressive early-onset parkinsonism, central hypoventilation, weight loss, insomnia and depression.	Rare genetic neurological disorder
Orphanet:177926	Symptomatic form of hemophilia A in female carriers	F8	1	 gene (Xq28), encoding coagulation factor VIII.	Rare genetic hematologic disease
Orphanet:177929	Symptomatic form of hemophilia B in female carriers	F9	1	 gene (Xq28), encoding coagulation factor IX.	Rare genetic hematologic disease
Orphanet:177901	Prader-Willi syndrome due to paternal deletion of 15q11q13 type 1	SNORD115@;SNRPN;MAGEL2;NDN;OCA2;SNORD116@	6	NA	NA
Orphanet:423	Malignant hyperthermia of anesthesia	RYR1;CACNA1S	2	Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane and the depolarizing muscle relaxant succinylcholine, and rarely, to stresses such as vigorous exercise and heat.	Rare genetic neurological disorder
Orphanet:177904	Prader-Willi syndrome due to paternal deletion of 15q11q13 type 2	SNORD115@;SNRPN;MAGEL2;NDN;OCA2;SNORD116@	6	NA	NA
Orphanet:177907	Prader-Willi syndrome due to translocation	SNRPN	1	NA	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility;Rare genetic developmental defect during embryogenesis
Orphanet:177910	Prader-Willi syndrome due to imprinting mutation	SNORD115@;SNRPN;MAGEL2;NDN;SNORD116@	5	NA	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility;Rare genetic developmental defect during embryogenesis
Orphanet:388	Hirschsprung disease	RET;ECE1;EDN3;EDNRB;GDNF;NRTN;SEMA3C;SEMA3D	8	Hirschsprung disease (HSCR) is a congenital intestinal motility disorder that is characterized by signs of intestinal obstruction due to the presence of an aganglionic segment of variable extent in the terminal part of the colon.	Rare genetic gastroenterological disease
Orphanet:178333	Åland Islands eye disease	CACNA1F	1	An X-linked recessive retinal disease characterized by fundus hypopigmentation, decrased visual acuity, nystagmus, astigmatism, progressive axial myopia, defective dark adaptation and protanopia.	Rare genetic eye disease
Orphanet:760	Purine nucleoside phosphorylase deficiency	PNP	1	Purine nucleoside phosphorylase (PNP) deficiency is a disorder of purine metabolism characterized by progressive immunodeficiency leading to recurrent and opportunistic infections, autoimmunity and malignancy as well as neurologic manifestations.	Rare inborn errors of metabolism;Rare genetic immune disease
Orphanet:178330	OBSOLETE: Heinz body anemia	HBB	1	NA	NA
Orphanet:270	Oculopharyngeal muscular dystrophy	PABPN1	1	Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset progressive myopathy characterized by progressive eyelid ptosis, dysphagia, dysarthria and proximal limb weakness.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:244	Primary ciliary dyskinesia	DNAH1;PIH1D3;DNAJB13;TTC25;MCIDAS;OFD1;DNAH11;DNAH5;DNAI1;NME8;DNAI2;DNAAF2;RSPH9;RSPH4A;DNAAF1;CCDC39;CCDC40;DNAL1;DNAAF3;CCDC103;DNAAF5;HYDIN;LRRC6;CCDC114;DRC1;ARMC4;DNAAF4;RSPH1;ZMYND10;CFAP298;CCDC65;SPAG1;CCNO;CCDC151;RSPH3;GAS8;RPGR;STK36;CFAP300	39	A rare, genetically heterogeneous, primarily respiratory disorder characterized by chronic upper and lower respiratory tract disease. Approximately half of the patients have an organ laterality defect (situs inversus totalis or situs ambiguus/heterotaxy).	Ciliopathy;Genetic infertility
Orphanet:178307	Reticulate acropigmentation of Kitamura	ADAM10	1	A rare, genetic, hyperpigmentation of the skin disease characterized by childhood to adulthood-onset of reticulate, slightly depressed, sharply demarcated, brown, macular skin lesions without hypopigmentation, affecting the dorsa of the hands and feet, and, occasionally, progressing to involve limbs, neck, forehead and/or trunk. Interrupted dermatoglyphics and palmoplantar pits may be additionally observed. Histologically, hyperpigmented lesions show slightly elongated and thinned rete ridges, mild hyperkeratosis without parakeratosis and absence of incontinentia pigmenti.	Rare genetic skin disease
Orphanet:805	Tuberous sclerosis complex	TSC1;TSC2	2	Tuberous sclerosis complex (TSC) is a neurocutaneous disorder characterized by multisystem hamartomas and associated with neuropsychiatric features.	Rare genetic neurological disorder;Inherited cancer-predisposing syndrome;Rare genetic renal disease;Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:178145	Moderate multiminicore disease with hand involvement	RYR1	1	NA	Rare genetic neurological disorder
Orphanet:791	Retinitis pigmentosa	SCAPER;IFT88;REEP6;ARHGEF18;AHI1;AGBL5;ABCA4;PRCD;PRPF3;PRPF31;PRPF8;PRPH2;RDH12;RGR;RHO;RLBP1;ROM1;RP1;RP2;RP9;RPE65;RPGR;SAG;BBS2;BEST1;CA4;CERKL;TTC8;TULP1;USH2A;CLRN1;CNGA1;CRB1;CRX;ARL6;FSCN2;HGSNAT;IMPDH1;MERTK;NR2E3;NRL;OFD1;PDE6A;PDE6B;SEMA4A;CNGB1;TOPORS;PROM1;LRAT;EYS;IDH3B;SPATA7;GUCA1B;KLHL7;SNRNP200;PCARE;PDE6G;IMPG2;FAM161A;ZNF513;CDHR1;DHDDS;PRPF6;MAK;RBP3;C8ORF37;IFT140;ZNF408;ARL2BP;NEK2;IFT172;TUB;KIZ;SLC7A14;PRPF4;AHR;ARL3;POMGNT1	78	Retinitis pigmentosa (RP) is an inherited retinal dystrophy leading to progressive loss of the photoreceptors and retinal pigment epithelium and resulting in blindness usually after several decades.	Rare genetic eye disease;Ciliopathy
Orphanet:2131	Alternating hemiplegia of childhood	CACNA1A;ATP1A2;ATP1A3;SLC1A3	4	A rare, genetic, neurodevelopmental disorder characterized by early-onset of recurrent, transient episodes of hemiplegia (including quadriplegia), which typically disappear upon sleep.	Rare genetic neurological disorder
Orphanet:713	Glycogen storage disease due to phosphoglycerate kinase 1 deficiency	PGK1	1	A rare inborn errors of metabolism characterized by variable combinations of non-spherocytic hemolytic anemia, myopathy, and various central nervous system abnormalities.	Rare inborn errors of metabolism;Rare genetic neurological disorder;Rare genetic hematologic disease
Orphanet:57	Glycogen storage disease due to aldolase A deficiency	ALDOA	1	Glycogen storage disease due to aldolase A deficiency is an extremely rare glycogen storage disease (see this term) characterized by hemolytic anemia with or without myopathy or intellectual deficit. Myopathy can be severe enough to result in fatal rhabdomyolysis in some patients. A family with episodic rhabdomyolysis (triggered by fever) without hemolytic anemia has recently been reported.	Rare inborn errors of metabolism;Rare genetic hematologic disease
Orphanet:2334	Autosomal dominant keratitis	PAX6	1	Hereditary keratitis is characterised by opacification and vascularisation of the cornea, often associated with macula hypoplasia.	Rare genetic eye disease
Orphanet:46	Adenylosuccinate lyase deficiency	ADSL	1	A disorder of purine metabolism characterized by intellectual disability, psychomotor delay and/or regression, seizures, and autistic features.	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:3166	Sialuria	GNE	1	Sialuria is an extremely rare metabolic disorder described in fewer than 10 patients to date and characterized by variable signs and symptoms, mostly in infancy, including transient failure to thrive, slightly prolonged neonatal jaundice, equivocal or mild hepatomegaly, microcytic anemia, frequent upper respiratory infections, gastroenteritis, dehydration and flat and coarse facies. Learning difficulties and seizures may occur in childhood.	Rare inborn errors of metabolism
Orphanet:2882	Sitosterolemia	ABCG5;ABCG8	2	 (2p21) genes.	Rare inborn errors of metabolism;Rare genetic endocrine disease
Orphanet:900	Granulomatosis with polyangiitis	HLA-DPA1;HLA-DPB1;CTLA4;PTPN22;PRTN3	5	A rare anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis characterized by necrotizing inflammation of small and medium vessels (capillaries, venules and arterioles), resulting in tissue ischemia.	
Orphanet:171695	Parkinsonian-pyramidal syndrome	SNCA;FBXO7	2	Parkinsonian-pyramidal syndrome is a rare, genetic, neurological disorder characterized by the association of both parkinsonian (i.e. bradykinesia, rigidity and/or rest tremor) and pyramidal (i.e. increased reflexes, extensor plantar reflexes, pyramidal weakness or spasticity) manifestations, which vary according to the underlying associated disease (e.g. neurodegenerative disease, inborn errors of metabolism).	Rare genetic neurological disorder
Orphanet:134	Beta-ketothiolase deficiency	ACAT1	1	A rare organic aciduria affecting ketone body metabolism and the catabolism of isoleucine and characterized by intermittent ketoacidotic episodes associated with vomiting, dyspnea, tachypnoea, hypotonia, lethargy and coma, with an onset during infancy or toddlerhood and usually ceasing by adolescence.	Rare inborn errors of metabolism
Orphanet:171700	Diffuse panbronchiolitis	MUCL3;MUC5B	2	Diffuse panbronchiolitis is a rare chronic inflammatory obstructive pulmonary disease primarily affecting the respiratory bronchioles throughout both lungs and inducing sinobronchial infection. Onset occurs in the second to fifth decade of life and manifests by chronic cough, exertional dyspnea, and sputum production. Most patients also have chronic paranasal sinusitis	
Orphanet:171703	Microcephaly-polymicrogyria-corpus callosum agenesis syndrome	DISC1;EOMES	2	Microcephaly-polymicrogyria-corpus callosum agenesis syndrome is a rare, genetic, central nervous system malformation syndrome characterized by marked prenatal-onset microcephaly, severe motor delay with hypotonia, bilateral polymicrogyria, corpus callosum agenesis, ventricular dilation, small cerebellum and early lethality.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:171706	Short stature-delayed bone age due to thyroid hormone metabolism deficiency	SECISBP2	1	Short stature-delayed bone age due to thyroid hormone metabolism deficiency is a rare, genetic congenital hypothyroidism disorder characterized by mild global developmental delay in childhood, short stature, delayed bone age, and abnormal thyroid and selenium levels in serum (high total and free T4 concentrations, low T3, high reverse T3, normal to high TSH, decreased selenium). Intellectual disability, primary infertility, hypotonia, muscle weakness, and impaired hearing have also been reported.	Rare genetic endocrine disease
Orphanet:171709	Male infertility due to globozoospermia	GOPC;SPATA16;DPY19L2;PICK1	4	Male infertility due to globozoospermia is a male infertility due to sperm disorder characterized by the presence, in sperm, of a large majority of round-headed spermatozoa that lack the acrosome and have an aberrant nuclear membrane and midpiece defects. The acrosomeless spermatozoa is not able to penetrate the zona pellucida and thus fertilization failures, even with intracytoplasmic sperm injection, are frequent.	Genetic infertility
Orphanet:171714	Amish infantile epilepsy syndrome	ST3GAL5	1	NA	Rare genetic skin disease;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:171723	White sponge nevus	KRT4;KRT13	2	White sponge nevus (WSN) is a rare and autosomal dominant genetic disease in which the oral mucosa is white or greyish, thickened, folded, and spongy. The onset is early in life, and both sexes are affected equally. Other common sites include the tongue, floor of the mouth, and alveolar mucosa.	Rare genetic tumor
Orphanet:171680	Lissencephaly due to TUBA1A mutation	TUBA1A	1	Lissencephaly (LIS) due to TUBA1A mutation is a congenital cortical development anomaly due to abnormal neuronal migration involving neocortical and hippocampal lamination, corpus callosum, cerebellum and brainstem. A large clinical spectrum can be observed, from children with severe epilepsy and intellectual and motor deficit to cases with severe cerebral dysgenesis in the antenatal period leading to pregnancy termination due to the severity of the prognosis.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:171690	Metabolic myopathy due to lactate transporter defect	SLC16A1	1	Metabolic myopathy due to lactate transporter defect is a rare metabolic myopathy characterized by muscle cramping and/or stiffness after exercise (especially during heat exposure), post-exertional rhabdomyolysis and myoglobinuria, and elevation of serum creatine kinase.	Rare genetic neurological disorder
Orphanet:171863	Autosomal dominant spastic paraplegia type 42	SLC33A1	1	A pure form of hereditary spastic paraplegia characterized by slowly progressive spastic paraplegia of lower extremities with an age of onset ranging from childhood to adulthood and patients presenting with spastic gait, increased tendon reflexes in lower limbs, extensor plantar response, weakness and atrophy of lower limb muscles and, in rare cases, pes cavus. No abnormalities are noted on magnetic resonance imaging.	Rare genetic neurological disorder
Orphanet:171871	Renal pseudohypoaldosteronism type 1	NR3C2	1	Renal pseudohypoaldosteronism type 1 (renal PHA1) is a mild form of primary mineralocorticoid resistance restricted to the kidney.	Rare genetic renal disease
Orphanet:171866	Spondyloepimetaphyseal dysplasia, aggrecan type	ACAN	1	Spondyloepimetaphyseal dysplasia, aggrecan type is a new form of skeletal dysplasia characterized by severe short stature, facial dysmorphism and characteristic radiographic findings.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:171881	Cap myopathy	MYPN;TPM2;TPM3	3	Cap myopathy is a very rare congenital myopathy presenting a weakness of facial and respiratory muscles associated with craniofacial and thoracic deformities, as well as weakness of limb proximal and distal muscles. Onset is at birth or in childhood, weakness progression is slow but may lead to a severe and even fatal prognosis.	Rare genetic neurological disorder
Orphanet:2512	Autosomal recessive primary microcephaly	CIT;NCAPD3;COPB2;KIF14;TAF13;PYCR2;CDK5RAP2;CENPJ;ASPM;MCPH1;STIL;WDR62;CEP152;CEP63;CEP135;KNL1;PHC1;CDK6;SASS6;MFSD2A;ANKLE2	21	Autosomal recessive primary microcephaly (MCPH) is a rare genetically heterogeneous disorder of neurogenic brain development characterized by reduced head circumference at birth with no gross anomalies of brain architecture and variable degrees of intellectual impairment.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:171876	Generalized pseudohypoaldosteronism type 1	SCNN1A;SCNN1B;SCNN1G	3	Generalized pseudohypoaldosteronism type 1 (generalized PHA1) is a severe form of primary mineralocorticoid resistance with systemic involvement and salt loss in multiple organs.	Rare genetic renal disease
Orphanet:797	Sarcoidosis	BTNL2;HLA-DRB1	2	Sarcoidosis is a multisystemic disorder of unknown cause characterized by the formation of immune granulomas in involved organs.	Rare genetic endocrine disease
Orphanet:171829	6q16 microdeletion syndrome	SIM1	1	Deletion 6q16 syndrome is a Prader-Willi like syndrome characterized by obesity, hyperphagia, hypotonia, small hands and feet, eye/vision anomalies, and global developmental delay.	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility;Rare genetic developmental defect during embryogenesis;Rare chromosomal anomaly
Orphanet:171851	MEDNIK syndrome	AP1S1	1	MEDNIK syndrome, previously known as Erythrokeratodermia Variabilis type 3 (EKV3), is characterized by intellectual deficit, enteropathy, sensorineural hearing loss, peripheral neuropathy, lamellar and erythrodermic ichthyosis, and keratodermia (MEDNIK stands for Mental retardation, Enteropathy, Deafness, peripheral Neuropathy, Ichtyosis, Keratodermia).	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder;Rare genetic skin disease;Rare inborn errors of metabolism
Orphanet:171848	Polyneuropathy-hearing loss-ataxia-retinitis pigmentosa-cataract syndrome	ABHD12	1	Fiskerstrand type peripheral neuropathy is a slowly-progressive Refsum-like disorder associating signs of peripheral neuropathy with late-onset hearing loss, cataract and pigmentary retinopathy that become evident during the third decade of life.	Genetic otorhinolaryngologic disease;Rare genetic eye disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:3303	Tetralogy of Fallot	ZFPM2;GATA4;JAG1;NKX2-5;GATA5;GJA5;NKX2-6;GDF1;CITED2;GATA6;TBX1	11	Tetralogy of Fallot is a congenital cardiac malformation that consists of an interventricular communication, also known as a ventricular septal defect, obstruction of the right ventricular outflow tract, override of the ventricular septum by the aortic root, and right ventricular hypertrophy.	
Orphanet:200418	Immunodeficiency with factor I anomaly	CFI	1	), typically manifesting as otitis, sinusitis, bronchitis, pneumonia, and/or meningitis. Autoimmune disease (e.g. systemic lupus erythematosus, glomerulonephritis) and atypical hemolytic uremic syndrome may be associated. Laboratory serum analysis reveals, in addition to diminished or undetectable complement factor I, variably decreased complement C3, complement factor B and complement factor H.	Rare genetic immune disease
Orphanet:730	Autosomal dominant polycystic kidney disease	GANAB;PKD1;PKD2;BICC1	4	NA	Rare genetic renal disease;Genetic infertility
Orphanet:200421	Immunodeficiency with factor H anomaly	CFH	1	), renal impairment and/or autoimmune diseases, typically manifesting with otitis media, bronchitis, meningitis, and/or septicemia, as well as hematuria/proteinuria, asthma, nephrotic syndrome, hemolytic uremic syndrome, glomerulonephritis, and/or systemic lupus erythematosus. Laboratory serum analysis reveals, in addition to factor H deficiency, decreased complement factor B, properin, complement C3 and terminal complement components.	Rare genetic immune disease
Orphanet:486	Autosomal dominant severe congenital neutropenia	TCIRG1;ELANE;GFI1	3	A rare primary immunodeficiency disorder characterized by autosomal dominant inheritance, absolute neutrophil counts below 0.5x10E9/L in the peripheral blood (on three separate occasions over a six month period), granulopoiesis maturation arrest at the promyelocyte/myelocyte stage and early-onset, severe, recurrent bacterial infections.	Rare genetic immune disease
Orphanet:98	Autosomal recessive spastic ataxia of Charlevoix-Saguenay	SACS	1	Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neurodegenerative disorder characterised by early-onset cerebellar ataxia with spasticity, a pyramidal syndrome and peripheral neuropathy.	Rare genetic neurological disorder
Orphanet:330	Congenital factor XII deficiency	F12	1	A rare, autosomal recessive systemic dysfunction of the hemostatic pathway, that is due to a defect in the coagulation factor XII (FXII or Hageman factor), and is either asymptomatic or characterized by a prolonged activated partial thromboplastin time and an increased risk for thromboembolism. FXII deficiency is strongly associated with primary recurrent abortions.	Rare genetic hematologic disease
Orphanet:199340	Muscular dystrophy, Selcen type	BAG3	1	Selcen type muscular dystrophy is characterized by progressive limb and axial muscle weakness associated with cardiomyopathy and severe respiratory insufficiency during adolescence. The disease manifests during childhood and progresses rapidly.	Rare genetic neurological disorder
Orphanet:199337	Pancreatic insufficiency-anemia-hyperostosis syndrome	COX4I2	1	This syndrome is characterized by exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic gastroenterological disease;Rare inborn errors of metabolism;Rare genetic hematologic disease
Orphanet:234	Dubin-Johnson syndrome	ABCC2	1	Dubin-Johnson syndrome (DJS) is a benign, inherited liver disorder characterized clinically by chronic, predominantly conjugated, hyperbilirubinemia and histopathologically by black-brown pigment deposition in parenchymal liver cells.	Rare genetic hepatic disease;Rare inborn errors of metabolism
Orphanet:199348	Thiamine-responsive encephalopathy	SLC19A3	1	Thiamine-responsive encephalopathy is a Wernicke-like encephalopathy (see this term) characterized by seizures responsive to high doses of thiamine.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:3287	Takayasu arteritis	HLA-B;IL12B;MLX	3	A rare predominantly large-vessel vasculitis that is characterized by affected aorta and its major branches, but also other large vessels, causing stenosis, occlusion, or aneurysm.	
Orphanet:199343	EAST syndrome	KCNJ10	1	SeSAME syndrome is characterized by seizures, sensorineural deafness, ataxia, intellectual deficit, and electrolyte imbalance (hypokalemia, metabolic alkalosis, and hypomagnesemia).	Genetic otorhinolaryngologic disease;Rare genetic renal disease;Rare genetic neurological disorder
Orphanet:199326	Isolated autosomal dominant hypomagnesemia, Glaudemans type	KCNA1	1	Isolated autosomal dominant hypomagnesemia, Glaudemans type (IADHG) is a form of familial primary hypomagnesemia (FPH, see this term), characterized by low serum magnesium (Mg) values but normal urinary Mg values. The typical clinical features are recurrent muscle cramps, episodes of tetany, tremor, and muscle weakness, especially in distal limbs. The disease is potentially fatal.	Rare genetic renal disease;Rare inborn errors of metabolism
Orphanet:199332	Endocrine-cerebro-osteodysplasia syndrome	ICK	1	Endocrine-cerebro-osteodysplasia (ECO) syndrome is characterized by various anomalies of the endocrine, cerebral, and skeletal systems resulting in neonatal mortality.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2665	Congenital mesoblastic nephroma	ETV6;NTRK3	2	NA	
Orphanet:199329	Congenital myopathy, Paradas type	DYSF	1	Paradas type congenital myopathy is an early-onset form of dysferlinopathy presenting with postnatal hypotonia, weakness in the proximal lower limbs and neck flexor muscles at birth and delayed motor development.	Rare genetic neurological disorder
Orphanet:3463	Wolfram syndrome	WFS1;CISD2	2	A rare, genetic, endocrine disorder characterized by type I diabetes mellitus (DM), diabetes insipidus (DI), sensorineural deafness (D), bilateral optical atrophy (OA) and neurological signs.	Genetic otorhinolaryngologic disease;Rare genetic eye disease;Rare genetic endocrine disease
Orphanet:199354	CARASIL	HTRA1	1	CARASIL is a hereditary cerebral small vessel disease characterized by early-onset gait disturbances, premature scalp alopecia, ischemic stroke, acute mid to lower back pain and progressive cognitive disturbances leading to severe dementia.	Rare genetic neurological disorder
Orphanet:356	Gerstmann-Straussler-Scheinker syndrome	PRNP	1	 gene) and marked by particular multicentric amyloid plaques in the brain.	Rare genetic neurological disorder
Orphanet:199351	Adult-onset dystonia-parkinsonism	PLA2G6	1	A rare neurodegenerative disease usually presenting before the age of 30 and which is characterized by dystonia, L-dopa-responsive parkinsonism, pyramidal signs and rapid cognitive decline.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:466	Fatal familial insomnia	PRNP	1	Fatal familial insomnia (FFI) is a very rare form of prion disease (see this term) characterized by subacute onset of insomnia showing as a reduced overall sleep time, autonomic dysfunction, and motor disturbances.	Rare genetic neurological disorder
Orphanet:199285	Hereditary hypercarotenemia and vitamin A deficiency	BCO1	1	Hereditary hypercarotenemia and vitamin A deficiency is an extremely rare metabolic disorder characterized clinically by skin discoloration, elevated levels of carotene and low levels of vitamin A described in fewer than 5 patients to date.	Rare inborn errors of metabolism
Orphanet:2102	GTP cyclohydrolase I deficiency	GCH1	1	GTP-cyclohydrolase I deficiency, an autosomal recessive genetic disorder, is one of the causes of malignant hyperphenylalaninemia due to tetrahydrobiopterin deficiency. Not only does tetrahydrobiopterin deficiency cause hyperphenylalaninemia, it is also responsible for defective neurotransmission of monoamines because of malfunctioning tyrosine and tryptophan hydroxylases, both tetrahydrobiopterin-dependent hydroxylases.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:3002	Immune thrombocytopenic purpura	FCGR2C	1	100,000/microL), in the absence of any underlying disorder that may be associated with thrombocytopenia.	
Orphanet:199318	15q13.3 microdeletion syndrome	CHRNA7	1	15q13.3 microdeletion (microdel15q13.3) syndrome is characterized by a wide spectrum of neurodevelopmental disorders with no or subtle dysmorphic features.	Rare genetic developmental defect during embryogenesis;Rare chromosomal anomaly;Rare genetic neurological disorder
Orphanet:274	Bernard-Soulier syndrome	GP1BA;GP1BB;GP9	3	Bernard Soulier syndrome (BSS) is an inherited platelet disorder characterized by mild to severe bleeding tendency , macrothrombocytopenia and absent ristocetin-induced platelet agglutination.	Rare genetic hematologic disease
Orphanet:199302	Isolated cleft lip	TP63;IRF6;NECTIN1;MSX1	4	Isolated cleft lip is a fissure type embryopathy extending from the upper lip to the nasal base.	
Orphanet:1195	Congenital atransferrinemia	TF	1	Congenital atransferrinemia is a very rare hematologic disease caused by a transferrin (TF) deficiency and characterized by microcytic, hypochromic anemia (manifesting with pallor, fatigue and growth retardation) and iron overload, and that can be fatal if left untreated.	Rare inborn errors of metabolism;Rare genetic hematologic disease
Orphanet:199306	Cleft lip/palate	ARHGAP29;TP63;BMP4;NECTIN1;CDH1;IRF6;MSX1;DLG1;DLX4	9	Cleft lip and palate is a fissure type embryopathy extending across the upper lip, nasal base, alveolar ridge and the hard and soft palate.	
Orphanet:926	Acatalasemia	CAT	1	A rare congenital disorder resulting from a deficiency in erythrocyte catalase, an enzyme responsible for the breakdown of hydrogen peroxide.	Rare inborn errors of metabolism
Orphanet:199296	Congenital isolated ACTH deficiency	TBX19	1	NA	Rare genetic endocrine disease
Orphanet:1675	Dihydropyrimidine dehydrogenase deficiency	DPYD	1	NA	Rare inborn errors of metabolism
Orphanet:976	Adenine phosphoribosyltransferase deficiency	APRT	1	A rare genetic nephropathy secondary to a disorder of purine metabolism characterized by the formation and hyperexcretion of 2,8-dihydroxyadenine (2,8-DHA) in urine, causing urolithiasis and crystalline nephropathy.	Rare inborn errors of metabolism;Rare genetic renal disease
Orphanet:189427	Cushing syndrome due to macronodular adrenal hyperplasia	GNAS;ARMC5	2	A rare cause of Cushing syndrome (CS) characterized by nodular enlargement of both adrenal glands (multiple nodules above 1 cm in diameter) that produce excess cortisol and features of adrenocorticotropic hormone (ACTH) independent CS.	Rare genetic endocrine disease;Genetic infertility
Orphanet:3129	Sarcosinemia	SARDH	1	Sarcosinemia is a metabolic disorder characterized by an increased concentration of sarcosine in plasma and urine due to sarcosine dehydrogenase deficiency.	Rare inborn errors of metabolism
Orphanet:415	Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome	SLC25A15	1	A rare, genetic disorder of urea cycle metabolism characterized by either a neonatal-onset with manifestations of lethargy, poor feeding, vomiting and tachypnea or, more commonly, presentations in infancy, childhood or adulthood with chronic neurocognitive deficits, acute encephalopathy and/or coagulation defects or other chronic liver dysfunction.	Rare inborn errors of metabolism
Orphanet:13	6-pyruvoyl-tetrahydropterin synthase deficiency	PTS	1	6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency is one of the causes of malignant hyperphenylalaninemia due to tetrahydrobiopterin deficiency. Not only does tetrahydrobiopterin deficiency cause hyperphenylalaninemia, it is also responsible for defective neurotransmission of monoamines because of malfunctioning tyrosine and tryptophan hydroxylases, both tetrahydrobiopterin-dependent hydroxylases.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:171	Primary sclerosing cholangitis	GPR35;MST1;TCF4	3	Primary sclerosing cholangitis (PSC) is a rare, slowly progressive liver disease characterized by inflammation and destruction of the intra- and/or extra-hepatic bile ducts that lead to cholestasis, liver fibrosis, liver cirrhosis and ultimately liver failure.	
Orphanet:199247	Corticosteroid-binding globulin deficiency	SERPINA6	1	Corticosteroid-binding globulin deficiency is a rare, genetic, adrenal disease characterized by diminished corticosteroid-binding capacity associated with normal or low plasma corticosteroid-binding globulin concentration and reduced total plasma cortisol levels. Patients typically present chronic pain, fatigue and hypo/hypertension.	Rare genetic endocrine disease;Serpinopathy
Orphanet:199241	Pulmonary capillary hemangiomatosis	EIF2AK4	1	NA	Rare genetic respiratory disease
Orphanet:17	Fatal infantile lactic acidosis with methylmalonic aciduria	SUCLG1	1	Fatal infantile lactic acidosis with methylmalonic aciduria is a rare neurometabolic disease characterized by infantile onset of severe encephalomyopathy, lactic acidosis and elevated methylmalonic acid urinary excretion. Clinically it manifests with severe psychomotor delay, hypotonia, failure to thrive, feeding difficulties and dystonia. Epilepsy and multiple congenital anomalies may be associated.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic gastroenterological disease;Rare genetic neurological disorder
Orphanet:189466	Familial isolated hypoparathyroidism due to impaired PTH secretion	PTH;AIRE	2	NA	Rare genetic eye disease;Rare genetic endocrine disease
Orphanet:189439	Primary pigmented nodular adrenocortical disease	PRKAR1A;PDE11A;PDE8B;PRKACA	4	Primary pigmented nodular adrenocortical disease (PPNAD) is a form of bilateral adrenocortical hyperplasia that is often associated with adrenocorticotrophin hormone (ACTH) independent Cushing syndrome (see this term) and is characterized by small to normal sized adrenal glands containing multiple small cortical pigmented nodules (less than 1 cm in diameter).	Rare genetic endocrine disease
Orphanet:3006	Pyridoxine-dependent epilepsy	ALDH7A1;SLC13A5;PLPBP	3	A rare neurometabolic disease characterized by recurrent intractable seizures in the prenatal, neonatal and postnatal period that are resistant to anti-epileptic drugs (AEDs) but that are responsive to pharmacological dosages of pyridoxine (vitamin B6).	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:3111	Rotor syndrome	SLCO1B1;SLCO1B3	2	A benign, inherited liver disorder characterized by chronic, predominantly conjugated, nonhemolytic hyperbilirubinemia with normal liver histology.	Rare genetic hepatic disease;Rare inborn errors of metabolism
Orphanet:2382	Lennox-Gastaut syndrome	CUX2;SCN1A;MAPK10;CHD2;DNM1;GABRB3	6	A rare syndrome that belongs to the group of severe childhood epileptic encephalopathies.	Rare genetic neurological disorder
Orphanet:1934	Early infantile epileptic encephalopathy	SCN2A;CDKL5;STXBP1;ARX;CASK;PNKP;GNAO1;PIGQ;SIK1;SLC25A22;KCNA1;PIGP	12	A severe form of age-related epileptic encephalopathies characterized by the onset of tonic spasms within the first 3 months of life that can be generalized or lateralized, independent of the sleep cycle, and that can occur hundreds of times per day, leading to psychomotor impairment and death.	Rare genetic neurological disorder
Orphanet:1942	Myoclonic-astastic epilepsy	CHD2;SLC6A1	2	A rare epilepsy syndrome of childhood characterized by the occurrence of multiple different seizure types including myoclonic-astatic, generalized tonic-clonic and absence seizures, usually in previously healthy children.	Rare genetic neurological disorder
Orphanet:1935	Early myoclonic encephalopathy	SLC25A22;SIK1	2	A rare disorder characterized clinically by the onset of fragmentary myoclonus appearing in the first month of life, often associated with erratic focal seizures and a suppression-burst EEG pattern.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:3451	West syndrome	NTRK2;STXBP1;SCN2A;CDKL5;ARX;PIGA;SPTAN1;PLCB1;GRIN2B;ST3GAL3;SIK1;GUF1;CNPY3	13	A rare disorder characterized by the association of clusters of axial spasms, psychomotor retardation and an hypsarrhythmic interictal EEG pattern. It is the most frequent type of epileptic encephalopathy. It may occur in otherwise healthy infants and in those with abnormal cognitive development.	Rare genetic neurological disorder
Orphanet:267	Autosomal recessive limb-girdle muscular dystrophy type 2A	CAPN3	1	A subtype of autosomal recessive limb girdle muscular dystrophy characterized by a variable age of onset of progressive, typically symmetrical and selective weakness and atrophy of proximal shoulder- and pelvic-girdle muscles (gluteus maximus, thigh adductors, and muscles of the posterior compartment of the limbs are most commonly affected) without cardiac or facial involvement. Clinical manifestations include exercise intolerance, a waddling gait, scapular winging and calf pseudo-hypertrophy.	Rare genetic neurological disorder
Orphanet:186	Primary biliary cholangitis	IL12RB1;SPIB;IL12A;IRF5;TNPO3;MMEL1;POU2AF1;TNFSF15	8	Primary biliary cholangitis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology characterized by injury of the intrahepatic bile ducts that may eventually lead to liver failure.	
Orphanet:1136	Arnold-Chiari malformation type II	FUZ	1	A rare, central nervous system malformation characterized by caudal displacement of the cerebellum, pons, medulla and fourth ventricle through the foramen magnum into the spinal canal, and is typically associated with myelomeningocele. Variable other central nervous system abnormalities might be present (partial or complete agenesis of the corpus callosum, a small fourth ventricle, obstructive hydrocephalus, falx and tentorium defects, and polygyria). Symptoms include hypotonia, apnea with cyanosis, dysphagia, opisthotonus, nystagmus, spasticity, ataxia, and occipital headache.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:397	Giant cell arteritis	PTPN22	1	Giant cell arteritis (GCA) is a large vessel vasculitis predominantly involving the arteries originating from the aortic arch and especially the extracranial branches of the carotid arteries.	
Orphanet:2398	Multiple symmetric lipomatosis	MFN2	1	A rare subcutaneous tissue disease characterized by growth of symmetric non-encapsulated masses of adipose tissue mostly around the face and neck, with variable clinical repercussions (e.g. reduced neck mobility, compression of respiratory structures).	Rare genetic skin disease
Orphanet:131	Budd-Chiari syndrome	F5;JAK2	2	Budd-Chiari syndrome (BCS) is caused by obstruction of hepatic venous outflow involving either the hepatic veins or the terminal segment of the inferior vena cava.	
Orphanet:654	Nephroblastoma	BRCA2;GPC3;TRIM28;TRIM28;REST;TRIP13;POU6F2;WT1;WT1;H19;DIS3L2	11	A rare malignant renal tumor, typically affecting the pediatric population, characterized by an abnormal proliferation of cells that resemble the kidney cells of an embryo (metanephroma), leading to the term embryonal tumor.	Rare genetic tumor
Orphanet:2587	Myeloperoxidase deficiency	MPO	1	A rare primary immunodeficiency due to a defect in innate immunity characterized by a marked decrease or absence of myeloperoxidase activity in neutrophils and monocytes. Clinically, most patients are asymptomatic. Occasionally, severe infectious complications may occur, particularly recurrent candida infections, being especially severe in the setting of comorbid diabetes mellitus.	Rare genetic immune disease
Orphanet:3389	Tuberculosis	SLC11A1	1	 that in most individuals is usually asymptomatic but that in at risk individuals (e.g. with diabetes or with HIV infection) can cause weakness, fever, weight loss, night sweat, and respiratory anomalies such as chronic cough, chest pain, hemoptysis or respiratory insufficiency.	Rare genetic endocrine disease
Orphanet:2897	Pityriasis rubra pilaris	CARD14	1	Pityriasis rubra pilaris is a rare chronic papulosquamous disorder of unknown etiology characterized by small follicular papules, scaly red-orange patches, and palmoplantar hyperkeratosis, which may progress to plaques or erythroderma. Although most of the cases are sporadic and acquired, a familial form of the disease exists.	Rare genetic skin disease
Orphanet:183707	Neutrophil immunodeficiency syndrome	RAC2	1	Neutrophil immunodeficiency syndrome is a primary immunodeficiency characterized by neutrophilia with severe neutrophil dysfunction, leukocytosis, a predisposition to bacterial infections and poor wound healing, including an absence of pus in infected areas.	Rare genetic immune disease
Orphanet:2312	Transient familial neonatal hyperbilirubinemia	UGT1A1	1	NA	
Orphanet:2314	Autosomal dominant hyper-IgE syndrome	STAT3	1	2000 IU/ml), recurring staphylococcal skin abscesses, and recurrent pneumonia with formation of pneumatoceles.	Rare genetic immune disease;Rare genetic skin disease
Orphanet:183678	Hermansky-Pudlak syndrome with neutropenia	AP3B1	1	Hermansky-Pudlak syndrome type 2 (HPS-2) is a type of Hermansky-Pudlak syndrome (HPS; see this term), a multi-system disorder characterized by oculocutaneous albinism, bleeding diathesis and neutropenia.	Rare genetic immune disease;Rare inborn errors of metabolism;Rare genetic eye disease;Rare genetic skin disease;Rare genetic hematologic disease
Orphanet:183675	Recurrent infections associated with rare immunoglobulin isotypes deficiency	IGHG2;IGKC	2	Deficiencies in immunoglobulin (Ig) isotypes (including: isolated IgG subclass deficiency, IgG sublcass deficiency with IgA deficiency and kappa chain deficiency) are primary immunodeficiencies that are often asymptomatic but can be characterized by recurrent, often pyogenic, sinopulmonary infections.	Rare genetic immune disease
Orphanet:2177	Hydranencephaly	NDE1	1	A rare cerebral malformation characterized by an almost or complete lack of cortex, specifically the cerebral hemispheres, with the cranium and meninges completely intact. In most cases, death occurs in utero or in the first weeks of life. Developmental delay, drug-resistant seizures, spastic diplegia, severe growth failure, deafness and blindness are typical.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:183713	Pyogenic bacterial infections due to MyD88 deficiency	MYD88	1	Pyogenic bacterial infection due to MyD88 deficiency is a primary immunodeficiency characterized by increased susceptibility to pyogenic bacterial infections, including invasive pneumococcal, invasive staphylococcal and pseudomonas disease.	Rare genetic immune disease
Orphanet:2380	Legg-Calvé-Perthes disease	COL2A1	1	A rare disorder characterized by uni- or bilateral avascular necrosis (AVN) of the femoral head in children.	Rare genetic bone disease
Orphanet:897	Waardenburg-Shah syndrome	SOX10;EDN3;EDNRB	3	Waardenburg-Shah syndrome (WSS), also known as Waardenburg syndrome type 4 (WS4) is characterized by the association of Waardenburg syndrome (sensorineural hearing loss and pigmentary abnormalities) and Hirschsprung disease (aganglionic megacolon).	Genetic otorhinolaryngologic disease;Rare genetic gastroenterological disease;Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:808	Seckel syndrome	ATR;CENPJ;PCNT;CEP152;RBBP8;ATRIP;TRAIP;PLK4;CENPE	9	Seckel syndrome is a type of microcephalic primordial dwarfism that is characterized by a proportionate dwarfism of prenatal onset, a severe microcephaly, a typical dysmorphic face (bird-like), and mild to severe intellectual disability.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic neurological disorder
Orphanet:3027	Caudal regression sequence	VANGL1;FUZ	2	Caudal regression sequence is a rare congenital malformation of the lower spinal segments associated with aplasia or hypoplasia of the sacrum and lumbar spine.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic neurological disorder
Orphanet:676	Hereditary chronic pancreatitis	CASR;PRSS1;CFTR;SPINK1;PRSS2;CTRC;CPA1	7	A rare gastroenterologic disease characterized by recurrent acute pancreatitis and/or chronic pancreatitis in at least 2 first-degree relatives, or 3 or more second-degree relatives in 2 or more generations, for which no predisposing factors are identified. This rare inherited form of pancreatitis leads to irreversible damage to both exocrine and endocrine components of the pancreas.	Rare genetic gastroenterological disease;Rare genetic endocrine disease
Orphanet:643	Giant axonal neuropathy	GAN	1	Giant axonal neuropathy (GAN) is a severe, slowly progressive neurodegenerative disorder characterized by progressive motor and sensory peripheral neuropathy, central nervous system involvement (including pyramidal and cerebellar signs), and characteristic kinky hair in most cases.	Rare genetic neurological disorder
Orphanet:634	Netherton syndrome	SPINK5	1	Netherton syndrome (NS) is a skin disorder characterized by congenital ichthyosiform erythroderma (CIE), a distinctive hair shaft defect (trichorrhexis invaginata; TI) and atopic manifestations.	Rare genetic immune disease;Rare genetic skin disease
Orphanet:140	Campomelic dysplasia	SOX9	1	Campomelic dysplasia is a very rare disorder characterised by a variable association of skeletal abnormalities (bowed and fragile long bones, pelvis and chest abnormalities, eleven rib pairs instead of the usual twelve), and extraskeletal abnormalities (facial dysmorphology, cleft palate, sexual ambiguity or sex reversal in two thirds of the affected boys, and brain, heart and kidney malformations).	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic gynecological and obstetrical diseases;Rare genetic urogenital disease;Rare genetic endocrine disease
Orphanet:2828	Young-onset Parkinson disease	SNCA;PINK1;UCHL1;HTRA2;PODXL;LRRK2;PRKN;PARK7;VPS13C;DNAJC6	10	Young-onset Parkinson disease (YOPD) is a form of Parkinson disease (PD), characterized by an age of onset between 21-45 years, rigidity, painful cramps followed by tremor, bradykinesia, dystonia, gait complaints and falls, and other non-motor symptoms. A slow disease progression and a more pronounced response to dopaminergic therapy are also observed in most YOPD forms.	Rare genetic neurological disorder
Orphanet:642	Hereditary sensory and autonomic neuropathy type 4	NTRK1	1	A rare hereditary sensory and autonomic neuropathy characterized by anhidrosis, insensitivity to pain, self-mutilating behavior and episodes of fever.	Rare genetic neurological disorder
Orphanet:627	Nance-Horan syndrome	NHS	1	Nance-Horan syndrome (NHS) is characterized by the association in male patients of congenital cataracts with microcornea, dental anomalies and facial dysmorphism.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:638	Neurofibromatosis-Noonan syndrome	MAP2K2;NF1	2	Neurofibromatosis-Noonan syndrome (NFNS) is a RASopathy and a variant of neurofibromatosis type 1 (NF1) characterized by the combination of features of NF1, such as café-au-lait spots, iris Lisch nodules, axillary and inguinal freckling, optic nerve glioma and multiple neurofibromas, and Noonan syndrome (NS), such as short stature, typical facial features (hypertelorism, ptosis, downslanting palpebral fissures, low-set posteriorly rotated ears with a thickened helix, and a broad forehead), congenital heart defects and unusual pectus deformity. As these three entities have significant phenotypic overlap, molecular genetic testing is often necessary for a correct diagnosis (such as when café-au-lait spots are present in patients diagnosed with NS).	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;RASopathy;Rare genetic cardiac disease
Orphanet:326	Congenital factor V deficiency	F5	1	Congenital factor V deficiency is an inherited bleeding disorder due to reduced plasma levels of factor V (FV) and characterized by mild to severe bleeding symptoms.	Rare genetic hematologic disease
Orphanet:526	Liddle syndrome	SCNN1B;SCNN1G	2	Liddle syndrome is a rare inherited form of hypertension characterized by severe early-onset hypertension associated with decreased plasmatic levels of potassium, renin and aldosterone.	Rare genetic renal disease
Orphanet:215	Congenital stationary night blindness	RHO;SAG;CABP4;CACNA1F;GNAT1;GRM6;NYX;PDE6B;CACNA2D4;TRPM1;SLC24A1;GPR179;LRIT3;GRK1;GNB3	15	#8805;-10.00 D)), nystagmus, strabismus, normal color vision and fundus abnormalities.	Rare genetic eye disease
Orphanet:342	Familial Mediterranean fever	MEFV	1	Familial Mediterranean fever (FMF) is an autoinflammatory disorder characterized by recurrent short episodes of fever and serositis resulting in pain in the abdomen, chest, joints and muscles.	Rare genetic immune disease;Rare genetic systemic or rheumatologic disease
Orphanet:180	Choroideremia	CHM	1	Choroideremia (CHM) is an X-linked chorioretinal dystrophy characterized by progressive degeneration of the choroid, retinal pigment epithelium (RPE) and retina.	Rare genetic eye disease
Orphanet:327	Congenital factor VII deficiency	F7	1	A rare, genetic, congenital vitamin K-dependant coagulation factor deficiency disorder characterized by decreased levels or absence of coagulation factor VII (FVII), resulting in bleeding diathesis of variable severity.	Rare genetic hematologic disease
Orphanet:373	Simpson-Golabi-Behmel syndrome	GPC3;GPC4	2	Simpson-Golabi-Behmel syndrome (SGBS, also referred to as SGBS type 1) is a rare X-linked multiple congenital anomalies syndrome, characterized by pre- and postnatal overgrowth, distinctive craniofacial features, variable congenital malformations, organomegaly and an increased tumor risk.	Rare genetic developmental defect during embryogenesis;Rare genetic renal disease;Inherited cancer-predisposing syndrome;Rare genetic neurological disorder
Orphanet:403	Familial hyperaldosteronism type I	CYP11B1;CYP11B2	2	Familial hyperaldosteronism type I (FH-I) is a rare heritable, glucocorticoid remediable form of primary aldosteronism (PA) characterized by early-onset hypertension, hyperaldosteronism, variable hypokalemia, low plasma renin activity (PRA), and abnormal production of 18-oxocortisol and 18-hydroxycortisol.	Rare genetic renal disease;Rare genetic endocrine disease
Orphanet:146	Differentiated thyroid carcinoma	EIF1AX;PPARG;RET;BRAF;CCDC6;TFG;TPR;TRIM24;TRIM27;TRIM33;ERC1;FOXE1;GOLGA5;HRAS;KRAS;NTRK1;PAX8;PCM1;ETV6;NKX2-1;ALK;NRAS;NTRK3;NCOA4;DIRC3;NDUFA13;GAS8-AS1;LPAR4	28	Differentiated thyroid carcinoma (DTC), also known as papillary or follicular thyroid carcinoma, is a slow-growing malignancy usually presenting in adults as an asymptomatic thyroid mass.	
Orphanet:1331	Familial prostate cancer	MSMB;SRD5A2;RNASEL;BRCA1;BRCA2;CHEK2;ELAC2;EPHB2;NBN;HNF1B;HOXB13;MSR1	12	Familial prostate cancer (FPC) is a malignant tumor of the prostate with an early onset. FPC is either asymptomatic or causes mictionary symptoms, erectile dysfunction, bone pain, venous compression and infectious or inflammatory syndrome (for the metastatic forms). It is also characterized by familial antecedents.	Rare genetic tumor
Orphanet:847	Alpha-thalassemia-X-linked intellectual disability syndrome	ATRX	1	X-linked alpha thalassaemia mental retardation (ATR-X) syndrome in males is associated with profound developmental delay, facial dysmorphism, genital abnormalities and alpha thalassaemia. Female carriers are usually physically and intellectually normal.	Rare genetic gynecological and obstetrical diseases;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease;Rare genetic neurological disorder;Rare genetic hematologic disease
Orphanet:2268	ICF syndrome	DNMT3B;ZBTB24;CDCA7;HELLS	4	The Immunodeficiency, Centromeric region instability, Facial anomalies syndrome (ICF) is a rare autosomal recessive disease characterized by immunodeficiency, although B cells are present, and by characteristic rearrangements in the vicinity of the centromeres (the juxtacentromeric heterochromatin) of chromosomes 1 and 16 and sometimes 9.	Rare genetic immune disease
Orphanet:475	Joubert syndrome	CEP120;PIBF1;TCTN2;AHI1;TMEM67;MKS1;ARL13B;INPP5E;TCTN1;B9D1;TMEM237;CEP41;CPLANE1;CSPP1;KIAA0586;CEP104;KIAA0556;ARMC9;HYLS1;ARL3	20	Joubert syndrome (JS) is characterized by congenital malformation of the brainstem and agenesis or hypoplasia of the cerebellar vermis leading to an abnormal respiratory pattern, nystagmus, hypotonia, ataxia, and delay in achieving motor milestones.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:392	Holt-Oram syndrome	TBX5	1	A genetic syndrome with limb reduction defects characterized by skeletal abnormalities of the upper limbs and mild-to-severe congenital cardiac defects.	Rare genetic developmental defect during embryogenesis;Rare genetic cardiac disease;Rare genetic bone disease
Orphanet:86	Familial abdominal aortic aneurysm	COL3A1	1	NA	
Orphanet:243	46,XX gonadal dysgenesis	NR5A1;MRPS22;FSHR;BMP15;PSMC3IP;NUP107;SPIDR	7	46,XX gonadal dysgenesis (46,XX GD) is a primary ovarian defect leading to premature ovarian failure (POF; see this term) in otherwise normal 46,XX females as a result of failure of the gonads to develop or due to resistance to gonadotrophin stimulation.	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Genetic infertility
Orphanet:136	CADASIL	NOTCH3	1	CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a hereditary cerebrovascular disorder characterized by mid-adult onset of recurrent subcortical ischemic stroke and cognitive impairment progressing to dementia in addition to migraines with aura and mood disturbances seen in about a third of patients.	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:48	Congenital bilateral absence of vas deferens	ADGRG2;CFTR	2	Congenital bilateral absence of the vas deferens (CBAVD) is a condition leading to male infertility.	Rare genetic urogenital disease;Genetic infertility
Orphanet:528	Berardinelli-Seip congenital lipodystrophy	CAVIN1;PPARG;BSCL2;AGPAT2;CAV1;FOS	6	Berardinelli-Seip congenital lipodystrophy (BSCL) is characterized by the association of lipoatrophy, hypertriglyceridemia, hepatomegaly and acromegaloid features. BSCL belongs to the group of extreme insulin resistance syndromes, which also includes leprechaunism, Rabson-Mendenhall syndrome, acquired generalized lipodystrophy, and types A and B insulin resistance (see these terms).	Rare genetic skin disease;Rare genetic endocrine disease;Rare genetic developmental defect during embryogenesis
Orphanet:275	Severe combined immunodeficiency due to DCLRE1C deficiency	DCLRE1C	1	Severe combined immunodeficiency (SCID) due to DCLRE1C deficiency is a type of SCID (see this term) characterized by severe and recurrent infections, diarrhea, failure to thrive, and cell sensitivity to ionizing radiation.	Rare genetic immune disease
Orphanet:184	Cherubism	SH3BP2	1	Cherubism is a rare, self-limiting, fibro-osseous, genetic disease of childhood and adolescence characterized by varying degrees of progressive bilateral enlargement of the mandible and/or maxilla, with clinical repercussions in severe cases.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic immune disease
Orphanet:71	Chylomicron retention disease	SAR1B	1	Chylomicron retention disease (CRD) is a type of familial hypocholesterolemia characterized by malnutrition, failure to thrive, growth failure, vitamin E deficiency and hepatic, neurologic and ophthalmologic complications.	Rare inborn errors of metabolism;Rare genetic endocrine disease;Rare genetic gastroenterological disease
Orphanet:1949	Benign familial neonatal epilepsy	KCNQ2;KCNQ3	2	Benign familial neonatal epilepsy (BFNE) is a rare genetic epilepsy syndrome characterized by the occurrence of afebrile seizures in otherwise healthy newborns with onset in the first few days of life.	Rare genetic neurological disorder
Orphanet:189	Hidrotic ectodermal dysplasia	GJB6	1	Clouston syndrome (or hidrotic ectodermal dysplasia) is characterised by the clinical triad of nail dystrophy, alopecia, and palmoplantar hyperkeratosis.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:1473	Uveal coloboma-cleft lip and palate-intellectual disability	YAP1	1	A rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by uveal coloboma (typically bilateral) variably associated with cleft lip, palate and/or uvula, hearing impairment, and intellectual disability. The spectrum of eye involvement is also variable and includes iris coloboma extending to the choroid, disc, and/or macula, microphthalmia, cataract, and extraocular movement impairment.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:1344	Atrial standstill	SCN5A;NPPA	2	A rare cardiac rhythm disease characterized by a transient or permanent absence of electrical and mechanical atrial activity. Electrocardiographic findings include bradycardia, ectopic supraventricular rhythms, lack of atrial excitability and absent P waves.	Rare genetic cardiac disease
Orphanet:182050	MYH9-related disease	MYH9	1	MYH9-related disease (MYH9-RD) is an inherited giant platelet disorder with a complex phenotype characterized by congenital thrombocytopenia and possible subsequent manifestations of sensorineural hearing loss, presenile cataracts, elevation of liver enzymes, and/or progressive nephropathy often leading to end-stage renal disease (ESRD). Epstein syndrome, Fechtner syndrome, May-Hegglin anomaly and Sebastian syndrome, previously described as distinct disorders, represent some of the different clinical presentations of MYH9-RD.	Genetic otorhinolaryngologic disease;Rare genetic renal disease;Rare genetic hematologic disease
Orphanet:3103	Roberts syndrome	ESCO2	1	Roberts syndrome (RBS) is characterized by pre- and postnatal growth retardation, severe symmetric limb reduction defects, craniofacial anomalies and severe intellectual deficit. SC phocomelia is a milder form of RBS.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease
Orphanet:709	Peters plus syndrome	B3GLCT	1	Peters plus syndrome is an autosomal recessively inherited syndromic developmental defect of the eye (see this term) characterized by a variable phenotype including Peters anomaly (see this term) and other anterior chamber eye anomalies, short limbs, limb abnormalities (i.e. rhizomelia and brachydactyly), characteristic facial features (upper lip with cupid bow, short palpebral fissures), cleft lip/palate, and mild to severe developmental delay/intellectual disability. Other associated abnormalities reported in some patients include congenital heart defects (i.e. hypoplastic left heart, absence of right pulmonary vein, bicuspid pulmonary valve), genitourinary anomalies (hydronephrosis, renal hypoplasia, renal and ureteral duplication, multicystic dysplastic kidneys, glomerulocystic kidneys) and congenital hypothyroidism.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic eye disease;Rare genetic neurological disorder;Rare genetic cardiac disease
Orphanet:776	X-linked intellectual disability with marfanoid habitus	MED12;ZDHHC9;UPF3B	3	The Lujan-Fryns syndrome or X-linked mental retardation (XLMR) with marfanoid habitus syndrome is a syndromic X-linked form of intellectual disability, associated with tall, marfanoid stature, distinct facial dysmorphism and behavioral problems.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:902	Werner syndrome	WRN	1	Werner syndrome (WS) is a rare inherited syndrome characterized by premature aging with onset in the third decade of life and with cardinal clinical features including bilateral cataracts, short stature, graying and thinning of scalp hair, characteristic skin disorders and premature onset of additional age-related disorders.	Inherited cancer-predisposing syndrome;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic skin disease
Orphanet:888	Van der Woude syndrome	IRF6;GRHL3	2	Van der Woude syndrome (VWS) is a rare congenital genetic dysmorphic syndrome characterized by paramedian lower-lip fistulae, cleft lip with or without cleft palate, or isolated cleft palate.	Rare genetic developmental defect during embryogenesis
Orphanet:871	Familial progressive cardiac conduction defect	SCN1B;SCN5A;NKX2-5;TRPM4	4	A genetic cardiac rhythm disease that may progress to complete atrioventricular (AV) block. The disease is either asymptomatic or manifests as dyspnea, dizziness, syncope, abdominal pain, heart failure or sudden death.	Rare genetic cardiac disease
Orphanet:1587	Monosomy 13q14	RB1	1	Monosomy 13q14 is a rare chromosomal anomaly syndrome, resulting from a partial deletion of the long arm of chromosome 13, characterized by developmental delay, variable degrees of intellectual disability, retinoblastoma and craniofacial dysmorphism (incl. micro/dolichocephaly, high and broad forehead, prominent eyebrows, thick, anteverted ear lobes, short nose with a broad nasal bridge and bulbous tip, prominent philtrum, large mouth with thin upper lip and thick, everted lower lip). Other features reported include high birth weight, macrocephaly, pinealoma, hepatomegaly, inguinal hernia and cryptorchidism.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare chromosomal anomaly
Orphanet:1627	Deletion 5q35	NKX2-5;NSD1	2	 (5q35.1). Various combinations of signs may result from deletions of variable extent depending on the genes comprised in the deleted segment.	Rare chromosomal anomaly
Orphanet:500	Noonan syndrome with multiple lentigines	PTPN11;BRAF;RAF1	3	A rare multisystem genetic disorder characterized by lentigines, hypertrophic cardiomyopathy, short stature, pectus deformity, and dysmorphic facial features.	Genetic otorhinolaryngologic disease;Rare genetic developmental defect during embryogenesis;Inherited cancer-predisposing syndrome;Rare genetic cardiac disease;Rare genetic skin disease;RASopathy
Orphanet:233	Duane retraction syndrome	COL25A1;CHN1;MAFB	3	A congenital form of strabismus characterized by horizontal eye movement limitation, globe retraction and palpebral fissure narrowing in attempted adduction. It is caused by a failure of development of the abducens nerve and can lead to amblyopia.	Rare genetic eye disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:569	Familial or sporadic hemiplegic migraine	SCN1A;CACNA1A;ATP1A2;PRRT2	4	A rare variety of migraine with aura characterized by the presence of a motor weakness during the aura. There are two main forms depending on the familial history: patients with at least one first- or second-degree relative who has aura including motor weakness have familial hemiplegic migraine (FHM); patients without such familial history have sporadic hemiplegic migraine (SHM).	Rare genetic neurological disorder
Orphanet:240	Léri-Weill dyschondrosteosis	SHOX	1	A rare skeletal dysplasia marked by disproportionate short stature and the characteristic Madelung wrist deformity.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2311	Autosomal recessive spondylocostal dysostosis	DLL3;MESP2;LFNG;HES7;RIPPLY2	5	A rare condition of variable severity associated with vertebral and rib segmentation defects and characterised by a short neck with limited mobility, winged scapulae, a short trunk, and short stature with multiple vertebral anomalies at all levels of the spine.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare inborn errors of metabolism
Orphanet:358	Gitelman syndrome	SLC12A3;CLCNKB	2	A rare syndrome characterized by hypokalemic metabolic alkalosis in combination with significant hypomagnesemia and low urinary calcium excretion.	Rare genetic renal disease
Orphanet:242	46,XY complete gonadal dysgenesis	WT1;SOX9;SRY;DHH;NR0B1;NR5A1;DMRT1;CBX2;MAP3K1	9	A rare disorder of sex development (DSD) associated with anomalies in gonadal development that result in the presence of female external and internal genitalia despite the 46,XY karyotype.	Rare genetic cardiac disease;Rare genetic skin disease;Rare genetic gynecological and obstetrical diseases;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease
Orphanet:2052	Fraser syndrome	FRAS1;FREM2;GRIP1	3	A rare clinical entity including as main characteristics cryptophthalmos and syndactyly.	Genetic otorhinolaryngologic disease;Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:1358	Carey-Fineman-Ziter syndrome	MYMK	1	Carey-Fineman-Ziter (CFZ) syndrome is a rare condition characterized by the association of hypotonia, Moebius sequence (bilateral congenital facial palsy with impairment of ocular abduction), Pierre-Robin sequence (micrognathia, glossoptosis, and high-arched or cleft palate), unusual face, and growth delay.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:111	Barth syndrome	TAZ	1	Barth syndrome (BTHS) is an inborn error of phospholipid metabolism characterized by dilated cardiomyopathy (DCM), skeletal myopathy, neutropenia, growth delay and organic aciduria.	Rare genetic cardiac disease;Rare genetic immune disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:1308	C syndrome	CD96	1	C syndrome is a rare multiple congenital anomaly/intellectual disability syndrome characterized by trigonocephaly and metopic suture synostosis, dysmorphic facial features, short neck, skeletal anomalies, and variable intellectual disability.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:150	Nasopharyngeal carcinoma	NFKBIA	1	Nasopharyngeal carcinoma (NPC) is a tumor arising from the epithelial cells that cover the surface and line the nasopharynx.	
Orphanet:133	Chronic beryllium disease	HLA-DPB1	1	Chronic beryllium disease (CBD) is a granulomatous, interstitial lung disease that occurs in individuals who develop beryllium sensitization (BeS), a cell-mediated immune response to environmental and occupational beryllium exposure. BeS precedes the lung disease that may present with chronic dry cough, fatigue, weight loss, chest pain, and increasing dyspnea.	
Orphanet:1552	Currarino syndrome	MNX1	1	Currarino syndrome (CS) is a rare congenital disease characterized by the triad of anorectal malformations (ARMs) (usually anal stenosis), presacral mass (commonly anterior sacral meningocele (ASM) or teratoma) and sacral anomalies (i.e. total or partial agenesis of the sacrum and coccyx or deformity of the sacral vertebrae).	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2615	Nakajo-Nishimura syndrome	PSMB8	1	Nakajo-Nishimura syndrome (NNS) is a rare autoinflammatory disorder belonging to the proteasome disability syndrome (see this term) group, and characterized by pernio-like lesions appearing in infancy followed by recurrent fever, nodular skin eruption, partial lipodystrophy (mainly in upper extremities and face) and joint contractures.	Rare genetic skin disease;Rare genetic endocrine disease;Rare genetic systemic or rheumatologic disease
Orphanet:624	Familial multiple nevi flammei	GNAQ	1	Familial multiple nevi flammei is a rare, genetic capillary malformation disorder characterized by dark red to purple birthmarks which manifest as flat, sharply circumscribed cutaneous lesions, typically situated in the head and neck region, in various members of a single family. The lesions grow proportionally with the individual, change in color and often thicken with age.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:3000	Familial male-limited precocious puberty	LHCGR	1	Familial male limited precocious puberty (FMPP) is a gonadotropin-independent familial form of male-limited precocious puberty, generally presenting between 2-5 years of age as accelerated growth, early development of secondary sexual characteristics and reduced adult height.	Rare genetic endocrine disease
Orphanet:920	Ablepharon macrostomia syndrome	TWIST2	1	An extremely rare multiple congenital malformation syndrome characterized by the association of ablepharon, macrostomia, abnormal external ears, syndactyly of the hands and feet, skin findings (such as dry and coarse skin or redundant folds of skin), absent or sparse hair, genital malformations and developmental delay (in 2/3 of cases). Other reported manifestations include malar hypoplasia, absent or hypoplastic nipples, umbilical abnormalities and growth retardation. It is a mainly sporadic disorder, although a few familial cases having been reported, and it displays significant clinical overlap with Fraser syndrome.	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:7	3C syndrome	WASHC5;CCDC22	2	Cranio-cerebello-cardiac (3C) syndrome is a rare multiple congenital anomalies syndrome characterized by craniofacial (prominent occiput and forehead, hypertelorism, ocular coloboma, cleft palate), cerebellar (Dandy-Walker malformation, cerebellar vermis hypoplasia) and cardiac (tetralogy of Fallot, atrial and ventricular septal defects) anomalies (see these terms).	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:931	Acheiropodia	LMBR1	1	An extremely rare developmental disorder characterized by bilateral, congenital and complete amputation of the distal extremities (amputation of distal epiphysis of the humerus, distal portion of the tibial diaphysis, aplasia of the radius, ulna, fibula) and aplasia of hands and feet (aplasia of carpal, metacarpal, tarsal, metatarsal and phalangeal bones). Rarely, an ectopic bone can be found at the distal end of the humerus. No other systemic manifestations have been reported and the disorder follows an autosomal recessive pattern of inheritance.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:869	Triple A syndrome	TRAPPC11;AAAS;GMPPA	3	Triple A syndrome is a very rare multisystem disease characterized by adrenal insufficiency with isolated glucocorticoid deficiency, achalasia, alacrima, autonomic dysfunction and neurodegeneration.	Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic endocrine disease;Rare genetic developmental defect during embryogenesis
Orphanet:2297	Insulin-resistance syndrome type A	INSR	1	Type A insulin-resistance syndrome belongs to the group of extreme insulin-resistance syndromes (which includes leprechaunism, the lipodystrophies, Rabson-Mendenhall syndrome and type B insulin resistance syndrome; see these terms) and is characterized by the triad of hyperinsulinemia, acanthosis nigricans (skin lesions associated with insulin resistance), and signs of hyperandrogenism in females without lipodystrophy and who are not overweight.	Genetic infertility;Rare genetic endocrine disease
Orphanet:921	Abruzzo-Erickson syndrome	TBX22	1	An orofacial clefting syndrome that is characterized by a cleft palate, ocular coloboma, hypospadias, mixed conductive-sensorineural hearing loss, short stature, and radio-ulnar synostosis.	Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease
Orphanet:31	Oxoglutaric aciduria	OGDH	1	A rare, genetic, inborn error of metabolism disorder characterized by neonatal-onset of developmental delay, hypotonia, hepatomegaly, lactic acidemia, increased creatine kinase levels, elevated alpha-ketoglutaric acid in urine, and a decreased plasma beta-hydroxybutyrate-to-acetoacetate ratio. Pyruvate dehydrogenase deficiency can be associated, leading to hypoglycemia and neurologic anomalies, including seizures.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:37	Acrodermatitis enteropathica	SLC39A4	1	A rare inherited inborn error of metabolism resulting in a severe zinc deficiency and characterized by acral dermatitis, alopecia, diarrhea and growth failure.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare inborn errors of metabolism;Rare genetic gastroenterological disease
Orphanet:950	Acrodysostosis	PRKAR1A;PDE4D	2	An acromelic dysplasia that is characterized by severe brachydactyly, peripheral dysostosis with facial dysostosis, nasal hypoplasia, and developmental delay.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:955	Acroosteolysis dominant type	NOTCH2	1	A rare genetic osteolysis syndrome characterized by acroosteolysis of distal phalanges and generalized osteoporosis, associated with additional ossification anomalies, craniofacial dysmorphism, dental anomalies and a wide range of other characteristics.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:952	Acrofacial dysostosis, Weyers type	EVC;EVC2	2	A rare ectodermal dysplasia syndrome with bone abnormalities characterized by onychodystrophy; anomalies of the lower jaw, oral vestibule and dentition; post-axialpolydactyly; moderately restricted growth with short limbs; and normal intelligence. Although it closely resembles Ellis-van Creveld syndrome (see this term), an allelic disorder and another type of ciliopathy, WAD is usually a milder disease without the presence of heart abnormalities and is inherited in an autosomal dominant manner.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic bone disease
Orphanet:1713	17p11.2 microduplication syndrome	RAI1	1	17p11.2 microduplication syndrome is a rare chromosomal anomaly syndrome, resulting from the partial duplication of the short arm of chromosome 17, typically characterized by hypotonia, poor feeding, failure to thrive, developmental delay (particularly cognitive and language deficits), mild-moderate intellectual deficit, and neuropsychiatric disorders (behavioral problems, anxiety, attention deficit hyperactivity disorder, autistic spectrum disorder, bipolar disorder). Structural cardiovascular anomalies (dilated aortic root, bicommissural aortic valve, atrial/ventricular and septal defects) and sleep disturbance (obstructive and central sleep apnea) are also frequently associated.	Rare genetic neurological disorder;Rare chromosomal anomaly
Orphanet:1762	Trisomy Xq28	MECP2	1	Distal Xq duplications refer to chromosomal disorders resulting from involvement of the long arm of the X chromosome (Xq). Clinical manifestations vary widely depending on the gender of the patient and on the gene content of the duplicated segment. The prevalence of Xq duplications remains unknown.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare chromosomal anomaly
Orphanet:1878	Autosomal recessive limb-girdle muscular dystrophy type 2H	TRIM32	1	A mild subtype of autosomal recessive limb girdle muscular dystrophy characterized by slowly progressive proximal muscle weakness and wasting of the pelvic and shoulder girdles with onset that usually occurs during the second or third decade of life. Clinical presentation is variable and can include calf psuedohypertrophy, joint contractures, scapular winging, muscle cramping and/or facial and respiratory muscle involvement.	Rare genetic neurological disorder
Orphanet:1946	Amelocerebrohypohidrotic syndrome	SLC13A5;ROGDI	2	Kohlschütter-Tönz syndrome (KTS) is a genetically heterogeneous autosomal recessive syndrome characterized by the triad of amelogenesis imperfect, infantile onset epilepsy, intellectual disability with or without regression and dementia.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:2604	Familial visceral myopathy	ACTG2	1	Familial visceral myopathy is a rare hereditary myopathic degeneration of both gastrointestinal and urinary tracts that causes chronic intestinal pseudo-obstruction. It usually presents after the first decade of life with megaduodenum, megacystis and symptoms such as abdominal distension and/or pain, vomiting, constipation, diarrhea, dysphagia, and/or urinary tract infections.n.	Rare genetic gastroenterological disease
Orphanet:156	Carnitine palmitoyl transferase 1A deficiency	CPT1A	1	Carnitine palmitoyltransferase 1A (CPT-1A) deficiency is an inborn error of metabolism that affects mitochondrial oxidation of long chain fatty acids (LCFA) in the liver and kidneys, and is characterized by recurrent attacks of fasting-induced hypoketotic hypoglycemia and risk of liver failure.	Rare inborn errors of metabolism
Orphanet:2598	Mitochondrial myopathy and sideroblastic anemia	PUS1;YARS2	2	Mitochondrial myopathy and sideroblastic anemia belongs to the heterogeneous family of metabolic myopathies. It is characterised by progressive exercise intolerance manifesting in childhood, onset of sideroblastic anaemia around adolescence, lactic acidaemia, and mitochondrial myopathy.	Rare genetic neurological disorder;Rare genetic hematologic disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:1071	Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome	TP63	1	An ectodermal dysplasia syndrome with defining features of ankyloblepharon filiforme adnatum (AFA), ectodermal abnormalities and a cleft lip and/or palate.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic bone disease;Rare genetic eye disease
Orphanet:1053	Vein of Galen aneurysmal malformation	EPHB4	1	A congenital vascular malformation characterized by dilation of the embryonic precursor of the vein of Galen. It is a sporadic lesion that occurs during embryogenesis.	
Orphanet:1052	Mosaic variegated aneuploidy syndrome	TRIP13;BUB1B;CEP57;BUB1;BUB3	5	Mosaic variegated aneuploidy (MVA) syndrome is a chromosomal anomaly characterized by multiple mosaic aneuploidies that leads to a variety of phenotypic abnormalities and cancer predisposition.	Inherited cancer-predisposing syndrome;Rare genetic eye disease
Orphanet:1040	Metaphyseal anadysplasia	MMP13;MMP13;MMP9	3	Metaphyseal anadysplasia is a very rare form of metaphyseal dysplasia characterized by short stature, rhizomelic micromelia and a mild varus deformity of the legs evident from the first months of life, that is associated with radiological features of severe metaphyseal changes (irregularities, widening and marginal blurring) in long bones, most prominent in proximal femurs, and generalized osteopenia, and that usually spontaneously resolves by the age of three years. Severe autosomal dominant and milder recessive variants have been observed.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:1106	Microphthalmia with limb anomalies	SMOC1	1	A rare developmental disorder characterized by bilateral microphthalmia or anophthalmia, synostosis, syndactyly, oligodactyly and/or polydactyly.	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:83	Antley-Bixler syndrome	FGFR2	1	A very rare disorder characterised by craniosynostosis with midface hypoplasia, radiohumeral synostosis, femoral bowing and joint contractures.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:990	Agnathia-holoprosencephaly-situs inversus syndrome	OTX2;PRRX1	2	An extremely rare and fatal association syndrome, characterized by absence of the mandible, cerebral malformations with facial anomalies related to a defect in cleavage in the embryonic brain (e.g. synophthalmia, malformed and low-set ears fused in midline (otocephaly), agenesis of the olfactory bulbs, microstomia, hypoglossia/aglossia) and situs inversus partialis or totalis.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:994	Fetal akinesia deformation sequence	MYOD1;RAPSN;DOK7;MUSK	4	The fetal akinesia/hypokinesia sequence (or Pena-Shokeir syndrome type I) is characterized by multiple joint contractures, facial anomalies and pulmonary hypoplasia. Whatever the cause, the common feature of this sequence is decreased foetal activity.	Rare genetic developmental defect during embryogenesis
Orphanet:51	Aicardi-Goutières syndrome	SAMHD1;RNASEH2A;RNASEH2B;RNASEH2C;ADAR;TREX1;IFIH1	7	An inherited, subacute encephalopathy characterised by the association of basal ganglia calcification, leukodystrophy and cerebrospinal fluid (CSF) lymphocytosis.	Rare genetic neurological disorder;Rare genetic systemic or rheumatologic disease;Rare genetic immune disease
Orphanet:978	ADULT syndrome	TP63	1	A rare ectodermal dysplasia syndrome characterized by ectrodactyly, syndactyly, mammary hypoplasia, and excessive freckling as well as other typical ectodermal defects such as hypodontia, lacrimal duct anomalies, hypotrichosis, and onychodysplasia.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease;Rare genetic skin disease
Orphanet:970	Hereditary sensory and autonomic neuropathy type 2	SCN9A;WNK1;RETREG1;KIF1A	4	A rare hereditary sensory and autonomic neuropathy characterized by profound and universal sensory loss involving large and small fiber nerves.	Rare genetic neurological disorder
Orphanet:40	Acromesomelic dysplasia, Maroteaux type	NPR2	1	120 cm), both axial and appendicular involvement (shortening of the middle and distal segments of limbs and vertebral shortening), and with normal facial appearance and intelligence. It is a less severe form than acromesomelic dysplasia, Grebe type and acromesomelic dysplasia, Hunter-Thomson type .	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:969	Acromicric dysplasia	FBN1;LTBP3	2	A rare bone dysplasia characterized by short stature, short hands and feet, mild facial dysmorphism, and characteristic X-ray abnormalities of the hands.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:974	Adams-Oliver syndrome	NOTCH1;ARHGAP31;DOCK6;RBPJ;EOGT;DLL4	6	A rare disorder characterized by the combination of congenital limb abnormalities and scalp defects, often accompanied by skull ossification defects.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic skin disease
Orphanet:972	Hereditary continuous muscle fiber activity	KCNA1	1	Hereditary continuous muscle fiber activity is a rare, non-dystrophic myopathy characterized by generalized myokymia and increased muscle tone associated with delayed motor milestones, leg stiffness, spastic gait, hyperreflexia and Babinski sign. Symptoms may be worsened by febrile illness or anesthesia.	Rare genetic neurological disorder
Orphanet:959	Acro-renal-ocular syndrome	SALL4	1	 related disorders including Okihiro syndrome and Holt-Oram syndrome.	Rare genetic developmental defect during embryogenesis
Orphanet:968	Acromesomelic dysplasia, Hunter-Thompson type	GDF5	1	A rare autosomal recessive acromesomelic dysplasia characterized by severe dwarfism (adult height approximately 120 cm) with abnormalities limited to the limbs (affecting the lower limbs more than upper limbs, with middle and distal segments being the most affected), severe shortening, absence or fusion of tubular bones of hands and feet and large joint dislocations. As seen in acromesomelic dysplasia, Grebe type and acromesomelic dysplasia, Maroteaux type, facial features and intelligence are normal.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:965	Acromegaloid facial appearance syndrome	ABCC9	1	A rare multiple congenital anomalies/dysmorphic syndrome with a probable autosomal dominant inheritance, characterized by a progressively coarse acromegaloid-like facial appearance with thickening of the lips and intraoral mucosa, large and doughy hands and, in some cases, developmental delay. AFA syndrome appears to be part of a phenotypic spectrum that includes hypertrichotic osteochondrodysplasia, Cantu type and hypertrichosis-acromegaloid facial appearance syndrome.	Rare genetic developmental defect during embryogenesis
Orphanet:966	Hypertrichosis-acromegaloid facial appearance syndrome	ABCC9	1	Hypertrichosis-acromegaloid facial appearance syndrome (HAFF) is a very rare multiple congenital abnormality syndrome manifesting from birth with progressive hypertrichosis congenita terminalis (thick scalp hair extending onto the forehead with generalized increased body hair) associated with a typical acromegaloid facial appearance (thick eyebrows, prominent supraorbital ridges, broad nasal bridge, anteverted nares, long and large philtrum, and prominent mouth with full lips) appearing during childhood. HAFF seems to belong to a spectrum of phenotypes with the clinically overlapping acromegaloid facial appearance syndrome and hypertrichotic osteochondrodysplasia, Cantù type (see these terms).	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:1031	Enamel-renal syndrome	FAM20A	1	A extremely rare, genetic malformation syndrome characterized by hypoplastic amelogenesis imperfecta (hypoplastic dental enamel) and nephrocalcinosis (precipitation of calcium salts in renal tissue). Oral manifestations include yellow and misshaped teeth, delayed tooth eruption, and intrapulpal calcifications. Nephrocalcinosis is often asymptomatic but can progress during late childhood or early adulthood to impaired renal function, recurrent urinary infections, renal tubular acidosis, and rarely to end-stage renal failure.	Rare genetic developmental defect during embryogenesis;Rare genetic renal disease
Orphanet:64	Alström syndrome	ALMS1	1	A rare multisystemic disorder characterized by cone-rod dystrophy, hearing loss, obesity, insulin resistance and hyperinsulinemia, type 2 diabetes mellitus, dilated cardiomyopathy (DCM), and progressive hepatic and renal dysfunction.	Genetic otorhinolaryngologic disease;Rare genetic renal disease;Ciliopathy;Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease;Rare genetic eye disease;Rare genetic cardiac disease
Orphanet:139396	X-linked cerebral adrenoleukodystrophy	ABCD1	1	A subtype of X-linked adrenoleukodystrophy (X-ALD), a peroxisomal disease characterized by severe inflammatory demyelination in the brain, and often associated with adrenal insufficiency.	Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic endocrine disease;Genetic infertility
Orphanet:139399	Adrenomyeloneuropathy	ABCD1	1	An adult form of the peroxisomal disease X-linked adrenoleukodystrophy (X-ALD), characterized by spastic paraparesia and often associated with peripheral adrenal insufficiency in males.	Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic endocrine disease;Genetic infertility
Orphanet:139406	Encephalopathy due to prosaposin deficiency	PSAP	1	A lysosomal storage disease belonging to the group of sphingolipidoses.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:701	Alopecia universalis	HR	1	A disorder of most severe form of alopecia areata, an inflammatory disease of the hair follicle, which is characterized by a complete loss of hair of the scalp and all the hair-bearing areas of the body.	Rare genetic skin disease
Orphanet:1010	Autosomal dominant palmoplantar keratoderma and congenital alopecia	GJA1	1	A rare genetic skin disorder characterized by absence of scalp and body hair and palmoplantar keratoderma, without other hand complications.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:1001	2q37 microdeletion syndrome	HDAC4	1	Deletion 2q37 or monosomy 2q37 is a chromosomal anomaly involving deletion of chromosome band 2q37 and manifests as three major clinical findings: developmental delay, skeletal malformations and facial dysmorphism.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare chromosomal anomaly
Orphanet:59	Allan-Herndon-Dudley syndrome	SLC16A2	1	An X-linked intellectual disability syndrome with neuromuscular involvement characterized by infantile hypotonia, muscular hypoplasia, spastic paraparesis with dystonic/athetoic movements, and severe cognitive deficiency.	Rare genetic neurological disorder;Rare genetic endocrine disease
Orphanet:127	Borjeson-Forssman-Lehmann syndrome	PHF6	1	Borjeson-Forssman-Lehmann syndrome (BFLS) is a rare X-linked obesity syndrome characterized by intellectual deficit, truncal obesity, characteristic facial features, hypogonadism, tapered fingers and short toes.	Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease;Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:1263	Boomerang dysplasia	FLNB	1	Boomerang dysplasia (BD) is a rare lethal skeletal dysplasia characterized by severe short-limbed dwarfism, dislocated joints, club feet, distinctive facies and diagnostic x-ray findings of underossified and dysplastic long tubular bones, with a boomerang-like bowing.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:1234	Bartsocas-Papas syndrome	RIPK4	1	Bartsocas-Papas syndrome is a rare, inherited, popliteal pterygium syndrome (see this term) characterized by severe popliteal webbing, microcephaly, a typical face with short palpebral fissures, ankyloblepharon, hypoplastic nose, filiform bands between the jaws and facial clefts, oligosyndactyly, genital abnormalities, and additional ectodermal anomalies (i.e. absent hair, eyebrows, lashes, nails). It is often fatal in the neonatal period, but patients living until childhood have been reported.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:1231	Barber-Say syndrome	TWIST2	1	Barber Say syndrome (BSS) is a rare ectodermal dysplasia with neonatal onset characterized by congenital generalized hypertrichosis, atrophic skin, ectropion and microstomia.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic eye disease
Orphanet:1229	Congenital intrauterine infection-like syndrome	OCLN	1	Congenital intrauterine infection-like syndrome is characterised by the presence of microcephaly and intracranial calcifications at birth accompanied by neurological delay, seizures and a clinical course similar to that seen in patients after intrauterine infection with Toxoplasma gondii, Rubella, Cytomegalovirus, Herpes simplex (so-called TORCH syndrome), or other agents, despite repeated tests revealing the absence of any known infectious agent.	
Orphanet:109	Bannayan-Riley-Ruvalcaba syndrome	PTEN	1	Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a rare congenital disorder characterized by hamartomatous intestinal polyposis, lipomas, macrocephaly and genital lentiginosis.	Rare genetic neurological disorder;Rare genetic gastroenterological disease;Rare genetic developmental defect during embryogenesis;Inherited cancer-predisposing syndrome
Orphanet:115	Congenital contractural arachnodactyly	FBN2	1	Congenital contractural arachnodactyly (CCA, Beals syndrome) is a connective tissue disorder characterized by multiple flexion contractures, arachnodactyly, severe kyphoscoliosis, abnormal pinnae and muscular hypoplasia.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic systemic or rheumatologic disease
Orphanet:137625	Glycogen storage disease due to muscle and heart glycogen synthase deficiency	GYS1	1	Glycogen storage disease due to muscle and heart glycogen synthase deficiency is characterised by muscle and heart glycogen deficiency. It has been described in three siblings (two brothers and their younger sister). The older brother died at 10.5 years of age as a result of sudden cardiac arrest and the younger brother presented with hypertrophic cardiomyopathy, abnormal heart rate and blood pressure during exercise, and muscle fatigability. The sister showed no symptoms but a lack of glycogen was identified through muscle biopsy. The syndrome is caused by homozygous missense mutations in the gene encoding muscle glycogen synthase.	Rare inborn errors of metabolism;Rare genetic cardiac disease
Orphanet:137608	Segmental outgrowth-lipomatosis-arteriovenous malformation-epidermal nevus syndrome	PTEN	1	Segmental outgrowth-lipomatosis-arteriovenous malformation-epidermal nevus syndrome is a rare, genetic, polymalformative syndrome characterized by progressive, proportionate, asymmetric segmental overgrowth (with soft tissue hypertrophy and ballooning effect) that develops and progresses rapidly in early childhood, arteriovenous and lymphatic vascular malformations, lipomatosis and linear epidermal nevus (arranged in whorls along the lines of Blaschko). Clinical symptoms of Cowden syndrome, such as macrocephaly and progressive development of numerous hypertrophic hamartomatous and neoplastic lesions involving multiple organs and systems, are also associated. Patients present an increased risk of developing cancer.	Rare genetic tumor;Rare genetic developmental defect during embryogenesis;Inherited cancer-predisposing syndrome
Orphanet:1299	Branchioskeletogenital syndrome	CDH11	1	Branchioskeletogenital syndrome is a rare multiple congenital anomalies/dysmorphic syndrome characterized by moderate intellectual disability, distinctive craniofacial features (including brachycephaly, facial asymmetry, marked hypertelorism, blepharochalasis, proptosis, a broad nose with concave nasal ridge and bulbous nasal tip, midface hypoplasia, bifid uvula or partial cleft palate, and prognathism), progressive dental anomalies (dentigerous cysts, radicular dentin dysplasia and early tooth loss), vertebral fusions (particularly of C2-C3), and hypospadias. Hearing loss is an additional observed feature.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease
Orphanet:1300	Autosomal dominant popliteal pterygium syndrome	IRF6	1	A rare genetic, multiple congenital anomalies syndrome characterized by cleft lip, with or without cleft palate, pits in the lower lip, contractures of the lower extremities, abnormal external genitalia, syndactyly of fingers and/or toes, and a pyramidal skin fold over the hallux nail.	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:137667	Capillary malformation-arteriovenous malformation	RASA1	1	This syndrome is characterised by the association of multiple capillary malformations (CM) with an arteriovenous malformation (AVM) and arteriovenous fistulas.	Rare genetic developmental defect during embryogenesis
Orphanet:137634	Overgrowth-macrocephaly-facial dysmorphism syndrome	RNF135	1	This syndrome is characterised by tall stature, learning difficulties and facial dysmorphism.	Rare genetic developmental defect during embryogenesis
Orphanet:1297	Branchio-oculo-facial syndrome	TFAP2A	1	Branchio-oculo-facial syndrome (BOFS) is characterised by low birth weight and growth retardation, bilateral branchial clefts that may be hemangiomatous, sometimes with linear skin lesions behind the ears ('burn-like' lesions), congenital strabismus, obstructed nasolacrimal ducts, a broad nasal bridge with a flattened nasal tip, a protruding upper lip with an unusually broad and prominent philtrum, and full mouth.	Rare genetic developmental defect during embryogenesis
Orphanet:137639	Hypomyelinating leukodystrophy-ataxia-hypodontia-hypomyelination syndrome	POLR3A	1	Hypomyelinating leukodystrophy-ataxia-hypodontia-hypomyelination syndrome is a rare, genetic, neurological disorder characterized by early-onset, progressive ataxia, white matter hypomyelination and cerebellar atrophy on brain MRI imaging, and various dental abnormalities, including hypodontia, delayed primary tooth eruption, complete retention of the primary maxillary central incisors and abnormal shape of the permanent maxillary incisors.	Rare genetic neurological disorder
Orphanet:1276	Brachydactyly-arterial hypertension syndrome	PDE3A	1	Brachydactyly - arterial hypertension is a rare genetic brachydactyly syndrome characterized by the association of brachydactyly type E (see this term) with hypertension (due to vascular or neurovascular anomalies) as well as the additional features of short stature and low birth weight (compared to non-affected family members), stocky build and a round face. The onset of hypertension is often in childhood and, if untreated, most patients will have had a stroke by the age of 50.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic renal disease
Orphanet:1275	Brachydactyly-elbow wrist dysplasia syndrome	PITX1	1	Brachydactyly-elbow wrist dysplasia syndrome is a rare, genetic bone development disorder characterized by dysplasia of all the bony components of the elbow joint, abnormally shaped carpal bones, wrist joint radial deviation and brachydactyly. Patients typically present with slight flexion at the elbow joints (with impossibilty to perform active extension) and usually associate a limited range of motion of the elbow, wrist and finger articulations. Camptodactyly and syndactyly have also been reported.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:1270	Bowen-Conradi syndrome	EMG1	1	Bowen-Conradi syndrome (BCS) is a lethal autosomal recessive ribosomal biogenesis disorder characterized by severe prenatal and postnatal growth retardation, macrocephaly, a distinctive facial appearance, extreme psychomotor delay, hip and knee contractures and rockerbottom feet.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:137605	Legius syndrome	SPRED1	1	Legius syndrome, also known as NF1-like syndrome, is a rare, genetic skin pigmentation disorder characterized by multiple café-au-lait macules with or without axillary or inguinal freckling.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:1168	Ataxia-oculomotor apraxia type 1	APTX	1	A rare autosomal recessive cerebellar ataxia, characterized by progressive cerebellar ataxia associated with oculomotor apraxia, severe neuropathy, and hypoalbuminemia.	Rare genetic eye disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:137834	Frank-Ter Haar syndrome	SH3PXD2B	1	A rare primary bone dysplasia characterized by megalocornea, multiple skeletal anomalies, characteristic facial dysmorphism (wide fontanels, prominent forehead, hypertelorism, prominent eyes, full cheeks and micrognathia) and developmental delay.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:137831	X-linked intellectual disability-cerebellar hypoplasia syndrome	OPHN1	1	X-linked intellectual deficit-cerebellar hypoplasia, also known as OPHN1 syndrome, is a rare syndromic form of cerebellar dysgenesis characterized by moderate to severe intellectual deficit and cerebellar abnormalities.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:1170	Autosomal recessive cerebelloparenchymal disorder type 3	PMPCA	1	The disorders involving primarily the cerebellar parenchyma have been classified into six forms. In cerebelloparenchymal disorder III, cerebellar ataxia is congenital (non-progressive) and characterized by cerebellar symptoms such as incoordination of gait often associated with poor coordination of hands, speech and eye movements. The other features are congenital mental retardation and hypotonia, in addition to other neurological and non-neurological features. MRI or CT scan show marked atrophy of the vermis and hemispheres. A severe loss of granule cells with heterotopic Purkinje cells is observed. The mode of inheritance in the few reported families is autosomal recessive. In one family, cerebellar ataxia was associated to albinism.: In a large inbred Lebanese family the disease locus was assigned to a 12.1-cM interval on chromosome 9q34-qter between markers D9S67 and D9S312. The primary biochemical defect remains unknown. Up to now, the only treatment has consisted in early interventional therapies including intensive speech therapy and adequate stimulation and/or training.	Rare genetic eye disease;Rare genetic neurological disorder
Orphanet:1175	X-linked progressive cerebellar ataxia	GJB1	1	A rare X-linked cerebellar ataxia, characterized by a combination of upper and lower motor neuron signs, with an age of onset in the first or second decade, slow progression, and normal intelligence. Typical features of cerebellar dysfunction include gait and limb ataxia, intention tremor, dysmetria, dysdiadochokinesia, dysarthria, nystagmus, and hyperreflexia. Further phenotypic features are pes cavus, scoliosis, muscle atrophy, and peripheral sensory and motor nerve abnormalities.	Rare genetic neurological disorder
Orphanet:1180	Ataxia-hypogonadism-choroidal dystrophy syndrome	PNPLA6	1	A very rare autosomal recessive, slowly progressive neurodegenerative disorder characterized by the triad of cerebellar ataxia (that generally manifests at adolescence or early adulthood), chorioretinal dystrophy, which may have a later onset (up to the fifth-sixth decade) leading to variable degrees of visual impairment, and hypogonadotropic hypogonadism (delayed puberty and lack of secondary sex characteristics). Ataxia-hypogonadism-choroidal dystrophy syndrome belongs to a clinical continuum of neurodegenerative disorders along with the clinically overlapping cerebellar ataxia-hypogonadism syndrome (see this term).	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility;Rare genetic eye disease;Rare genetic neurological disorder
Orphanet:1173	Cerebellar ataxia-hypogonadism syndrome	PNPLA6;RNF216	2	Cerebellar ataxia-hypogonadism syndrome is a very rare autosomal recessive neurodegenerative disorder characterized by the combination of progressive cerebellar ataxia with onset from early childhood to the fourth decade, and hypogonadotropic hypogonadism (delayed puberty and lack of secondary sex characteristics). Cerebellar ataxia-hypogonadism syndrome belongs to a clinical continuum of neurodegenerative disorders along with clinically overlapping disorders such as ataxia-hypogonadism-choroidal dystrophy syndrome (see this term).	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility;Rare genetic neurological disorder
Orphanet:137681	Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1	GFM1	1	Hepatoencephalopathy due to combined oxidative phosphorylation deficiency type 1 is a rare, inherited mitochondrial disorder due to a defect in mitochondrial protein synthesis characterized by intrauterine growth retardation, metabolic decompensation with recurrent vomiting, persistent severe lactic acidosis, encephalopathy, seizures, failure to thrive, severe global developmental delay, poor eye contact, severe muscular hypotonia or axial hypotonia with limb hypertonia, hepatomegaly and/or liver dysfunction and/or liver failure, leading to fatal outcome in severe cases. Neuroimaging abnormalities may include corpus callosum thinning, leukodystrophy, delayed myelination and basal ganglia involvement.	Rare genetic hepatic disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:137675	Histiocytoid cardiomyopathy	MT-CYB	1	Histiocytoid cardiomyopathy is an arrhythmogenic disorder characterised by cardiomegaly, severe cardiac arrhythmias or sudden death, and the presence of histiocyte-like cells within the myocardium.	Rare genetic cardiac disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:137678	Czech dysplasia, metatarsal type	COL2A1	1	Czech dysplasia, metatarsal type is a form of skeletal dysplasia characterised by severe arthropathy beginning in childhood and hypoplasia/dysplasia of the third, fourth and/or fifth toes.	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:1145	Infantile-onset X-linked spinal muscular atrophy	UBA1	1	 and followed by bone fractures shortly after birth. SMAX2 patients often have a limited life span, often succumbing to the disease within 2 years, as muscle weakness is progressive and chest muscle involvement eventually leads to ventilatory insufficiency and respiratory failure.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:137754	Neurological conditions associated with aminoacylase 1 deficiency	ACY1	1	An inborn error of metabolism marked by a characteristic pattern of urinary N-acetyl amino acid excretion and neurologic symptoms.	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:137776	Lethal congenital contracture syndrome type 2	ERBB3	1	Lethal congenital contracture syndrome type 2 is a rare arthrogryposis syndrome characterized by multiple congenital contactures (typically extended elbows and flexed knees), micrognathia, anterior horn cell degeneration, skeletal muscle atrophy (mainly in the lower limbs), presence of a markedly distended urinary bladder and absence of hydrops, pterygia and bone fractures. Other craniofacial (e.g. cleft palate, facial palsy) and ocular (e.g. anisocoria, retinal detachment) anomalies may be additionally observed. The disease is usually neonatally lethal however, survival into adolescence has been reported.	Rare genetic developmental defect during embryogenesis
Orphanet:1149	Kuskokwim syndrome	FKBP10	1	A very rare congenital contracture disorder, reported exclusively in Yup'ik Eskimos of the Kuskokwim River delta region of Alaska, characterized by multiple contractures of large joints (predominantly the knees and ankles) that present at birth or during childhood but are lifelong; deformities of the spine, pelvis and feet; and sometimes proximally or distally displaced patellae and muscle atrophy in the limbs with contractures. Additional radiological features include mild vertebral wedging, elongation of the vertebral pedicle, and clubbing of the distal clavicle. An autosomal recessive pattern of inheritance has been suggested.	Rare genetic developmental defect during embryogenesis
Orphanet:1159	Progressive pseudorheumatoid arthropathy of childhood	WISP3	1	Progressive pseudorheumatoid arthropathy (dysplasia) of childhood (PPAC; PPD) presents as spondyloepiphyseal dysplasia (SED) tarda with progressive arthropathy and is described as a specific autosomal recessive subtype of SED.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:137783	Lethal congenital contracture syndrome type 3	PIP5K1C;MYBPC1	2	Lethal congenital contracture syndrome type 3 is a rare arthrogryposis syndrome characterized by clinical features identical to Lethal congenital contracture syndrome type 2 (i.e. multiple congenital contactures (typically extended elbows and flexed knees), micrognathia, anterior horn cells degeneration, skeletal muscle atrophy (mainly in the lower limbs), in the absence of hydrops, pterygia or bone fractures), but without bladder enlargement.	Rare genetic developmental defect during embryogenesis
Orphanet:1215	Autosomal dominant optic atrophy plus syndrome	OPA1	1	A rare variant of autosomal dominant optic atrophy (ADOA) associating the typical optic atrophy with other extra-ocular manifestations such as sensorineural deafness, myopathy, chronic progressive external ophthalmoplegia, ataxia and peripheral neuropathy. More rarely, other manifestations have been associated with this condition, such as spastic paraplegia, multiple-sclerosis like illness.	Rare genetic eye disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:1216	Autosomal dominant congenital benign spinal muscular atrophy	TRPV4	1	A rare distal hereditary motor neuropathy, with a variable clinical phenotype, typically characterized by congenital, non-progressive, predominantly distal, lower limb muscle weakness and atrophy and congenital (or early-onset) flexion contractures of the hip, knee and ankle joints. Reduced or absent lower limb deep tendon reflexes, skeletal anomalies (bilateral talipes equinovarus, scoliosis, kyphoscoliosis, lumbar hyperlordisis), late ambulation, waddling gait, joint hyperlaxity and/or bladder and bowel dysfuntion are usually also associated.	Rare genetic neurological disorder
Orphanet:1225	Baller-Gerold syndrome	RECQL4	1	Baller-Gerold syndrome is characterized by the association of coronal craniosynostosis with radial ray anomalies (oligodactyly, aplasia or hypoplasia of the thumb, aplasia or hypoplasia of the radius).	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:1226	Bamforth-Lazarus syndrome	FOXE1	1	A very rare syndrome of congenital hypothyroidism characterized by thyroid dysgenesis (in most cases athyreosis), cleft palate and spiky hair, with or without choanal atresia, and bifid epiglottis. Facial dysmorphism and porencephaly have been reported in isolated cases.	Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease
Orphanet:137888	Auriculocondylar syndrome	GNAI3;PLCB4;EDN1	3	A rare disorder that presents with bilateral external ear malformations ('question mark' ears), mandibular condyle hypoplasia, microstomia, micrognathia, microglossia and facial asymmetry. Additional manifestations include hypotonia, ptosis, cleft palate, puffy cheeks, developmental delay, impaired hearing and respiratory distress.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:137893	Male infertility due to large-headed multiflagellar polyploid spermatozoa	AURKC	1	Male infertility due to large-headed multiflagellar polypoid spermatozoa is a male infertility due to sperm disorder characterized by the presence, in sperm, of a very high percentage of spermatozoa with enlarged head, irregular head shape, multiple flagella, and abnormal midpiece and acrosome. It is generally associated with severe oligoasthenozoospermia and a high rate of sperm chromosomal abnormalities (polyploidy, aneuploidy).	Genetic infertility
Orphanet:1186	Infantile onset spinocerebellar ataxia	TWNK	1	Infantile-onset spinocerebellar ataxia (IOSCA) is a hereditary neurological disorder with early and severe involvement of both the peripheral and central nervous systems. It has only been described in Finnish families.	Rare genetic neurological disorder;Rare genetic hepatic disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic gastroenterological disease
Orphanet:137898	Leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome	DARS2	1	This disease is characterised by progressive cerebellar ataxia with pyramidal and spinal cord dysfunction, associated with distinctive MRI anomalies and increased lactate in the abnormal white matter.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:137902	Isolated optic nerve hypoplasia/aplasia	PAX6	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:1187	Lethal ataxia with deafness and optic atrophy	PRPS1	1	Lethal ataxia with deafness and optic atrophy (also known as Arts syndrome) is characterized by intellectual deficit, early-onset hypotonia, ataxia, delayed motor development, hearing impairment and loss of vision due to optic atrophy.	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:137908	Hypotonia with lactic acidemia and hyperammonemia	MRPS22	1	This syndrome is characterised by severe hypotonia, lactic academia and congenital hyperammonaemia.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:1190	Atelosteogenesis type I	FLNB	1	A Pierre Robin syndrome associated with bone disease characterized by severe short-limbed dwarfism, joint dislocations, club feet along with distinctive facies and radiographic findings.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:1200	Choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome	POLR1A;TXNL4A	2	Choanal atresia - deafness - cardiac defects - dysmorphism syndrome, also known as Burn-McKeown syndrome, is an extremely rare multiple congenital anomaly syndrome characterized by bilateral choanal atresia (see this term) associated with a characteristic cranio-facial dysmorphism (hypertelorism with narrow palpebral fissures, coloboma of inferior eyelid (see this term) with presence of eyelashes medial to the defect, prominent nasal bridge, thin lips, prominent ears), that can be accompanied by hearing loss, unilateral cleft lip, preauricular tags, cardiac septal defects and anomalies of the kidneys. The features of this syndrome overlaps considerably with those of the CHARGE syndrome (see this term).	Genetic otorhinolaryngologic disease;Rare genetic developmental defect during embryogenesis
Orphanet:141258	Tessier number 4 facial cleft	SPECC1L	1	NA	Rare genetic developmental defect during embryogenesis
Orphanet:1458	CODAS syndrome	LONP1	1	Codas syndrome is a multiple congenital anomalies syndrome characterized by Cerebral, Ocular, Dental, Auricular and Skeletal anomalies.	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic bone disease
Orphanet:1454	Joubert syndrome with hepatic defect	TMEM67;RPGRIP1L;CC2D2A;INPP5E	4	Joubert syndrome with hepatic defect is a very rare subtype of Joubert syndrome and related disorders (JSRD, see this term) characterized by the neurological features of JS associated with congenital hepatic fibrosis (CHF).	Rare genetic developmental defect during embryogenesis;Ciliopathy;Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic hepatic disease
Orphanet:190	Coats disease	NDP	1	Coats disease (CD) is an idiopathic disorder characterized by retinal telangiectasia with deposition of intraretinal or subretinal exudates, potentially leading to retinal detachment and unilateral blindness. CD is classically an isolated and unilateral condition affecting otherwise healthy young children.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:1429	Benign hereditary chorea	NKX2-1;ADCY5	2	A rare, genetic, movement disorder characterized by early-onset, very slowly progressive choreiform movements that may involve variable parts of the body, typically aggravated by stress or anxiety, in various members of a family. Additional variable manifestations include hypotonia, often resulting in psychomotor delay (including gait disturbances) and dysarthria, as well as myoclonus, dystonia, behavioral symptoms (ADHD, obsessive-compulsive disorder), learning difficulties (particularly in writing) and spasticity with hyperreflexia and/or flexor/extensor plantar reflexes.	Rare genetic neurological disorder
Orphanet:1426	Greenberg dysplasia	LBR	1	 lethality and affected fetuses are considered as nonviable.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare inborn errors of metabolism
Orphanet:1427	Otospondylomegaepiphyseal dysplasia	COL11A2	1	Otospondylomegaepiphyseal dysplasia (OSMED) is an inborn error of cartilage collagen formation characterized by sensorineural hearing loss, enlarged epiphyses, skeletal dysplasia with disproportionately short limbs, vertebral body anomalies and a characteristic facies.	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:1490	Corneal dystrophy-perceptive deafness syndrome	SLC4A11	1	Corneal dystrophy-perceptive deafness (CDPD) or Harboyan syndrome is a degenerative corneal disorder characterized by the association of congenital hereditary endothelial dystrophy (CHED; see this term) with progressive, postlingual sensorineural hearing loss.	Genetic otorhinolaryngologic disease;Rare genetic eye disease
Orphanet:155878	Submucosal cleft palate	GRHL3;UBB	2	NA	
Orphanet:1486	Lethal congenital contracture syndrome type 1	GLE1	1	Lethal congenital contracture syndrome type 1 is a rare, genetic arthrogryposis syndrome characterized by total fetal akinesia (detectable since the 13th week of gestation) accompanied by hydrops, micrognathia, pulmonary hypoplasia, pterygia and multiple joint contractures (usually flexion contractures in the elbows and extension in the knees), leading invariably to death before the 32nd week of gestation. Lack of anterior horn motoneurons, severe atrophy of the ventral spinal cord and severe skeletal muscle hypoplasia are characteristic neuropathological findings, with no evidence of other organ structural anomalies.	Rare genetic developmental defect during embryogenesis
Orphanet:141276	Tessier number 7 facial cleft	PTCH2;SPECC1L	2	NA	Rare genetic developmental defect during embryogenesis
Orphanet:1466	COFS syndrome	ERCC2;ERCC6;ERCC5;ERCC1	4	Cerebrooculofacioskeletal (COFS) syndrome is a rare genetic disorder, belonging to a family of diseases of DNA repair, characterized by a severe sensorineural involvement.	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder;Inherited cancer-predisposing syndrome;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic skin disease
Orphanet:141291	Cleft lip and alveolus	MSX1;TP63;IRF6;NECTIN1	4	Cleft lip and alveolus is a fissure type embryopathy that involves the upper lip, nasal base and alveolar ridge in variable degrees.	
Orphanet:1410	Uncombable hair syndrome	PADI3;TGM3	2	Uncombable hair syndrome (UHS), or pili trianguli et canaliculi, is a rare scalp hair shaft dysplasia.	Rare genetic skin disease
Orphanet:1412	Tarsal-carpal coalition syndrome	NOG	1	Tarsal-carpal coalition syndrome is characterised by fusion of the carpals, tarsals, and phalanges.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:1416	Familial calcium pyrophosphate deposition	ANKH	1	Familial calcium pyrophosphate deposition (CPPD) is a chronic inherited arthropathy characterized by chondrocalcinosis (CC; i.e. cartilage calcification), often associated with recurrent acute calcium pyrophosphate (CPP) crystal arthritis and polyarticular osteoarthritis (OA).	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:1394	Cerebrofaciothoracic dysplasia	TMCO1	1	Cerebro-facio-thoracic dysplasia or Pascual-Castroviejo syndrome type 1 is a rare syndrome characterized by facial dysmorphism, intellectual deficit and costovertebral abnormalities.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:141074	External auditory canal aplasia/hypoplasia	TSHZ1	1	A rare, otorhinolaryngological malformation characterized by failure in development of the external ear canal resulting in variable degree of malformations ranging from complete absence to mild stenosis and malformation of the middle ear. It is typically unilateral, it manifests with hearing loss on the affected side, and might be associated with microtia or hypoplastic pinna, an aberrant facial nerve course, and cholesteatoma.	Rare genetic developmental defect during embryogenesis;Genetic otorhinolaryngologic disease
Orphanet:174	Metaphyseal chondrodysplasia, Schmid type	COL10A1	1	Schmid metaphyseal chondrodysplasia is a rare disorder characterized by moderately short stature with short limbs, coxa vara, bowlegs and an abnormal gait.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:1425	Desbuquois syndrome	CANT1;XYLT1	2	Desbuquois syndrome (DBQD) is an osteochondrodysplasia characterized by severe micromelic dwarfism, facial dysmorphism, joint laxity with multiple dislocations, vertebral and metaphyseal abnormalities and advanced carpotarsal ossification. Two forms have been distinguished on the basis of the presence (type 1) or the absence (type 2) of characteristic hand anomalies. A variant form of DBQD, Kim variant (see these terms), has also been described and is characterized by short stature and articular, minor facial and significant hand anomalies.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease
Orphanet:156728	Spondyloepimetaphyseal dysplasia, matrilin-3 type	MATN3	1	Spondyloepimetaphyseal dysplasia, matrilin-3 type is characterized by disproportionate early-onset dwarfism, bowing of the lower limbs, short, wide and stocky long bones with severe epiphyseal and metaphyseal changes, lumbar lordosis, hypoplastic iliac bones, flat ovoid vertebral bodies and normal hands.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:163	Hereditary hyperferritinemia-cataract syndrome	FTL	1	Hereditary hyperferritinemia with congenital cataracts is characterized by the association of early onset (although generally absent at birth) cataract with persistently raised plasma ferritin concentrations in the absence of iron overload.	Rare genetic eye disease
Orphanet:1393	Cerebrocostomandibular syndrome	SNRPB	1	Cerebro-costo-mandibular syndrome (CCMS) is characterized at birth by posterior rib gaps and orofacial anomalies reminiscent of Pierre Robin syndrome (see this term) that include palatal defects (short hard palate, absent soft palate, absent uvula), micrognathia and glossoptosis.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:157820	Cold-induced sweating syndrome	KLHL7;CRLF1;CLCF1	3	Cold-induced sweating syndrome (CISS) is characterized by profuse sweating (involving the chest, face, arms and trunk) induced by cold ambient temperature.	Rare genetic neurological disorder
Orphanet:157798	Hyperplastic polyposis syndrome	RNF43	1	Hyperplastic polyposis syndrome is a rare, genetic intestinal disease characterized by the presence of multiple (usually large) hyperplastic/serrated colorectal polyps, usually with a pancolonic distribution. Histology reveals hyperplastic polyps, sessile serrated adenomas (most common), traditional serrated adenomas or mixed polyps. It is associated with an increased personal and familial (first-degree relatives) risk of colorectal cancer.	Rare genetic gastroenterological disease;Inherited cancer-predisposing syndrome
Orphanet:157801	Mesoaxial synostotic syndactyly with phalangeal reduction	BHLHA9	1	Mesoaxial synostotic syndactyly (MSSD) with phalangeal reduction is a novel and distinct form of non-syndromic syndactyly including complete syndactyly of the 3rd and 4th fingers with synostoses of the corresponding metacarpals and associated single phalanges, syndactyly of the 2nd and 3rd toes and 5th finger clinodactyly.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:1388	Catel-Manzke syndrome	TGDS	1	Catel-Manzke syndrome is a rare bone disease characterized by bilateral hyperphalangy and clinodactyly of the index finger typically in association with Pierre Robin sequence (see this term) comprising micrognathia, cleft palate and glossoptosis.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:157791	Epithelioid hemangioendothelioma	TFE3;CAMTA1;YAP1;WWTR1	4	NA	Rare genetic developmental defect during embryogenesis
Orphanet:1387	Cataract-intellectual disability-hypogonadism syndrome	RAB3GAP1;RAB3GAP2	2	This syndrome is characterized by the association of intellectual deficit, congenital cataract, and hypogonadotropic hypogonadism.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility;Rare genetic eye disease
Orphanet:157794	Hereditary mixed polyposis syndrome	BMPR1A;GREM1	2	Hereditary mixed polyposis syndrome (HMPS) describes an autosomal dominantly inherited large-bowel disease characterized by the presence of a mixture of hyperplastic, atypical juvenile and adenomatous polyps that are associated with an increased risk of developing colorectal cancer if left untreated.	Rare genetic gastroenterological disease;Inherited cancer-predisposing syndrome
Orphanet:157769	Situs ambiguus	PKD1L1;ZIC3;ACVR2B;LEFTY2;NODAL;CFAP53;MMP21;CFC1	8	A rare, genetic, developmental defect during embryogenesis characterized by a partial mirror-image transposition of intra-thoracic and/or intra-abdominal organs across the left-right axis of the body. Intra-organ variations and other malformations, such as ciliary motricity anomalies (e.g. Kartagener syndrome), biliary atresia and cardiac defects, are frequently associated. Left (polysplenia syndrome) or right (asplenia syndrome) isomerism are usually observed.	Rare genetic developmental defect during embryogenesis
Orphanet:157716	Late infantile CACH syndrome	EIF2B1;EIF2B2;EIF2B3;EIF2B4;EIF2B5	5	NA	Rare genetic neurological disorder
Orphanet:157719	Juvenile or adult CACH syndrome	EIF2B1;EIF2B2;EIF2B3;EIF2B4;EIF2B5	5	NA	Rare genetic neurological disorder
Orphanet:157713	Congenital or early infantile CACH syndrome	EIF2B1;EIF2B2;EIF2B3;EIF2B4;EIF2B5	5	NA	Rare genetic neurological disorder
Orphanet:157215	Hereditary hypophosphatemic rickets with hypercalciuria	SLC34A3	1	Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a hereditary renal phosphate-wasting disorder characterized by hypophosphatemia and hypercalciuria associated with rickets and/or osteomalacia.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic endocrine disease;Rare genetic renal disease
Orphanet:1377	Cataract-microcornea syndrome	CRYAA;CRYBA4;CRYBB2;CRYGC;CRYGD;GJA8;CRYBB1;MAF	8	Cataract-microcornea syndrome is characterized by the association of congenital cataract and microcornea without any other systemic anomaly or dysmorphism.	Rare genetic eye disease
Orphanet:1328	Camurati-Engelmann disease	TGFB1	1	Camurati-Englemann disease (CED) is a rare, clinically variable bone dysplasia syndrome characterized by hyperostosis of the long bones, skull, spine and pelvis, associated with severe pain in the extremities, a wide-based waddling gait, joint contractures, muscle weakness and easy fatigability. Camurati-Englemann disease (CED) is a rare, clinically variable bone dysplasia syndrome characterized by hyperostosis of the long bones, skull, spine and pelvis, associated with severe pain in the extremities, a wide-based waddling gait, joint contractures, muscle weakness and easy fatigability.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:1338	Heart defect-tongue hamartoma-polysyndactyly syndrome	WDPCP	1	A rare, genetic, multiple congenital anomalies syndrome characterized by congenital heart defects (e.g. coarctation of the aorta with or without atrioventricular canal and subaortic stenosis), associated with tongue hamartomas, postaxial hand polydactyly and toe syndactyly.	Rare genetic developmental defect during embryogenesis
Orphanet:1340	Cardiofaciocutaneous syndrome	BRAF;KRAS;MAP2K1;MAP2K2	4	Cardiofaciocutaneous (CFC) syndrome is a RASopathy characterized by craniofacial dysmorphism, congenital heart disease, dermatological abnormalities (most commonly hyperkeratotic skin and sparse, curly hair), growth retardation and intellectual disability.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic cardiac disease;Rare genetic skin disease;RASopathy
Orphanet:2856	Persistent Müllerian duct syndrome	AMH;AMHR2	2	Persistent Müllerian duct syndrome (PMDS) is a rare disorder of sex development (DSD) characterized by the persistence of Müllerian derivatives, the uterus and/or fallopian tubes, in otherwise normally virilized boys.	Genetic infertility
Orphanet:1766	Dysequilibrium syndrome	VLDLR;WDR81;CA8;ATP8A2;TUBB2B	5	Dysequilibrium syndrome (DES) is a non-progressive cerebellar disorder characterized by ataxia associated with an intellectual disability, delayed ambulation and cerebellar hypoplasia.	Rare genetic neurological disorder
Orphanet:1777	Temtamy syndrome	C12ORF57	1	Temtamy syndrome is a very rare congenital genetic neurological disorder characterized by agenesis/hypoplasia of corpus callosum with developmental abnormalities, ocular disorders, and variable craniofacial and skeletal abnormalities.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:1772	45,X/46,XY mixed gonadal dysgenesis	SRY	1	45,X/46,XY mixed gonadal dysgenesis (45,X/46,XY MGD) is a disorder of sex development (DSD) associated with a numerical sex chromosome abnormality resulting from Y-chromosome mosaicism and leading to abnormal gonadal development.	Rare chromosomal anomaly;Genetic infertility;Rare genetic gynecological and obstetrical diseases;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease
Orphanet:1782	Dysosteosclerosis	SLC29A3	1	Dysosteosclerosis is a skeletal dysplasia characterized by progressive osteosclerosis and platyspondyly.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:1788	Acrofacial dysostosis, Rodríguez type	SF3B4	1	 or shortly after birth.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:139441	Hypomyelination with atrophy of basal ganglia and cerebellum	TUBB4A;UFM1	2	A rare disorder characterized by slowly progressive spasticity, extrapyramidal movement disorders (dystonia, choreoathetosis and rigidity), cerebellar ataxia, moderate to severe cognitive deficit, and anarthria/dysarthria.	Rare genetic neurological disorder
Orphanet:859	Transcobalamin deficiency	TCN2	1	Transcobalamin deficiency (TC) is a disorder of cobalamin transport that usually presents during the first few months of life and is characterized by megaloblastic anemia, failure to thrive, vomiting, weakness and pancytopenia.	Rare genetic immune disease;Rare inborn errors of metabolism;Rare genetic hematologic disease
Orphanet:1573	Hypotrichosis with juvenile macular degeneration	CDH3	1	Hypotrichosis with juvenile macular degeneration (HJMD) is a very rare syndrome characterized by sparse and short hair from birth followed by progressive macular degeneration leading to blindness.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:726	Alpers-Huttenlocher syndrome	POLG	1	A cerebrohepatopathy and a rare and severe form of mitochondrial DNA (mtDNA) depletion syndrome characterized by the triad of progressive developmental regression, intractable seizures, and hepatic failure.	Rare genetic neurological disorder;Rare genetic hepatic disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic gastroenterological disease
Orphanet:139455	Autosomal recessive bestrophinopathy	BEST1	1	A rare retinal dystrophy, characterized by central visual loss in the first 2 decades of life, associated with an absent electrooculogram (EOG) light rise and a reduced electroretinogram (ERG).	Rare genetic eye disease
Orphanet:139466	SERKAL syndrome	WNT4	1	SERKAL (SEx Reversion, Kidneys, Adrenal and Lung dysgenesis) syndrome is characterised by female to male sex reversal and developmental anomalies of the kidneys, adrenal glands and lungs.	Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease
Orphanet:1596	Distal monosomy 15q	MCTP2	1	Distal monosomy 15q is a rare chromosomal anomaly syndrome characterized by pre- and postnatal growth restriction, developmental delay, variable degrees of intellectual disability, hand and foot anomalies (e.g. brachy-/clinodactyly, talipes equinovarus, nail hypoplasia, proximally placed digits) and mild craniofacial dysmorphism (incl. microcephaly, triangular face, broad nasal bridge, micrognathia). Neonatal lymphedema, heart malformations, aplasia cutis congenita, aortic root dilatation, and autistic spectrum disorder have also been reported.	Rare chromosomal anomaly
Orphanet:139471	Microphthalmia with brain and digit anomalies	BMP4	1	 gene, which has already been shown to play a role in eye development.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:139474	17q11.2 microduplication syndrome	NF1	1	17q11.2 microduplication syndrome is characterized by dysmorphic features and intellectual deficit.	Rare chromosomal anomaly;Rare genetic neurological disorder
Orphanet:1617	2q24 microdeletion syndrome	TBR1	1	2q24 microdeletion syndrome is a chromosomal anomaly consisting of a partial long arm deletion of chromosome 2 and characterized clinically by a wide range of manifestations (depending on the specific region deleted) which can include seizures, microcephaly, dysmorphic features, cleft palate, eye abnormalities (coloboma, cataract and microphthalmia), growth retardation, failure to thrive, heart defects, limb anomalies, developmental delay and autism.	Rare genetic eye disease;Rare chromosomal anomaly
Orphanet:139480	Autosomal recessive spastic paraplegia type 39	PNPLA6	1	This syndrome is characterised by progressive spastic paraplegia and distal muscle wasting.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:1606	1p36 deletion syndrome	RERE;GABRD;SKI;KCNAB2;PRDM16	5	1p36 deletion syndrome is a chromosomal anomaly characterized by distinctive facial dysmorphic features, hypotonia, developmental delay, intellectual disability, seizures, heart defects, hearing impairment and prenatal onset growth deficiency.	Rare genetic cardiac disease;Rare genetic neurological disorder;Rare chromosomal anomaly
Orphanet:139485	Autosomal recessive ataxia due to ubiquinone deficiency	COQ8A	1	This syndrome is characterised by childhood-onset progressive ataxia and cerebellar atrophy.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:139491	Hemochromatosis type 4	SLC40A1;SLC40A1	2	Hemochromatosis type 4 (also called ferroportin disease) is a form of rare hereditary hemochromatosis (HH; see this term), a group of diseases characterized by excessive tissue iron deposition of genetic origin.	Rare genetic hepatic disease;Rare inborn errors of metabolism
Orphanet:139515	Charcot-Marie-Tooth disease type 4J	FIG4	1	Charcot-Marie-Tooth disease type 4J is a subtype of Charcot-Marie-Tooth disease type 4 characterized by childhood- to adulthood-onset of variably severe, rapidly progressive, axonal and demyelinating sensorimotor neuropathy typically manifesting with delayed motor development, proximal and distal asymmetric muscle weakness and atrophy of the lower and upper extremities, severe motor dysfunction with mildly reduced sensory impairment, and areflexia. Nerve conduction velocities range from very mildly to severely reduced.	Rare genetic neurological disorder
Orphanet:139512	Neuropathy with hearing impairment	GJB3	1	This syndrome is characterized by the association of sensorineural hearing impairment and peripheral neuropathy.	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder
Orphanet:139525	Distal hereditary motor neuropathy type 2	HSPB1;HSPB8;HSPB3;FBXO38	4	NA	Rare genetic neurological disorder
Orphanet:1658	Absence of fingerprints-congenital milia syndrome	SMARCAD1	1	A rare syndrome syndrome characterized by neonatal blisters and milia (small white papules, especially on the face) and congenital absence of dermatoglyphics on the hands and feet. It has been reported in two kindreds (one of which contained 13 affected individuals spanning three generations) and in an unrelated individual. Some affected patients also showed bilateral partial flexion contractures of the fingers and toes, and webbing of the toes. The syndrome is inherited as an autosomal dominant trait.	Rare genetic skin disease
Orphanet:139536	Distal hereditary motor neuropathy type 5	REEP1;BSCL2;GARS	3	NA	Rare genetic neurological disorder
Orphanet:139557	X-linked distal spinal muscular atrophy type 3	ATP7A	1	X-linked distal spinal muscular atrophy type 3 is a rare distal hereditary motor neuropathy characterized by slowly progressive atrophy and weakness of distal muscles of hands and feet with normal deep tendon reflexes or absent ankle reflexes and minimal or no sensory loss, sometimes mild proximal weakness in the legs and feet and hand deformities in males.	Rare genetic neurological disorder
Orphanet:1662	Restrictive dermopathy	ZMPSTE24;LMNA	2	A congenital genodermatosis with skin/mucosae involvement, characterized by very tight and thin skin with erosions and scaling, associated to a typical facial dysmorphism, arthrogryposis multiplex, fetal akinesia or hypokinesia deformation sequence (FADS) and pulmonary hypoplasia without neurological abnormalities.	Rare genetic developmental defect during embryogenesis;Laminopathy
Orphanet:139552	Distal hereditary motor neuropathy, Jerash type	SIGMAR1	1	A rare, genetic, neuromuscular disease characterized by progressive, symmetrical, moderate to severe, distal muscle weakness and atrophy, without sensory involvement, first affecting the lower limbs (towards the end of the first decade) and then involving (within two years) the upper extremities. Patients typically develop foot drop, pes varus, hammer toes and claw hands. Pyramidal tract signs (such as brisk knee reflexes and positive Babinski sign) with absent ankle reflexes are initially associated but regress as disease stabilizes (~10 years after onset).	Rare genetic neurological disorder
Orphanet:139583	X-linked hereditary sensory and autonomic neuropathy with deafness	AIFM1	1	This syndrome is characterized by the association of an axonal sensory and autonomic neuropathy with hearing loss.	Rare genetic neurological disorder
Orphanet:1667	Wolcott-Rallison syndrome	EIF2AK3	1	Wolcott-Rallison syndrome (WRS) is a very rare genetic disease, characterized by permanent neonatal diabetes mellitus (PNDM) with multiple epiphyseal dysplasia and other clinical manifestations, including recurrent episodes of acute liver failure.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic endocrine disease
Orphanet:139578	Mutilating hereditary sensory neuropathy with spastic paraplegia	CCT5	1	This syndrome is characterized by the association of an axonal sensory and autonomic neuropathy with spastic paraplegia.	Rare genetic neurological disorder
Orphanet:139589	Distal hereditary motor neuropathy type 7	DCTN1;SLC5A7	2	A rare, slowly progressive genetic peripheral neuropathy characterized by distal atrophy and weakness affecting the upper limbs (with a predilection for the thenar eminence) and subsequently the lower limbs, associated with uni- or bilateral vocal cord paresis leading to hoarse voice and breathing difficulties, and facial weakness.	Rare genetic neurological disorder
Orphanet:140917	Stapes ankylosis with broad thumbs and toes	NOG	1	Stapes ankylosis with broad thumbs and toes is a very rare genetic bone disorder characterized by ankylosis of stapes, broad thumbs and halluces, conductive hearing loss and hyperopia.	Genetic otorhinolaryngologic disease
Orphanet:140922	Autosomal recessive limb-girdle muscular dystrophy type 2J	TTN	1	A form of limb-girdle muscular dystrophy that usually has a childhood onset (but can range from the first to third decade of life) of severe progressive proximal weakness, eventually involving the distal muscles. Some patients may remain ambulatory but most are wheelchair dependant 20 years after onset.	Rare genetic neurological disorder
Orphanet:1545	Crisponi syndrome	CRLF1;CLCF1	2	Crisponi syndrome (CS) is a severe disorder characterized by muscular contractions at birth, intermittent hyperthermia, facial abnormalities and camptodactyly.	Rare genetic neurological disorder
Orphanet:140905	Hyperlipidemia due to hepatic triacylglycerol lipase deficiency	LIPC	1	Hyperlipidemia due to hepatic triacylglycerol lipase deficiency is a rare, genetic hyperalphalipoproteinemia disorder characterized by elevated plasma cholesterol and triglyceride (TG) levels with a marked TG enrichment of low- and high-density lipoproteins (HDL), presence of circulating beta-very low density lipoproteins and elevated HDL cholesterol levels, in the presence of a very low, or undetectable, postheparin plasma hepatic lipase activity. Premature atherosclerosis and/or coronary heart disease may be associated.	Rare inborn errors of metabolism;Rare genetic endocrine disease
Orphanet:1540	Jackson-Weiss syndrome	FGFR2	1	Jackson-Weiss syndrome (JWS) is a rare genetic disorder characterized by foot malformations (tarsal and metatarsal fusions; short, broad, medially deviated great toes) and in some patients craniosynostosis with facial anomalies. Hands are normal in affected patients.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:140908	Brachydactyly type B2	NOG	1	A rare, genetic congenital limb malformation disorder characterized by hypoplasia/aplasia of distal and/or middle phalanges in fingers and toes II-V (frequently severe in fingers/toes IV-V, milder in fingers/toes II-III) in association with proximal, and occasionally distal, symphalangism, fusion of carpal/tarsal bones and partial cutaneous syndactyly. Additional reported features include proximal placement of thumbs, sensorineural hearing loss and farsightedness.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:140952	Syndactyly-telecanthus-anogenital and renal malformations syndrome	CCNQ	1	This syndrome is characterised by the association of toe syndactyly, facial dysmorphism including telecanthus (abnormal distance between the eyes) and a broad nasal tip, urogenital malformations and anal atresia.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:140957	Autosomal dominant macrothrombocytopenia	GFI1B;GP1BB;TPM4;ITGA2B;ITGB3;TUBB1;ACTN1	7	This syndrome is characterized by congenital thrombocytopenia associated with the presence of large platelets.	Rare genetic hematologic disease
Orphanet:140944	CLOVES syndrome	PIK3CA	1	CLOVE syndrome is characterized by Congenital Lipomatous Overgrowth, progressive, complex and mixed truncal Vascular malformations, and Epidermal nevi.	Rare genetic tumor;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic skin disease
Orphanet:1555	Cutis gyrata-acanthosis nigricans-craniosynostosis syndrome	FGFR2	1	Cutis gyrata-acanthosis nigricans-craniosynostosis syndrome, also known as Beare-Stevenson syndrome (BSS), is a severe form of syndromic craniosynostosis, characterized by a variable degree of craniosynostosis, with cloverleaf skull reported in over 50% of cases, cutis gyrata, corduroy-like linear striations in the skin, acanthosis nigricans, skin tags, and choanal stenosis or atresia). Additional features include facial features similar to Crouzon disease, ear defects (conductive hearing loss, posteriorly angulated ears, stenotic auditory canals, preauricular furrows, and narrow ear canals), hirsutism, a prominent umbilical stump, and genitorurinary anomalies (anteriorly placed anus, hypoplasic labia, hypospadias). BSS is associated with a poor outcome as patients present an elevated risk for sudden death in their first year of life. Significant developmental delay and intellectual disability are observed in most patients who survive infancy.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic bone disease
Orphanet:140941	Short stature due to primary acid-labile subunit deficiency	IGFALS	1	Short stature due to primary acid-labile subunit (ALS) deficiency is characterized by moderate postnatal growth deficit, markedly low circulating levels of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3), and hyperinsulinemia, in the absence of growth hormone (GH) deficiency or GH insensitivity.	Rare genetic endocrine disease
Orphanet:140927	Benign familial neonatal-infantile seizures	SCN2A;KCNQ2	2	 gene (2q24.3), encoding the voltage-gated sodium channel alpha-subunit Na(V)1.2. Transmission is autosomal dominant.	Rare genetic neurological disorder
Orphanet:1553	Curry-Jones syndrome	SMO	1	Curry-Jones syndrome is a form of syndromic craniosynostosis characterized by unilateral coronal craniosynostosis or multiple suture synostosis associated with complete or partial agenesis of the corpus callosum, preaxial polysyndactyly and syndactyly of hands and/or feet, along with anomalies of the skin (characteristic pearly white areas that become scarred and atrophic, abnormal hair growth around the eyes and/or cheeks, and on the limbs), eyes (iris colobomas, microphthalmia,) and intestine (congenital short gut, malrotation, dysmotility, chronic constipation, bleeding and myofibromas). Developmental delay and variable degrees of intellectual disability may also be observed. Multiple intra-abdominal smooth muscle hamartomas, trichoblastoma of the skin, occipital meningoceles and development of desmoplastic medulloblastoma have been reported.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:140969	Saldino-Mainzer syndrome	IFT140;IFT172	2	Saldino-Mainzer syndrome is characterised by the association of renal disease, retinal pigmentary dystrophy, cerebellar ataxia and skeletal dysplasia.	Rare genetic renal disease;Rare genetic eye disease;Ciliopathy;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:140966	Palmoplantar keratoderma, Nagashima type	SERPINB7	1	Keratosis, Nagashima-type is a transgressive and nonprogressive palmoplantar keratoderma resembling a mild form of mal de Meleda (see this term).	Serpinopathy;Rare genetic skin disease
Orphanet:140963	Bilateral microtia-deafness-cleft palate syndrome	HOXA2	1	This syndrome is characterized by the association of bilateral microtia with severe to profound hearing impairment, and cleft palate.	Genetic otorhinolaryngologic disease;Rare genetic developmental defect during embryogenesis
Orphanet:382	Guanidinoacetate methyltransferase deficiency	GAMT	1	Guanidinoacetate methyltransferase (GAMT) deficiency is a creatine deficiency syndrome characterized by global developmental delay/intellectual disability (DD/ID), prominent speech delay, autistic/hyperactive behavioral disorders, seizures, and various types of pyramidal and/or extra-pyramidal manifestations.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:742	Prolidase deficiency	PEPD	1	Prolidase deficiency is an inherited disorder of peptide metabolism characterized by severe skin lesions, recurrent infections (involving mainly the skin and respiratory system), dysmorphic facial features, variable cognitive impairment, and splenomegaly.	Rare genetic neurological disorder;Rare genetic skin disease;Rare inborn errors of metabolism
Orphanet:1571	Knobloch syndrome	COL18A1	1	Knobloch syndrome (KS) is defined by vitreoretinal and macular degeneration, and occipital encephalocele.	Rare genetic eye disease
Orphanet:1568	X-linked intellectual disability-Dandy-Walker malformation-basal ganglia disease-seizures syndrome	AP1S2	1	X-linked Dandy-Walker malformation with intellectual disability, basal ganglia disease and seizures (XDIBS), or Pettigrew syndrome is a central nervous system malformation characterized by severe intellectual deficit, early hypotonia with progression to spasticity and contractures, choreoathetosis, seizures, dysmorphic face (long face with prominent forehead), and brain imaging abnormalities such as Dandy-Walker malformation (see this term), and iron deposition.	Rare genetic eye disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:1497	X-linked complicated corpus callosum dysgenesis	L1CAM	1	X-linked complicated corpus callosum dysgenesis is a historical term used to describe a phenotype now considered to be part of the L1 clinical spectrum (L1 syndrome, see this term). The disorder is characterized by variable spastic paraplegia, mild to moderate intellectual deficit, and dysplasia, hypoplasia or aplasia of the corpus callosum.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:140436	Primary intraosseous venous malformation	ELMO2	1	Primary intraosseous venous malformation is a rare, genetic vascular anomaly characterized by severe blood vessel expansion (most frequently within the craniofacial bones) with painless bone enlargement (usually of mandibule, maxilla and/or orbital, nasal, and frontal bones), typically resulting in facial asymmetry and contour deformation. Midline abnormalities, such as diastasis recti, supraumbilical raphe, and hiatus hernia, are commonly associated. Additional features reported include gingival bleeding, ectopic tooth eruption, exophthalmos, loss of vision, nausea, and vomiting.	Rare genetic bone disease
Orphanet:1493	Vici syndrome	EPG5	1	Vici syndrome is a very rare and severe congenital multisystem disorder characterized by the principal features of agenesis of the corpus callosum, cataracts, oculocutaneous hypopigmentation, cardiomyopathy and combined immunodeficiency.	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic cardiac disease;Rare genetic immune disease;Rare genetic neurological disorder;Rare genetic skin disease
Orphanet:1509	Coxopodopatellar syndrome	TBX4	1	Small patella syndrome (SPS) is a very rare benign bone dysplasia affecting skeletal structures of the lower limb and the pelvis.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:1507	Autosomal recessive Robinow syndrome	ROR2;NXN	2	Autosomal recessive Robinow syndrome (RRS) is the less common type of Robinow syndrome (RS, see this term) characterized by short-limb dwarfism, costovertebral segmentation defects and abnormalities of the head, face and external genitalia.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:1517	Hypertrichotic osteochondrodysplasia, Cantu type	ABCC9;KCNJ8	2	Cantu syndrome is a rare disorder characterized by congenital hypertrichosis, osteochondrodysplasia, cardiomegaly, and dysmorphism.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:1519	Hypertelorism, Teebi type	SPECC1L	1	Teebi type hypertelorism is a rare genetic disease characterized by hypertelorism with facial features that can closely resemble craniofrontonasal dysplasia (see this term), such as prominent forehead, widow's peak, heavy and broad eyebrows, long palpebral fissures, ptosis, high and broad nasal bridge, short nose, low-set ears, natal teeth, thin upper lip and a grooved chin, as well as limb (i.e. fifth-finger clinodactyly, pes adductus, mild interdigital webbing), urogenital (i.e. bilateral cryptorchidism and shawl scrotum in males) and umbilical (i.e. hernia/small omphalocele) anomalies and cardiac (i.e. ventricular or atrial septal defect, patent ductus arteriosus) defects. Additional findings such as polycystic kidneys and iridochorioretinal colobomas have also been reported and psychomotor development is normal. The facial features can also resemble Aarskog and Opitz G/BBB syndromes (see these terms).	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:1520	Craniofrontonasal dysplasia	EFNB1	1	Craniofrontonasal dysplasia is an X-linked malformation syndrome characterized by facial asymmetry (particularly orbital), body asymmetry, midline defects (hypertelorism, frontal bossing, broad grooved or bifid nasal tip, cleft lip and/or palate, high arched palate), skeletal anomalies (clavicle pseudoarthrosis, coronal craniosynostosis, various digital and limb anomalies including syndactyly, clinodactyly of the 5th finger, broad thumbs) and ectodermal dysplasias (dental anomalies, grooved nails, wiry hair). Contrary to most X-linked disorders, females are much more severely affected whereas males are asymptomatic or present with a mild phenotype, frequently only displaying hypertelorism.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:1513	Craniodiaphyseal dysplasia	SOST	1	Craniodiaphyseal dysplasia is a rare sclerotic bone disorder with a variable phenotypic expression with massive generalized hyperostosis and sclerosis, particularly of the skull and facial bones, that may lead to severe deformity.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:140481	Autosomal dominant slowed nerve conduction velocity	ARHGEF10	1	 gene.	Rare genetic neurological disorder
Orphanet:1515	Cranioectodermal dysplasia	IFT122;WDR35;IFT43;WDR19;IFT52	5	Cranioectodermal dysplasia (CED) is a rare developmental disorder characterized by congenital skeletal and ectodermal defects associated with dysmorphic features, nephronophthisis, hepatic fibrosis and ocular anomalies (mainly retinitis pigmentosa).	Rare genetic renal disease;Rare genetic eye disease;Ciliopathy;Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:1529	Craniofacial-deafness-hand syndrome	PAX3	1	Craniofacial-deafness-hand syndrome (CDHS) is an autosomal dominant disorder, described in one family to date, characterized by characteristic facial features (flat facial profile with normal calvarium, hypertelorism, small downslanting palpebral fissures, hypoplastic nose with button tip and slitlike nares, small ''pursed'' mouth), profound sensorineural deafness, and ulnar deviations and contractures of the hand. CDHS is thought to be an allelic variant of Waardenburg syndrome (see this term) that can be distinguished from the latter by its imaging findings and distinct facial features.	Genetic otorhinolaryngologic disease;Rare genetic developmental defect during embryogenesis
Orphanet:1522	Craniometaphyseal dysplasia	ANKH;GJA1	2	Craniometaphyseal dysplasia (CMD) is a very rare genetic bone disease characterized by progressive diffuse hyperostosis of cranial bones causing facial dysmorphism and functional repercussions, and metaphyseal widening of long bones.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:1525	Cranio-osteoarthropathy	HPGD	1	Cranio-osteoarthropathy (COA) is a form of primary hypertrophic osteoarthropathy (see this term) characterized by delayed closure of the cranial sutures and fontanels, digital clubbing, arthropathy, and periostosis.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:1824	Lowry-Wood syndrome	RNU4ATAC	1	A rare disorder characterized by the association of epiphyseal dysplasia, short stature, microcephaly and, in the first reported cases, congenital nystagmus. So far, less than 10 cases have been described in the literature. Variable degrees of intellectual deficit have also been reported. Other occasional features include retinitis pigmentosa and coxa vara. Transmission appears to be autosomal recessive.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:1955	Spinocerebellar ataxia type 34	ELOVL4	1	A subtype of autosomal dominant cerebellar ataxia type I (ADCA type I), characterized by papulosquamous, ichthyosiform plaques on the limbs appearing shortly after birth and later manifestations including progressive ataxia, dysarthria, nystagmus and decreased reflexes.	Rare genetic neurological disorder;Rare genetic skin disease
Orphanet:1956	OBSOLETE: Erythromelalgia	SCN9A	1	NA	NA
Orphanet:2209	Maternal phenylketonuria	PAH	1	A rare disorder of phenylalanine metabolism, an inborn error of amino acid metabolism, characterized by the development of microcephaly, growth retardation, congenital heart disease, facial dysmorphism and intellectual disability in nonphenylketonuric offspring of mothers with excess phenylalanine (Phe) concentrations.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:1896	EEC syndrome	TP63	1	EEC syndrome is a genetic developmental disorder characterized by ectrodactyly, ectodermal dysplasia, and orofacial clefts (cleft lip/palate).	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease;Rare genetic skin disease
Orphanet:1897	EEM syndrome	CDH3	1	, 16q22.1).	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease
Orphanet:1807	Focal facial dermal dysplasia type III	TWIST2	1	Focal facial dermal dysplasia type III (FFDD3) is a rare focal facial dermal dysplasia (FFDD; see this term), characterized primarily by congenital bitemporal scar-like depressions and a typical, but variable facial dysmorphism, which may include distichiasis (upper lids) or lacking eyelashes, slanted eyebrows and a flattened and/or bulbous nasal tip and other features such as a low frontal hairline, sparse hair, redundant skin, epicanthal folds, low-set dysplastic ears, blepharitis and conjunctivitis.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:1873	Jalili syndrome	CNNM4	1	Jalili syndrome is characterized by the association of amelogenesis imperfecta (AI; see this term) and cone-rod retinal dystrophy (CORD; see this term).	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:1879	Melorheostosis with osteopoikilosis	LEMD3	1	Melorheostosis with osteopoikilosis is a rare sclerosing bone dysplasia, combining the clinical and radiological features of melorheostosis and osteopoikilosis (see these terms), that has been reported in some families with osteopoikilosis and that is characterized by a variable presentation of limb pain and deformities.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:1872	Cone rod dystrophy	RPGR;PRPH2;PITPNM3;OPN1MW;CRX;NMNAT1;C8ORF37;CDHR1;ABCA4;RIMS1;RPGRIP1;CACNA1F;CNGA3;AIPL1;GUCA1A;GUCY2D;OPN1LW;RAX2;SEMA4A;PROM1;CACNA2D4;ADAM9;UNC119;RAB28;POC1B;DRAM2;TTLL5;ATF6	28	A rare genetic isolated inherited retinal disorder characterized by primary cone degeneration with significant secondary rod involvement, with a variable fundus appearance. Typical presentation includes decreased visual acuity, central scotoma, photophobia, color vision alteration, followed by night blindness and loss of peripheral visual field.	Rare genetic eye disease;Ciliopathy
Orphanet:1871	Progressive cone dystrophy	PDE6C;GNAT2;CNGB3;GUCA1A	4	NA	Rare genetic eye disease;Ciliopathy
Orphanet:1860	Thanatophoric dysplasia type 1	FGFR3	1	Thanatophoric dysplasia type 1 (TD1) is a form of TD (see this term) characterized by short, bowed femurs, micromelia, narrow thorax, and brachydactyly.	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:1865	Dyssegmental dysplasia, Silverman-Handmaker type	HSPG2	1	Dyssegmental dysplasia, Silverman-Handmaker type is a rare, genetic, primary bone dysplasia disorder, and lethal form of neonatal short-limbed dwarfism, characterized by anisospondyly, severe short stature and limb shortening, metaphyseal flaring and distinct dysmorphic features (i.e. flat facial appearance, abnormal ears, short neck, narrow thorax). Additional features may include other skeletal findings (e.g. joint contractures, bowed limbs, talipes equinovarus) and urogenital and cardiovascular abnormalities.	Rare genetic bone disease;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:1830	Schimke immuno-osseous dysplasia	SMARCAL1	1	Schimke immuno-osseous dysplasia (SIOD) is a multisystem disorder characterized by spondyloepiphyseal dysplasia and disproportionate short stature, facial dysmorphism, T-cell immunodeficiency, and glomerulonephritis with nephrotic syndrome.	Rare genetic renal disease;Rare genetic immune disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic odontologic disease
Orphanet:1802	Ghosal hematodiaphyseal dysplasia	TBXAS1	1	Ghosal hematodiaphyseal dysplasia syndrome (GHDD) is a rare disorder characterized by increased bone density (predominantly diaphyseal) and aregenerative corticosteroid-sensitive anemia.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2128	Isolated hemihyperplasia	IGF2;H19;KCNQ1OT1	3	Isolated hemihyperplasia is a rare overgrowth syndrome characterized by an asymmetric regional body overgrowth, involving at least one limb, and associated with an increased risk of developing embryonal tumors, principally nephroblastoma (see this term) and hepoblastoma.	Rare genetic developmental defect during embryogenesis;Inherited cancer-predisposing syndrome
Orphanet:2136	Hennekam syndrome	CCBE1;FAT4;ADAMTS3	3	Hennekam syndrome is characterised by the association of lymphoedema, intestinal lymphangiectasia, intellectual deficit and facial dysmorphism.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic immune disease
Orphanet:2138	46,XX ovotesticular disorder of sex development	SOX9;SRY;NR5A1	3	A rare disorder of sex development (DSD) characterized by histologically confirmed testicular and ovarian tissue in an individual with a 46,XX karyotype.	Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease;Genetic infertility;Rare genetic gynecological and obstetrical diseases
Orphanet:2143	Donnai-Barrow syndrome	LRP2	1	A multiple congenital malformation syndrome characterized by typical facial dysmorphism, myopia and other ocular findings, hearing loss, agenesis of the corpus callosum, low-molecular-weight proteinuria, and variable intellectual disability. Congenital diaphragmatic hernia (CDH) and/or omphalocele are common.	Rare genetic developmental defect during embryogenesis
Orphanet:2148	Lissencephaly type 1 due to doublecortin gene mutation	DCX	1	Type 1 lissencephaly due to doublecortin (DCX) gene mutations is a semi-dominant X-linked disease characterised by intellectual deficiency and seizures that are more severe in male patients.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:2114	Hip dysplasia, Beukes type	UFSP2	1	Beukes familial hip dysplasia (BFHD) is a primary bone dysplasia, characterized by premature degenerative arthropathy of the hip. The disease presents with hip joint discomfort/pain and gait disturbances that usually develop in childhood and that progress to severe functional disability and limited mobility by early adulthood. Involvement of the vertebral bodies and other joints is minimal, height is not significantly reduced, and general health is unimpaired. Radiographically, the femoral heads are flattened and irregular and degenerative osteoarthritis develops in the hip joints, as evidenced by the presence of periarticular cysts, sclerosis, and joint space narrowing.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2117	Hartsfield syndrome	FGFR1	1	Hartsfield syndrome is a rare, genetic, developmental defect during embryogenesis malformation syndrome characterized by the association of variable degrees of holoprosencephaly and uni- or bilateral ectrodactyly of the hands and/or feet. Additional variable features, including facial dysmorphism (e.g. hypertelorism, short bulbous nose, long philtrum, dysplastic/low-set ears, cleft lip and palate, tented upper lip), other brain malformations (such as corpus callosum agenesis, absent septum pellucidum, absent olfactory bulbs/tracts, vermian hypoplasia), pituitary gland-related endocrine disorders (e.g. central diabetes insipidus, hypogonadotropic hypogonadism) and hypothalamic dysfunction, may be associated.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:376	Gordon syndrome	PIEZO2	1	Gordon syndrome, also known as distal arthrogryposis type 3, is an extremely rare multiple congenital malformation syndrome characterized by congenital contractures of hand and feet with variable degrees of severity of camptodactyly, clubfoot and, less frequently, cleft palate. Intelligence is normal but in some cases, additional abnormalities, such as short stature, kyphoscoliosis, ptosis, micrognathia, and cryptorchidism may also be present. Gordon syndrome, Marden-Walker syndrome and arthrogryposis with oculomotor limitation and electroretinal anomalies clinically and genetically overlap, and could represent variable expressions of the same condition.	Rare genetic developmental defect during embryogenesis
Orphanet:2092	Focal dermal hypoplasia	PORCN	1	A rare multiple congenital anomalies/dysmorphic syndrome characterized by abnormalities in ectodermal- and mesodermal-derived tissues, classically manifesting with skin abnormalities, limb defects, ocular malformations, and mild facial dysmorphism.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic skin disease
Orphanet:2098	Acromesomelic dysplasia, Grebe type	BMPR1B;GDF5	2	A rare autosomal recessive acromesomelic dysplasia characterized by severe dwarfism at birth, abnormalities confined to limbs, severe shortening and deformity of long bones, fusion or absence of carpal and tarsal bones, ball shaped fingers and, occasionally, polydactyly and absent joints. As seen in acromesomelic dysplasia, Hunter-Thomson type and acromesomelic dysplasia, Maroteaux Type, facial features and intelligence are normal.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:380	Greig cephalopolysyndactyly syndrome	GLI3	1	Greig cephalopolysyndactyly syndrome (GCPS) is a pleiotropic, multiple congenital anomaly syndrome.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2095	Gorlin-Chaudhry-Moss syndrome	SLC25A24	1	Gorlin-Chaudhry-Moss (GCM) syndrome is a multiple congenital anomaly syndrome characterized by craniofacial dysostosis, facial dysmorphism, conductive hearing loss, generalized hypertrichosis, and extremity, ocular and dental anomalies.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:158029	Sea-blue histiocytosis	APOE	1	NA	
Orphanet:157846	Neuroferritinopathy	FTL	1	Neuroferritinopathy is a late-onset type of neurodegeneration with brain iron accumulation (NBIA; see this term) characterized by progressive chorea or dystonia and subtle cognitive deficits.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:2067	GAPO syndrome	ANTXR1	1	A multiple congenital anomalies (MCA) syndrome involving connective tissue characterized by Growth retardation, Alopecia, Pseudoanodontia and Ocular manifestations.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic eye disease
Orphanet:2065	Galloway-Mowat syndrome	OSGEP;TP53RK;WDR73;NUP107;TPRKB;LAGE3;WDR4	7	A rare syndrome characterized by the association of nephrotic syndrome and central nervous system anomalies.	Rare genetic neurological disorder;Rare genetic renal disease
Orphanet:157941	Huntington disease-like 1	PRNP	1	A rare, genetic, human prion disease characterized by adult-onset neurodegenerative manifestations associated with a movement disorder and psychiatric/behavioral disturbances. Patients typically present personality changes, aggressiveness, manias, anxiety and/or depression in conjunction with rapidly progressive cognitive decline (presenting with dysarthria, apraxia, aphasia, and eventually leading to dementia) as well as ataxia (manifesting with gait disturbances, unsteadiness, coordination problems), Parkinsonism, myoclonus, and/or chorea. Additional features may include generalized spasticity, seizures, urine incontinence and pyramidal abnormalities.	Rare genetic neurological disorder
Orphanet:2072	Gaucher disease-ophthalmoplegia-cardiovascular calcification syndrome	GBA	1	Gaucher disease - ophthalmoplegia - cardiovascular calcification is a variant of Gaucher disease, also known as a Gaucher-like disease that is characterized by cardiac involvement.	Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:157954	ANE syndrome	RBM28	1	A rare, genetic, neuro-endocrino-cutaneous disorder characterized by highly variable degrees of alopecia, moderate to severe intellectual disability, progressive, late-onset motor deterioration and combined anterior pituitary hormone deficiency, manifesting with central hypogonadotropic hypogonadism, delayed or absent puberty, growth hormone deficiency (resulting in short stature), progressive central adrenal insufficiency and a hypoplastic anterior pituitary gland. Additional features include hypodontia, flexural reticulate hyperpigmentation, gynecomastia, microcephaly and kyphoscoliosis.	Rare genetic neurological disorder;Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility;Rare genetic skin disease
Orphanet:157962	Oculoauricular syndrome, Schorderet type	HMX1	1	Oculoauricular syndrome, Schorderet type is a rare, genetic developmental defect during embryogenesis syndrome characterized by various ophthalmic anomalies (including congenital microphthalmia, microcornea, cataract, anterior segment dysgenesis, ocular coloboma and early onset rod-cone dystrophy) and abnormal external ears (low-set pinna with crumpled helix, narrow intertragic incisures, abnormal bridge connecting the crus of the helix and the antihelix, narrow external acoustic meatus, and lobule aplasia).	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:2078	Geroderma osteodysplastica	GORAB;PYCR1	2	Geroderma osteodysplastica (GO) is characterized by lax and wrinkled skin (especially on the dorsum of the hands and feet and abdomen), progeroid features, hip dislocation, joint laxity, severe short stature/dwarfism, severe osteoporosis, vertebral abnormalities and spontaneous fractures, and developmental delay and mild intellectual deficit.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic skin disease
Orphanet:157949	Combined immunodeficiency with granulomatosis	RAG1;RAG2	2	A rare, genetic, non-severe combined immunodeficiency disease characterized by immunodeficiency (manifested by recurrent and/or severe bacterial and viral infections), destructive noninfectious granulomas involving skin, mucosa and internal organs, and various autoimmune manifestations (including cytopenias, vitiligo, psoriasis, myasthenia gravis, enteropathy). Immunophenotypically, T-cell and B-cell lymphopenia, hypogammaglobulinemia, abnormal specific antibody production and impaired T-cell function are observed.	Rare genetic skin disease;Rare genetic immune disease
Orphanet:157973	Congenital muscular dystrophy due to LMNA mutation	LMNA	1	Congenital muscular dystrophy due to LMNA mutation is a rare congenital muscular dystrophy characterized by prominent axial hypotonia, dropped head syndrome, predominantly proximal muscle weakness in upper limbs/distal in lower limbs (with absent, poor or lost motor development), joint contractures (initially distal, later proximal), spine rigidity, and early respiratory insufficiency, in the presence of moderately elevated serum creatine kinase. Cardiac arrhythmias and sudden death have been also reported.	Rare genetic neurological disorder;Laminopathy
Orphanet:2084	Glaucoma-ectopia lentis-microspherophakia-stiff joints-short stature syndrome	FBN1	1	Glaucoma-ectopia-microspherophakia-stiff joints-short stature syndrome is characterized by progressive joint stiffness, glaucoma, short stature and lens dislocation. It has been described in three members of a family (the grandfather, his daughter and grandson). It is likely to be transmitted as an autosomal dominant trait. The acronym GEMSS (Glaucoma, Ectopia, Microspherophakia, Stiff joints, Short stature) was proposed as a name for the syndrome. This syndrome shows similarities to Moore-Federman syndrome (see this term).	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:157965	SLC39A13-related spondylodysplastic Ehlers-Danlos syndrome	SLC39A13	1	 gene. Characteristic radiological findings include platyspondyly, osteopenia (predominantly in the vertebrae), widened metaphyses (elbow, wrist, interphalanges), flat epiphyses (femoral neck and short tubular bones), and small broad ilea.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic systemic or rheumatologic disease;Rare genetic bone disease
Orphanet:1826	Frontometaphyseal dysplasia	MAP3K7;FLNA	2	A rare multiple congenital anomalies/dysmorphic syndrome characterized by anomalous ossification and skeletal patterning of the axial and appendicular skeleton, facial dysmorphism and conductive and sensorineural hearing loss.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare genetic bone disease
Orphanet:2050	Cole-Carpenter syndrome	P4HB;SEC24D	2	An extremely rare form of bone dysplasia characterized by the features of osteogenesis imperfecta such as bone fragility associated with multiple fractures, bone deformities (metaphyseal irregularities and bowing of the long bones) and blue sclera, in association with growth failure, craniosynostosis, hydrocephalus, ocular proptosis, and distinctive facial features (e.g. frontal bossing, midface hypoplasia, and micrognathia).	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease
Orphanet:2059	Fryns syndrome	PIGN	1	A rare multiple congenital anomaly syndrome characterized by dysmorphic facial features, congenital diaphragmatic hernia, pulmonary hypoplasia, and distal limb hypoplasia, in addition to variable expression of additional malformations.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:2026	Gingival fibromatosis-hypertrichosis syndrome	ABCA5	1	A rare autosomal dominant disorder characterized by a generalized enlargement of the gingiva occurring at birth or during childhood that is associated with generalized hypertrichosis developing at birth, during the first years of life, or at puberty and predominantly affecting the face, upper limbs, and midback.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:2028	Juvenile hyaline fibromatosis	ANTXR2	1	A rare hyaline fibromatosis syndrome characterized by papulo-nodular skin lesions (especially around the head and neck), soft tissue masses, gingival hypertrophy, joint contractures, and osteolytic bone lesions in variable degrees. Joint contractures may cripple patients and delay normal motor development if occuring in infancy. Severe gingival hyperplasia can interfere with eating and delay dentition. Histopathology analysis of involved tissues reveals cords of spindle-shaped cells embedded in an amorphous, hyaline material.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic skin disease
Orphanet:2021	Fibrochondrogenesis	COL11A1;COL11A2	2	Fibrochondrogenesis is a rare, neonatally lethal, rhizomelic chondrodysplasia. Eleven cases have been reported. The face is distinctive and characterized by protuberant eyes, flat midface, flat small nose with anteverted nares and a small mouth with long upper lip. Cleft palate, micrognathia and bifid tongue can occur. The limbs show marked shortness of all segments with relatively normal hands and feet. No internal anomalies other than omphalocele have been reported. Transmission is probably autosomal recessive. Recurrence in a consanguineous family (affecting both sexes) and concordance of affected male twins have been reported.	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:158796	OBSOLETE: Classic mast cell leukemia	KIT	1	NA	NA
Orphanet:158799	OBSOLETE: Aleukemic mast cell leukemia	KIT	1	NA	NA
Orphanet:2024	Hereditary gingival fibromatosis	GINGF2;SOS1;REST	3	Hereditary gingival fibromatosis (HGF) is a rare benign, slowly progressive, non-inflammatory fibrous hyperplasia of the maxillary and mandibular gingivae that generally occurs with the eruption of the permanent (or more rarely the primary) dentition or even at birth. It presents as a localized or generalized, smooth or nodular overgrowth of the gingival tissues of varying severity. It can be isolated, with autosomal dominant inheritance, or as part of a syndrome.	Rare genetic developmental defect during embryogenesis;Rare genetic odontologic disease
Orphanet:2044	Floating-Harbor syndrome	SRCAP	1	A multiple congenital anomalies/dysmorphic syndrome-intellectual disability that is characterized by facial dysmorphism, short stature with delayed bone age, and expressive language delay.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:2036	Scalp-ear-nipple syndrome	KCTD1	1	A rare syndrome characterised by the following triad: areas of hairless raw skin over the scalp (present at birth and healing during childhood), prominent, hypoplastic ears with almost absent pinnae, and bilateral amastia. Renal and urinary tract abnormalities, as well as cataract, have also been observed.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic eye disease
Orphanet:158769	Plaque-form urticaria pigmentosa	KIT	1	NA	
Orphanet:158766	Typical urticaria pigmentosa	KIT	1	NA	
Orphanet:158687	Lethal acantholytic epidermolysis bullosa	DSP;JUP	2	Lethal acantholytic epidermolysis bullosa is a suprabasal subtype of epidermolysis bullosa simplex (EBS, see this term) characterized by generalized oozing erosions, usually in the absence of blisters.	Rare genetic skin disease
Orphanet:158684	Epidermolysis bullosa simplex with pyloric atresia	PLEC;ITGB4	2	Epidermolysis bullosa simplex with pyloric atresia (EBS-PA) is a basal subtype of epidermolysis bullosa simplex (EBS, see this term) characterized by generalized severe blistering with widespread congenital absence of skin and pyloric atresia.	Rare genetic skin disease
Orphanet:158681	Epidermolysis bullosa simplex with circinate migratory erythema	KRT5	1	Epidermolysis bullosa simplex with circinate migratory erythema (EBS-migr) is a basal subtype of epidermolysis bullosa simplex (EBS, see this term) characterized by belt-like areas of erythema with multiple vesicles and small blisters at the advancing edge of erythema.	Rare genetic skin disease
Orphanet:158676	Dominant dystrophic epidermolysis bullosa, nails only	COL7A1	1	Dystrophic epidermolysis bullosa, nails only is a rare subtype of dystrophic epidermolysis bullosa (DEB, see this term) that shows no blistering and that is characterized by dystrophic or absent nails.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:158673	Acral dystrophic epidermolysis bullosa	COL7A1	1	A very rare dystrophic epidermolysis bullosa (DEB) characterized by blistering confined primarily to the hands and feet.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:158668	Epidermolysis bullosa simplex due to plakophilin deficiency	PKP1	1	Epidermolysis bullosa simplex due to plakophilin deficiency (EBS-PD) is a suprabasal subtype of epidermolysis bullosa simplex (EBS, see this term) characterized by generalized superficial erosions and less commonly blistering.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:158793	OBSOLETE: Lymphoadenopathic mastocytosis with eosinophilia	KIT	1	NA	NA
Orphanet:158778	Isolated bone marrow mastocytosis	KIT	1	NA	
Orphanet:158775	Smoldering systemic mastocytosis	KIT	1	A rare, slowly progressive form of systemic mastocytosis (SM) characterized by gradual accumulation of neoplastic mast cells in the visceral organs. Patients typically present with splenomegaly, hypercellular marrow and, in most cases, urticaria pigmentosa-like skin lesions.	
Orphanet:158772	Nodular urticaria pigmentosa	KIT	1	NA	
Orphanet:1980	Bilateral striopallidodentate calcinosis	PDGFRB;PDGFB;SLC20A2;XPR1	4	Bilateral striopallidodentate calcinosis (BSPDC, also erroneously called Fahr disease) is characterized by the accumulation of calcium deposits in different brain regions, particularly the basal ganglia and dentate nucleus, and is often associated with neurodegeneration.	Rare genetic neurological disorder
Orphanet:1997	Blepharo-cheilo-odontic syndrome	CTNND1;CDH1	2	Blepharo-cheilo-odontic syndrome is an ectodermal dysplasia syndrome characterized by the association of abnormalities of the eyelids, lips, and teeth.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic eye disease
Orphanet:2348	Familial partial lipodystrophy, Dunnigan type	LMNA	1	Familial Partial lipodystrophy, Dunnigan type (FPLD2) is a rare form of genetic lipodystrophy (see this term) characterized by a loss of subcutaneous adipose tissue from the trunk, buttocks and limbs; fat accumulation in the neck, face, axillary and pelvic regions; muscular hypertrophy; and usually associated with metabolic complications such as insulin resistance, diabetes mellitus, dyslipidemia and liver steatosis.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic endocrine disease;Laminopathy
Orphanet:247768	Müllerian aplasia and hyperandrogenism	WNT4	1	NA	Rare genetic gynecological and obstetrical diseases;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease
Orphanet:247790	FTH1-related iron overload	FTH1	1	NA	Rare genetic hepatic disease;Rare inborn errors of metabolism
Orphanet:247798	MUTYH-related attenuated familial adenomatous polyposis	MUTYH	1	NA	Rare genetic gastroenterological disease;Inherited cancer-predisposing syndrome;Rare genetic tumor
Orphanet:247794	Juvenile cataract-microcornea-renal glucosuria syndrome	SLC16A12	1	Juvenile cataract - microcornea - renal glucosuria is an extremely rare autosomal dominant association reported in a single Swiss family and characterized clinically by juvenile cataract associated with bilateral microcornea, and renal glucosuria without other renal tubular defects.	Rare genetic eye disease;Rare inborn errors of metabolism;Rare genetic renal disease
Orphanet:247815	Autosomal recessive ataxia due to PEX10 deficiency	PEX10	1	NA	Rare genetic neurological disorder
Orphanet:2363	Lacrimoauriculodentodigital syndrome	FGF10;FGFR3;FGFR2	3	Lacrimoauriculodentodigital (LADD) syndrome is a multiple congenital anomaly syndrome characterized by hypoplasia, aplasia or atresia of the lacrimal system; anomalies of the ears and hearing loss; hypoplasias, apalsias or atresias of the salivary glands; dental anomalies and digital malformations.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease;Rare genetic skin disease;Genetic otorhinolaryngologic disease
Orphanet:247806	APC-related attenuated familial adenomatous polyposis	APC	1	NA	Rare genetic gastroenterological disease;Inherited cancer-predisposing syndrome;Rare genetic tumor
Orphanet:2340	Keratosis follicularis spinulosa decalvans	MBTPS2;SAT1;LRP1	3	Keratosis follicularis spinulosa decalvans is a rare genodermatosis occurring during infancy or childhood, predominantly affecting males, and characterized by diffuse follicular hyperkeratosis associated with progressive cicatricial alopecia of the scalp, eyebrows and eyelashes. Additional findings can include photophobia, corneal dystrophy, facial erythema, and/or palmoplantar keratoderma.	Rare genetic skin disease
Orphanet:247691	Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations	TREX1	1	Retinal vasculopathy and cerebral leukodystrophy (RVCL) is an inherited group of small vessel diseases comprised of cerebroretinal vasculopathy (CRV), hereditary vascular retinopathy (HRV) and hereditary endotheliopathy with retinopathy, nephropathy and stroke (HERNS; see these terms); all exhibiting progressive visual impairment as well as variable cerebral dysfunction.	Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic systemic or rheumatologic disease
Orphanet:247685	Odontohypophosphatasia	ALPL	1	Odontohypophosphatasia (odonto-HPP) is the least severe form of hypophosphatasia (see this term) characterized by premature exfoliation of primary and/or permanent teeth and/or severe dental caries, in the absence of skeletal system abnormalities.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:247709	Multiple endocrine neoplasia type 2B	RET	1	Multiple endocrine neoplasia 2B (MEN2B) syndrome is a rare aggressive form of MEN2 (see this term) characterized by medullary thyroid carcinoma (MTC, see this term), pheochromocytoma (see this term), mucosal ganglioneuroma, and marfanoid habitus.	Inherited cancer-predisposing syndrome;Rare genetic endocrine disease;Rare genetic tumor
Orphanet:2342	Haim-Munk syndrome	CTSC	1	Haim-Munk syndrome (HMS) is characterized by palmoplantar hyperkeratosis, severe early-onset periodontitis, onychogryposis, pes planus, arachnodactyly and acroosteolysis.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic skin disease
Orphanet:247698	Multiple endocrine neoplasia type 2A	RET	1	Multiple endocrine neoplasia 2A (MEN2A) syndrome is a form of MEN2 (see this term) characterized by medullary thyroid carcinoma (MTC; see this term) in combination with pheochromocytoma (see this term) and primary mild hyperparathyroidism resulting from hyperplasia or adenoma of the parathyroid cells.	Inherited cancer-predisposing syndrome;Rare genetic endocrine disease;Rare genetic tumor
Orphanet:485	Kniest dysplasia	COL2A1	1	Kniest dysplasia is a severe type II collagenopathy characterized by a short trunk and limbs, prominent joints and midface hypoplasia (round face with a flat nasal root).	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:247585	Citrullinemia type II	SLC25A13	1	A severe subtype of citrin deficiency characterized clinically by adult onset (20 and 50 years of age), recurrent episodes of hyperammonemia and associated neuropsychiatric symptoms such as nocturnal delirium, confusion, restlessness, disorientation, drowsiness, memory loss, abnormal behavior (aggression, irritability, and hyperactivity), seizures, and coma.	Rare genetic hepatic disease;Rare inborn errors of metabolism
Orphanet:247598	Neonatal intrahepatic cholestasis due to citrin deficiency	SLC25A13	1	A mild subtype of citrin deficiency characterized clinically by low birth weight, failure to thrive, transient intrahepatic cholestasis, multiple aminoacidemia, galactosemia, hypoproteinemia, hepatomegaly, decreased coagulation factors, hemolytic anemia, variable but mostly mild liver dysfunction, and hypoglycemia.	Rare inborn errors of metabolism
Orphanet:2332	KBG syndrome	ANKRD11	1	KBG syndrome is a rare condition characterised by a typical facial dysmorphism, macrodontia of the upper central incisors, skeletal (mainly costovertebral) anomalies and developmental delay.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:247604	Juvenile primary lateral sclerosis	ALS2;ERLIN2	2	A very rare motor neuron disease characterized by progressive upper motor neuron dysfunction leading to loss of the ability to walk with wheelchair dependence, and subsequently, loss of motor speech production.	Rare genetic neurological disorder
Orphanet:247623	Perinatal lethal hypophosphatasia	ALPL	1	 due to reduced activity of serum alkaline phosphatase (ALP) and causing stillbirth or respiratory failure within days of birth.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:247638	Prenatal benign hypophosphatasia	ALPL	1	A very rare form of hypophosphatasia characterized by prenatal skeletal manifestations (limb shortening and bowing) that slowly resolve spontaneously and later develop into the milder infantile, childhood or adult forms of the disease.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2337	Non-epidermolytic palmoplantar keratoderma	AQP5	1	A rare, isolated, diffuse palmoplantar keratoderma disorder characterized by diffuse, homogeneous, mild to thick, yellowish palmoplantar hyperkeratosis (sometimes spreading over the dorsal aspect of fingers), which presents a white spongy appearance following exposure to water, frequently associated with dermatophyte infections. Hyperhydrosis is usually present and skin biopsy shows non-epidermolytic changes.	Rare genetic skin disease
Orphanet:247651	Infantile hypophosphatasia	ALPL	1	Infantile hypophosphatasia (I-HPP) is a very rare, severe form of hypophosphatasia (see this term) characterized by infantile rickets without elevated serum alkaline phosphatase (ALP) activity and a wide range of clinical manifestations due to hypomineralization.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:247667	Childhood-onset hypophosphatasia	ALPL	1	Childhood-onset hypophosphatasia is a rare, mildform of hypophosphatasia (see this term) characterized by onset after six months of age and widely variable clinical features from low bone mineral density for age, to unexplained fractures,skeletal deformities,and rickets with short stature and waddling gait.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:494	Keratoderma hereditarium mutilans	GJB2	1	Keratoderma hereditarium mutilans is a rare, diffuse, mutilating, hereditary palmoplantar keratoderma disorder characterized by severe, honeycomb-pattern palmoplantar keratosis and pseudoainhum of the digits leading to autoamputation, associated with mild to moderate congenital sensorineural hearing loss. Additional features include stellate keratosis on the extensor surfaces of the fingers, feet, elbows and knees. Alopecia, onychogryphosis, nail dystrophy or clubbing, spastic paraplegia and myopathy may also be associated.	Genetic otorhinolaryngologic disease;Rare genetic skin disease
Orphanet:247676	Adult hypophosphatasia	ALPL	1	A mildform of hypophosphatasia characterized by osteomalacia, chondrocalcinosis, osteoarthropathy, stress fractures duringmiddle age and dental anomalies.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2322	Kabuki syndrome	KMT2D;KDM6A;RAP1A;RAP1B	4	Kabuki syndrome (KS) is a multiple congenital anomaly syndrome characterized by typical facial features, skeletal anomalies, mild to moderate intellectual disability and postnatal growth deficiency.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:247511	Autosomal dominant secondary polycythemia	EPO;EGLN1;EPAS1	3	A rare, genetic, hematologic disease characterized by increased levels of serum hemoglobin, hematocrit and erythrocyte mass, associated with elevated or inappropriately normal erythropoietin serum levels, occurring in various members of a family and with autosomal dominant inheritance.	Rare genetic hematologic disease
Orphanet:247522	Primary ciliary dyskinesia-retinitis pigmentosa syndrome	RPGR	1	Primary ciliary dyskinesia - retinitis pigmentosa is an X-linked ciliary dysfunction of both respiratory epithelium and photoreceptors of the retina leading to ocular disorders (mild night blindness, constriction of the visual field, and scotopic and photopic ERG responses reduced to 30-60%) associated with primary ciliary dyskinesia (see this term) manifestations (chronic bronchorrhea with bronchoectasis and chronic sinusitis) and sensorineural hearing loss.	Rare genetic eye disease
Orphanet:2323	Sanjad-Sakati syndrome	TBCE	1	Sanjad-Sakati syndrome (SSS), also known as hypoparathyroidism - intellectual disability-dysmorphism, is a rare multiple congenital anomaly syndrome, mainly occurring in the Middle East and the Arabian Gulf countries, characterized by intrauterine growth restriction at birth, microcephaly, congenital hypoparathyroidism (that can cause hypocalcemic tetany or seizures in infancy), severe growth retardation, typical facial features (long narrow face, deep-set eyes, beaked nose, floppy and large ears, long philtrum, thin lips and micrognathia), and mild to moderate intellectual deficiency. Ocular findings (i.e. nanophthalmos, retinal vascular tortuosity and corneal opacification/clouding) and superior mesenteric artery syndrome have also been reported. Although SSS shares the same locus with the autosomal recessive form of Kenny-Caffey syndrome (see this term), the latter differs from SSS by its normal intelligence and skeletal features.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease
Orphanet:247546	Acute neonatal citrullinemia type I	ASS1	1	A severe form of citrullinemia type 1 characterized biologically by hyperammonemia and clinically by progressive lethargy, poor feeding and vomiting, seizures and possible loss of consciousness, within one to a few days of birth, with variable signs of increased intracranial pressure. The condition can lead to significant neurologic deficits.	Rare inborn errors of metabolism
Orphanet:247573	Adult-onset citrullinemia type I	ASS1	1	A form of citrullinemia type I characterized clinically by adult onset of symptoms including variable hyperammonemia and less striking neurological findings which may include intense headache, scotomas, migraine-like episodes, ataxia, slurred speech, lethargy and drowsiness. Serious increased intracranial pressure may occur.	Rare inborn errors of metabolism
Orphanet:2407	LOC syndrome	LAMA3	1	LOC syndrome is a subtype of junctional epidermolysis bullosa (JEB, see this term) characterized by an altered cry in the neonatal period and by aberrant production of granulation tissue in particular affecting the upper airway tract, conjunctiva and periungual/subungual sites.	Rare genetic developmental defect during embryogenesis;Rare genetic respiratory disease;Rare genetic skin disease;Rare genetic eye disease
Orphanet:248408	Familial hypodysfibrinogenemia	FGA;FGB;FGG	3	NA	Rare genetic hematologic disease
Orphanet:2396	Encephalocraniocutaneous lipomatosis	FGFR1;KRAS	2	A rare, genetic skin disease characterized by the ocular, cutaneous, and central nervous system anomalies. Typical clinical features include a well-demarcated hairless fatty nevus on the scalp, benign ocular tumors, and central nervous system lipomas, leading sometimes to seizures, spasticity, and intellectual disability. Nevus psiloliparus, focal dermal hypo- or aplasia, eyelid skin tags, colobomas, abnormal intracranial vessels, hemispheric atrophy, porencephalic cyst, and hydrocephalus have also been associated.	Rare genetic tumor;Rare genetic skin disease
Orphanet:248340	Isolated delta-storage pool disease	RUNX1;FLI1	2	Isolated delta-storage pool disease is a rare, isolated, constitutional thrombocytopenia disorder characterized by defective formation and/or malfunction of platelet dense granules, as well as melanosomes in skin cells, resulting in variable manifestations ranging from mild bleeding and easy bruising to moderate mucous/cutaneous hemorrhagic diathesis and bleeding complications after surgery.	Rare genetic hematologic disease
Orphanet:248111	Juvenile Huntington disease	HTT	1	Juvenile Huntington disease (JHD) is a form of Huntington disease (HD; see this term), characterized by onset of signs and symptoms before 20 years of age.	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:2388	Choreoacanthocytosis	VPS13A	1	Chorea-acanthocytosis (ChAc) is a form of neuroacanthocytosis (see this term) and is characterized clinically by a Huntington disease-like phenotype with progressive neurological symptoms including movement disorders, psychiatric manifestations and cognitive disturbances.	Rare genetic neurological disorder;Rare genetic skin disease
Orphanet:2387	Leukonychia totalis	PLCD1	1	Leukonychia totalis is a rare nail anomaly disorder characterized by complete white discoloration of the nails. Patients typically present white, chalky nails as an isolated finding, although other cutaneous or systemic manifestations could also be present.	Rare genetic skin disease
Orphanet:2379	Early-onset parkinsonism-intellectual disability syndrome	RAB39B	1	Early-onset parkinsonism with intellectual deficit is a basal ganglia disorder characterised by parkinsonian-type symptoms (postural changes, tremor, rigidity), megalencephaly and variable intellectual deficit. Other signs are frontal bossing, persistent frontal lobe reflexes, strabismus and seizures. It has been described in three generations of one family. Transmission is X-linked, and the gene is located on chromosomal region Xq27.3-qter.	Rare genetic neurological disorder
Orphanet:247834	Occult macular dystrophy	RP1L1	1	Occult macular dystrophy is a rare, genetic retinal dystrophy disease characterized by bilateral progressive decline of visual acuity, due to retinal dysfunction confined only to the macula, associated with normal fundus and fluorescein angiograms and severly attenuated focal macular and multifocal electroretinograms.	Rare genetic eye disease
Orphanet:247820	Ectodermal dysplasia-syndactyly syndrome	NECTIN4	1	Ectodermal dysplasia-syndactyly syndrome is a rare, genetic ectodermal dysplasia syndrome characterized by sparse to absent scalp hair, eyebrows, and eyelashes (with pili torti when present), widely spaced, conical-shaped teeth with peg-shaped, conical crowns and enamel hypoplasia and palmoplantar hyperkeratosis, associated with partial cutaneous syndactyly in hands and feet.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:2378	Laurin-Sandrow syndrome	LMBR1	1	Laurin-Sandrow syndrome (LSS) is characterised by complete polysyndactyly of the hands, mirror feet and nose anomalies (hypoplasia of the nasal alae and short columella), often associated with ulnar and/or fibular duplication (and sometimes tibial agenesis). It has been described in less than 20 cases. Some cases with the same clinical signs but without nasal defects have also been reported, and may represent the same entity. The etiology of LSS is unknown. Different modes of inheritance have been suggested.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:247868	NLRP12-associated hereditary periodic fever syndrome	NLRP12	1	NLRP12-associated hereditary periodic fever syndrome is a rare autoinflammatory syndrome characterized by episodic and recurrent periods of fever combined with various systemic manifestations such as myalgia, arthralgia, joint swelling, urticaria, headache and skin rash. Common trigger of these episodes is cold.	Rare genetic systemic or rheumatologic disease
Orphanet:2451	Mucocutaneous venous malformations	TEK	1	Mucocutaneous venous malformations (VMCMs) are hereditary vascular malformations characterized by the presence of small, multifocal, bluish-purple venous lesions involving the skin and mucosa.	Rare genetic developmental defect during embryogenesis
Orphanet:244305	Dominant hypophosphatemia with nephrolithiasis or osteoporosis	SLC34A1;SLC9A3R1	2	Dominant hypophosphatemia with nephrolithiasis or osteoporosis is a rare, genetic, renal tubular disease characterized by hypophosphatemia, decreased renal phosphate resorption and hypercalciuria leading to calcium nephrolithiasis and/or nephrocalcinosis and osteoporosis, in the presence of normal/increased serum calcitriol levels.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2440	Isolated split hand-split foot malformation	DLX6;EPS15L1;TP63;SEM1;WNT10B;DLX5;BTRC	7	Split hand-split foot malformation (SHFM) refers to a spectrum of genetically and clinically heterogenous terminal limb defect (see this term) characterized by hypoplasia/ absence of central rays of the hands and feet (that can occur in one to all four digits), median clefts of the hands and/ or feet, aplasia and syndactyly, with a wide range of severity ranging from malformed central finger/ toe to a lobster claw-like appearance of the hands and feet. SHFM can be an isolated malformation or can be a feature in various syndromes (ADULT syndrome, EEC syndrome; see these terms). SHFM usually follows an autosomal dominant pattern of inheritance with incomplete penetrance, but autosomal recessive and rarely X-linked inheritance have also been reported.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:244283	Biliary atresia with splenic malformation syndrome	CFC1	1	Biliary atresia with splenic malformation syndrome (BASM) designates the association of biliary atresia (see this term) and splenic abnormalities (mainly polysplenia and less frequently asplenia, double spleen). Cardiac defect, situs inversus and a preduodenal portal vein can also be present. It represents the embryonal or syndromic form of biliary atresia. It affects newborns or infants and is characterized by jaundice, pale stools, dark urine, failure to thrive, hepatomegaly, coagulopathy, anemia and often palpable spleen.	Rare genetic developmental defect during embryogenesis
Orphanet:244310	RFT1-CDG	RFT1	1	 (3p21.1).	Rare genetic hepatic disease;Rare inborn errors of metabolism;Rare genetic neurological disorder;Genetic otorhinolaryngologic disease;Rare genetic developmental defect during embryogenesis
Orphanet:244242	HELLP syndrome	CD46;CFH;CFI;HELLPAR	4	A rare hemorrhagic disorder due to an acquired platelet anomaly characterized by hemolysis, elevated liver enzymes and thrombocytopenia that affects pregnant or post-partum women, and is frequently associated with severe preeclampsia. Symptoms are variable, typically including right upper quadrant or epigastric abdominal pain, nausea, vomiting, excessive weight gain, generalized edema, hypertension, general malaise, right shoulder pain, backache, and/or headache. Hepatic hemorrhage and rupture, renal failure, and pulmonary edema can result in maternal and/or fetal death.	
Orphanet:296	Ollier disease	PTH1R;IDH2;IDH1	3	Enchondromatosis is a rare primary bone dysplasia disorder characterized by the development of multiple mainly unilateral or asymmetrically distributed enchondromas throughout the metaphyses of the long bones.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic tumor
Orphanet:244275	NA	CFI;CFH	2	NA	NA
Orphanet:2438	Hand-foot-genital syndrome	HOXA13	1	Hand-foot-genital syndrome (HFGS) is a very rare multiple congenital abnormality syndrome characterized by distal limb malformations and urogenital defects.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:243343	Dimethylglycine dehydrogenase deficiency	DMGDH	1	Dimethylglycine dehydrogenase deficiency is an extremely rare autosomal recessive glycine metabolism disorder characterized clinically in the single reported case to date by muscle fatigue and a fish-like odor.	Rare inborn errors of metabolism
Orphanet:243367	Acute fatty liver of pregnancy	HADHA	1	A rare, severe complication occurring in the third trimester of pregnancy or in early postpartum period bearing a risk for perinatal and maternal mortality and characterized by jaundice, rise of hepatic injuries and evolving to acute liver failure and encephalopathy.	
Orphanet:247353	Generalized pustular psoriasis	IL36RN;AP1S3	2	Generalized pustular psoriasis is a severe inflammatory skin disease that can be life-threatening and that is characterized by recurrent episodes of high fever, fatigue, episodic erythematous cutaneous eruptions with sterile cutaneous pustules formation on various parts of the body, and neutrophil leukocytosis.	Rare genetic skin disease
Orphanet:247262	Hyperphosphatasia-intellectual disability syndrome	PIGV;PIGL;PIGO;PGAP2;PGAP3;PIGW;PIGY	7	A rare, congenital disorder of glycosylation-related bone disorder characterized by hypotonia, severe developmental delay, intellectual disability, seizures, increased serum alkaline phosphatase, short distal phalanges with hypoplastic nails, and dysmorphic facial features. In some cases, cleft palate, megacolon, anorectal malformations, and congenital heart defects have been reported.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare inborn errors of metabolism
Orphanet:2484	Melnick-Needles syndrome	FLNA	1	Melnick-Needles syndrome (MNS) belongs to the otopalatodigital syndrome spectrum disorder and is associated with a short stature, facial dysmorphism, osseous abnormalities involving the majority of the axial and appendicular skeleton resulting in impaired speech and masticatory problems.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic bone disease
Orphanet:247198	Progressive cerebello-cerebral atrophy	SEPSECS;VPS53	2	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:2473	McKusick-Kaufman syndrome	MKKS	1	McKusick-Kaufman syndrome is a very rare, genetic developmental disorder presenting in the neonatal period characterized by genitourinary malformations, polydactyly, and more rarely, congenital heart disease or gastrointestinal malformations.	Rare genetic developmental defect during embryogenesis;Ciliopathy
Orphanet:2470	Matthew-Wood syndrome	STRA6;RARB	2	Matthew-Wood syndrome is a rare clinical entity including as main characteristics anophthalmia or severe microphthalmia, and pulmonary hypoplasia or aplasia.	Rare genetic developmental defect during embryogenesis;Rare genetic respiratory disease;Rare genetic eye disease
Orphanet:561	Marshall-Smith syndrome	NFIX	1	Marshall-Smith syndrome is a rare genetic disease characterized by tall stature and advanced bone age at birth.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:559	Marinesco-Sjögren syndrome	SIL1;INPP5K	2	Marinesco-Sjögren syndrome (MSS) belongs to the group of autosomal recessive cerebellar ataxias. Cardinal features of MSS are cerebellar ataxia, congenital cataract, and delayed psychomotor development.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:2462	Shprintzen-Goldberg syndrome	SKI;FBN1	2	Shprintzen-Goldberg syndrome (SGS) is a very rare genetic disorder characterized by craniosynostosis, craniofacial and skeletal abnormalities, marfanoid habitus, cardiac anomalies, neurological abnormalities, and intellectual disability.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic systemic or rheumatologic disease;Rare genetic bone disease
Orphanet:2461	Marden-Walker syndrome	PIEZO2	1	Marden-Walker syndrome (MWS) is a malformation syndrome characterized by multiple joint contractures (arthrogryposis), a mask-like face with blepharophimosis, micrognathia, high-arched or cleft palate, low-set ears, decreased muscular bulk, kyphoscoliosis and arachnodactyly.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:251630	Anaplastic oligodendroglioma	IDH2;POT1	2	A rare glial tumor characterized by a grade III oligodendroglial tumour with focal or diffuse anaplastic features. It typically occurs in the supratentorial white matter. Histologically, the cells are enlarged and epithelioid with pleomorphic and increased size nuclei, a vesicular chromatin pattern and prominent nucleoli. Most patients present with seizures.	
Orphanet:251636	NA	RELA;C11ORF95	2	NA	NA
Orphanet:2176	Infantile systemic hyalinosis	ANTXR2	1	Infantile systemic hyalinosis (ISH) is a very rare disorder belonging to the heterogeneous group of genetic fibromatoses and is characterized by progressive joint contractures, skin abnormalities, severe chronic pain and widespread deposition of hyaline material in many tissues such as the skin, skeletal muscle, cardiac muscle, gastrointestinal tract, lymph nodes, spleen, thyroid, and adrenal glands.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:251656	Oligoastrocytoma	IDH2	1	Oligoastrocytoma is a type of low-grade glioma with a mixed astrocytoma and oligodendroglioma histology, manifesting with headaches, speech and motor problems, seizures and, in some, subarachnoid haemorrhage.	
Orphanet:251663	Anaplastic oligoastrocytoma	IDH2	1	A rare and aggressive glial tumor of the central nervous system, that usually presents in adults with seizures, is most often located in the cerebral hemispheres and that is associated with a very poor prognosis.	
Orphanet:2189	Hydrolethalus	HYLS1;KIF7	2	Hydrolethalus (HLS) is a severe fetal malformation syndrome characterized by craniofacial dysmorphic features, central nervous system, cardiac, respiratory tract and limb abnormalities.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:251671	Angiocentric glioma	MYB;QKI	2	An extremely rare slow-growing glial neoplasm of the central nervous system, usually arising in a superficial location in the cerebrum, affecting all ages and both sexes, and characterized by intractable seizures and headaches, with most cases being cured by surgical incision alone and therefore having a good prognosis.	
Orphanet:2190	OBSOLETE: Congenital hydronephrosis	TBX18	1	NA	NA
Orphanet:312	Autosomal dominant epidermolytic ichthyosis	KRT1;KRT10	2	Epidermolytic ichthyosis (EI) is a rare keratinopathic ichthyosis (KPI; see this term), that is characterized by a blistering phenotype at birth which progressively becomes hyperkeratotic.	Rare genetic skin disease
Orphanet:2196	Familial primary hypomagnesemia with hypercalciuria and nephrocalcinosis with severe ocular involvement	CLDN19	1	Familial primary hypomagnesemia with hypercalciuria and nephrocalcinosis with severe ocular involvement (FHHNCOI) is a form of familial primary hypomagnesemia (FPH, see this term), characterized by excessive magnesium and calcium renal wasting, bilateral nephrocalcinosis, progressive renal failure and severe ocular abnormalities.	Rare genetic eye disease;Rare genetic renal disease;Rare inborn errors of metabolism
Orphanet:251576	Gliosarcoma	NFKBIA;MGMT;EGFR;FGFR1;FGFR3;TP53;TACC3;TACC1;PPARG;LZTR1;SEPT14;IDH1	12	NA	
Orphanet:251579	Giant cell glioblastoma	PPARG;NFKBIA;MGMT;EGFR;FGFR1;FGFR3;TP53;TACC3;TACC1;IDH1;LZTR1;SEPT14	12	NA	
Orphanet:251589	Anaplastic astrocytoma	IDH2	1	A rare, high-grade, malignant glial tumor, histologically characterized by abundance of pleomorphic astrocytes and multiple mitotic figures, often associated with diffuse infiltration of the surrounding tissue, considerable edema and mass effect and involvement of the contralateral brain. Depending on the primary localization of the tumor, patients can present with signs of raised intracranial pressure (headache, vomiting, papilledema), seizures, progressive neurological deficits, and/or behavioral changes. The tumor is most commonly localized in the frontal and temporal lobes, brain stem and spinal cord.	
Orphanet:251598	Protoplasmic astrocytoma	IDH2	1	NA	
Orphanet:251604	Gemistocytic astrocytoma	IDH2	1	NA	
Orphanet:251601	Fibrillary astrocytoma	IDH2	1	NA	
Orphanet:251615	Pilomyxoid astrocytoma	BRAF;BRAF;KRAS;RAF1;FGFR1;SRGAP3;NTRK2;KIAA1549	8	NA	
Orphanet:251627	Oligodendroglioma	IDH2;POT1	2	A rare glial tumor characterized by a highly cellular lesion that is diffusly infiltrating at the periphery and consists of evenly-spaced monomorphic cells with the oligodendroglial phenotype. It typically occurs in the supratentorial white matter. Histologically, the cells are uniformly round to oval with round nuclei, delicate chromatin and small nucleoli. Most patients present with seizures.	
Orphanet:2169	Methylcobalamin deficiency type cblE	MTRR	1	NA	Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic hematologic disease
Orphanet:2228	Hypodontia-dysplasia of nails syndrome	MSX1	1	Hypodontia-nail dysplasia syndrome is a form of ectodermal dysplasia.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:2224	Hypertryptophanemia	TDO2	1	Familial hypertryptophanemia is characterized by intellectual deficit associated with behavioral problems: periodic mood swings, exaggerated affective responses and abnormal sexual behavior. Twelve cases have been reported so far. Congenital abnormalities in tryptophan metabolism appear to be responsible for the tryptophanemia and tryptophanuria.	Rare inborn errors of metabolism
Orphanet:2229	Dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome	LMNA	1	This syndrome is characterized by the association of dilated cardiomyopathy and hypergonadotropic hypogonadism (DCM-HH).	Rare genetic cardiac disease;Laminopathy;Rare genetic endocrine disease;Genetic infertility
Orphanet:2237	Hypoparathyroidism-sensorineural deafness-renal disease syndrome	GATA3	1	Hypoparathyroidism-sensorineural deafness-renal disease syndrome is a rare, clinically heterogeneous genetic disorder characterized by the triad of hypoparathyroidism (H), sensorineural deafness (D) and renal disease (R).	Genetic otorhinolaryngologic disease;Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Rare chromosomal anomaly;Rare genetic endocrine disease
Orphanet:2199	Epidermolytic palmoplantar keratoderma	KRT1;KRT9;KRT16	3	NA	Rare genetic skin disease
Orphanet:251863	Desmoplastic/nodular medulloblastoma	SUFU	1	Desmoplastic/nodular medulloblastoma is a histological variant of medulloblastoma (see this term), an embryonic malignancy, often located in one of the cerebellar hemispheres, occurring most frequently in adults and manifesting with symptoms such as vomiting and headache.	
Orphanet:251858	Medulloblastoma with extensive nodularity	SUFU	1	Medulloblastoma with extensive nodularity (MBEN) is a histological variant of medulloblastoma (see this term), an embryonic malignancy, most often located in the inferior medullary velum and then growing into the fourth ventricle, and presenting in infants and young children with symptoms of increased intracranial pressure such as headache, listlessness, vomiting, diplopia and papilledema. It is often associated with Gorlin syndrome (see this term) and has a relatively good prognosis.	
Orphanet:2198	Palmoplantar keratoderma-esophageal carcinoma syndrome	RHBDF2	1	NA	Rare genetic gastroenterological disease;Rare genetic skin disease
Orphanet:2202	Palmoplantar keratoderma-deafness syndrome	GJB2;MT-TS1	2	Palmoplantar keratoderma-deafness syndrome is a keratinization disorder characterized by focal or diffuse palmoplantar keratoderma. A patchy distribution is observed with accentuation on the thenars, hypothenars and the arches of the feet. The disease becomes apparent in infancy and is associated with sensorineural hearing loss that shows a variable age of onset. Due to genetic and clinical similarities, it has been proposed that palmoplantar keratoderma-deafness syndrome, knuckle pads-leukonychia-sensorineural deafness-palmoplantar hyperkeratosis syndrome and keratoderma hereditarium mutilans may represent variants of one broad disorder of syndromic deafness with heterogeneous phenotype. The disease is transmitted in an autosomal dominant manner with incomplete penetrance.	Genetic otorhinolaryngologic disease;Rare genetic skin disease
Orphanet:251899	Choroid plexus carcinoma	TP53	1	Choroid plexus carcinoma is a rare and highly aggressive malignant type of choroid plexus tumor (see this term) occurring almost exclusively in children, presenting with cerebrospinal fluid obstruction in the lateral ventricles (most common), the fourth and third ventricles or in multiple ventricles, leading to hydrocephalus and increased intracranial pressure, and manifesting with nausea, vomiting, abnormal eye movements, gait impairment, seizures and enlarged head circumference.	
Orphanet:251019	2q32q33 microdeletion syndrome	SATB2	1	2q32q33 microdeletion syndrome is a recently described syndrome characterized by a variable phenotype involving moderate to severe intellectual deficit, significant speech delay, persistent feeding difficulties, growth retardation and dysmorphic features.	Rare chromosomal anomaly
Orphanet:251028	2q33.1 microdeletion syndrome	SATB2	1	2q33.1 microdeletion syndrome is a rare chromosomal anomaly syndrome, resulting from the partial deletion of the long arm of chromosome 2, with a highly variable phenotype typically characterized by severe intellectual disability, moderate to severe developmental delay (particularly speech), feeding difficulties, failure to thrive, hypotonia, thin, sparse hair, various dental abnormalities and cleft/high-arched palate. Typical dysmorphic features inlcude high, prominent forehead, down-slanting palpebral fissures and prominent nasal bridge with beaked nose. Various behavioral problems (e.g. hyperactivity, chaotic/repetitive behavior, touch avoidance) are also associated.	Rare chromosomal anomaly
Orphanet:672	Pallister-Hall syndrome	GLI3	1	Pallister-Hall syndrome (PHS), a pleiotropic autosomal dominant malformative disorder, is characterized by hypothalamic hamartoma, pituitary dysfunction, bifid epiglottis, polydactyly, and, more rarely, renal abnormalities and genitourinary malformations.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Ciliopathy;Rare genetic bone disease;Rare genetic endocrine disease
Orphanet:455	Superficial epidermolytic ichthyosis	KRT2	1	Superficial epidermolytic ichthyosis (SEI) is a rare keratinopathic ichthyosis (KI; see this term) characterized by the presence of superficial blisters and erosions at birth.	Rare genetic skin disease
Orphanet:251061	7q31 microdeletion syndrome	FOXP2	1	7q31 microdeletion syndrome is a rare chromosomal anomaly characterized by speech and language disorder, predominantly presenting as an apraxia of speech, sometimes associated with oral motor dyspraxia, dysarthria, receptive and expressive language disorder, and hearing loss. Individuals with larger deletions in this region have also been reported to display intellectual disability and autism.	Rare chromosomal anomaly
Orphanet:251066	8p11.2 deletion syndrome	ANK1	1	8p11.2 deletion syndrome is a contiguous gene syndrome characterized by the association of congenital spherocytosis, dysmorphic features, growth delay and hypogonadotropic hypogonadism.	Rare chromosomal anomaly
Orphanet:251071	8p23.1 microdeletion syndrome	GATA4	1	8p23.1 deletion involves a partial deletion of the short arm of chromosome 8 characterized by low birth weight, postnatal growth deficiency, mild intellectual deficit, hyperactivity, craniofacial abnormalities, and congenital heart defects.	Rare genetic urogenital disease;Rare chromosomal anomaly
Orphanet:2273	Ichthyosis follicularis-alopecia-photophobia syndrome	MBTPS2	1	Ichthyosis follicularis - alopecia - photophobia (IFAP) is a rare genetic disorder characterized by the triad of ichthyosis follicularis, alopecia, and photophobia from birth.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:139	CHILD syndrome	NSDHL	1	CHILD syndrome (Congenital Hemidysplasia with Ichthyosiform nevus and Limb Defects, CS) is an X-linked dominant genodermatosis characterized by unilateral inflammatory and scaling skin lesions with ipsilateral visceral and limb anomalies.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare inborn errors of metabolism;Rare genetic skin disease
Orphanet:457	Harlequin ichthyosis	ABCA12	1	Harlequin ichthyosis (HI) is the most severe variant of autosomal recessive congenital ichthyosis (ARCI; see this term). It is characterized at birth by the presence of large, thick, plate-like scales over the whole body associated with severe ectropion, eclabium, and flattened ears, that later develops into a severe scaling erythroderma.	Rare genetic skin disease;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:251056	6q25 microdeletion syndrome	ARID1B	1	6q25 microdeletion syndrome is a recently described syndrome characterized by developmental delay, facial dysmorphism and hearing loss.	Rare chromosomal anomaly
Orphanet:2239	Familial isolated hypoparathyroidism due to agenesis of parathyroid gland	GCM2	1	X-linked recessive hypoparathyroidism (XLHPT) is a very rare cause of hypoparathyroidism. It has been reported in two multigeneration families from Missouri. Affected males suffer from true neonatal idiopathic hypoparathyroidism leading to severe hypocalcemia with undetectable parathyroid hormone levels and epilepsy. They are also sterile. Carrier females are normocalcemic and asymptomatic. XLHPT is caused by congenital parathyroid gland agenesis. The XLHPT locus has been mapped to chromosome Xq26-q27, in a 1.5 Mb interval flanked by markers F9 and DXS984. Neonatal onset and parathyroid agenesis found at autopsy in one of the patients suggest that the gene involved in XLHPT plays a role in parathyroid gland development.	Rare genetic eye disease;Rare genetic endocrine disease
Orphanet:2241	Megacystis-microcolon-intestinal hypoperistalsis syndrome	LMOD1;MYH11;ACTG2;MYLK	4	Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a rare congenital disease characterized by massive abdominal distension caused by a largely dilated non-obstructed urinary bladder (megacystis), microcolon and decreased or absent intestinal peristalsis.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Rare genetic gastroenterological disease
Orphanet:250984	Autosomal recessive Stickler syndrome	COL11A1;COL9A1;COL9A2;COL9A3	4	 gene, and like other dominantly inherited forms of the disease manifesting with opthalmological (myopia, retinal detachment and cataracts), orofacial (micrognathia, midface hypoplasia and cleft palate) auditory (sensorineural hearing loss) and articular (epiphyseal dysplasia) symptoms	Genetic otorhinolaryngologic disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease
Orphanet:250977	AICA-ribosiduria	ATIC	1	An extremely severe inborn error of purine biosynthesis characterized clinically in the single reported case to date by profound intellectual deficit, epilepsy, dysmorphic features of the knees, elbows, and shoulders and congenital blindness.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:2250	Hyposmia-nasal and ocular hypoplasia-hypogonadotropic hypogonadism syndrome	SMCHD1	1	This syndrome is characterized by the association of severe nasal hypoplasia, hypoplasia of the eyes, hyposmia, hypogeusia and hypogonadotropic hypogonadism.	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility;Rare genetic eye disease
Orphanet:250923	Isolated aniridia	PAX6;TRIM44;FOXC1	3	Isolated aniridia is a congenital bilateral ocular malformation characterized by the complete or partial absence of the iris.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:250972	Polymicrogyria with optic nerve hypoplasia	TUBA8	1	Polymicrogyria with optic nerve hypoplasia is a rare genetic syndrome with central nervous system malformations characterized by severe developmental delay, neonatal hypotonia, seizures, optic nerve hypoplasia and distinct central nervous system malformations including extensive bilateral polymicrogyria, dysplastic or absent corpus callosum and malformed brainstem with loss of demarcation of the pontomedullary junction.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:2255	Pancreatic hypoplasia-diabetes-congenital heart disease syndrome	GATA6	1	Pancreatic hypoplasia-diabetes-congenital heart disease syndrome is characterized by partial pancreatic agenesis, diabetes mellitus, and heart anomalies (including transposition of the great vessels, ventricular or atrial septal defects, pulmonary stenosis, or patent ductus arteriosis).	Rare genetic endocrine disease
Orphanet:251380	Hereditary persistence of fetal hemoglobin-sickle cell disease syndrome	HBB;BCL11A;HBG1;HBG2;KLF1	5	A rare, genetic, hemoglobinopathy characterized by generally mild clinical phenotype, high fetal hemoglobin levels and mild microcytosis and hypochromia. In some cases, acute sickle cell disease manifestations were reported, namely acute chest syndrome and acute pain crisis.	Rare genetic hematologic disease
Orphanet:251383	CK syndrome	NSDHL	1	CK syndrome is a rare, genetic, X-linked syndromic intellectual disability disorder characterized by mild to severe intellectual disability, infancy-onset seizures, post-natal microcephaly, cerebral cortical malformations, dysmorphic facial features (including long, narrow face, almond-shaped palpebral fissures, epicanthic folds, high nasal bridge, malar flattening, posteriorly rotated ears, high arched palate, crowded teeth, micrognathia) and thin body habitus. Long and slim fingers/toes, strabismus, hypotonia, spasticity, optic disc atrophy, and behavioral problems (aggression, attention deficit hyperactivity disorder and irritability) are additional features.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:251370	Sickle cell-hemoglobin D disease syndrome	HBB	1	A rare, genetic hemoglobinopathy characterized by anemia and erythrocyte abnormalities including anisocytosis, poikilocytosis, target cells, and irreversibly sickled cells. Clinical course is similar to sickle cell disease, including acute episodes of pain, splenic infarction and splenic sequestration crisis, vaso-occlusive crisis, acute chest syndrome, ischemic brain injury, osteomyelitis and avascular bone necrosis.	Rare genetic hematologic disease
Orphanet:251375	Sickle cell-hemoglobin E disease syndrome	HBB	1	A rare, genetic hemoglobinopathy usually characterized by mild hemolysis without vaso-occlusive complications or abnormality of red blood cell morphology. However, more severe manifestations have also been reported, including hematuria, splenic infarction, acute chest syndrome, acute episodes of pain and reversible bone marrow necrosis.	Rare genetic hematologic disease
Orphanet:251359	Sickle cell-beta-thalassemia disease syndrome	HBB	1	A rare, genetic hemoglobinopathy that affects red blood cells both in the production of abnormal hemoglobin, as well as the decreased synthesis of beta globin chains. Clinical manifestations depend on the amount of residual beta globin chains production, and are similar to sickle cell disease, including anemia, vascular occlusion and its complications, acute episodes of pain, acute chest syndrome, pulmonary hypertension, sepsis, ischemic brain injury, splenic sequestration crisis and splenomegaly.	Rare genetic hematologic disease
Orphanet:251365	Sickle cell-hemoglobin C disease syndrome	HBB	1	A rare, genetic hemoglobinopathy characterized by anemia, reticulocytosis and erythrocyte abnormalities including target cells, irreversibly sickled cells and crystal-containing cells. Clinical course is similar to sickle cell disease, but less severe and with less complications. Signs and symptoms may include acute episodes of pain, splenic infarction and splenic sequestration crisis, acute chest syndrome, focal segmental glomerulosclerosis, ischemic brain injury, peripheral retinopathy, and osteonecrosis.	Rare genetic hematologic disease
Orphanet:251523	Hyperzincemia and hypercalprotectinemia	PSTPIP1	1	A rare inborn error of zinc metabolism characterized by recurrent infections, hepatosplenomegaly, anemia (unresponsive to iron supplementation) and chronic systemic inflammation in the presence of high plasma concentrations of zinc and calprotectin. Patients typically present dermal ulcers or other cutaneous manifestations (e.g. inflammation) and arthralgia. Severe epistaxis and spontaneous hematomas have also been reported.	Rare inborn errors of metabolism;Rare genetic skin disease
Orphanet:2315	Johanson-Blizzard syndrome	UBR1	1	Johanson-Blizzard syndrome (JBS) is a multiple congenital anomaly characterized by exocrine pancreatic insufficiency, hypoplasia/aplasia of the nasal alae, hypodontia, sensorineural hearing loss, growth retardation, anal and urogenital malformations, and variable intellectual disability.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic endocrine disease
Orphanet:251510	46,XY partial gonadal dysgenesis	WT1;DMRT3;SOX9;SRY;WWOX;ZFPM2;GATA4;NR0B1;NR5A1;MAP3K1;VAMP7	11	46,XY partial gonadal dysgenesis (46,XY PGD) is a disorder of sex development (DSD) associated with anomalies in gonadal development that results in genital ambiguity of variable degree ranging from almost female phenotype to almost male phenotype in a patient carrying a male 46,XY karyotype.	Genetic infertility;Rare genetic gynecological and obstetrical diseases;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease
Orphanet:251393	Localized junctional epidermolysis bullosa, non-Herlitz type	COL17A1;ITGB4	2	Junctional epidermolysis bullosa, localized non-Herlitz-type is a form of non-Herlitz junctional epidermolysis bullosa (JEB-nH, see this term) characterized by localized blistering, and dystrophic or absent nails.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:2309	Pachyonychia congenita	KRT16;KRT17;KRT6A;KRT6B	4	Pachyonychia congenita (PC) is a rare genodermatosis predominantly featuring painful palmoplantar keratoderma, thickened nails, cysts and whitish oral mucosa.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:2307	IVIC syndrome	SALL4	1	IVIC syndrome is a very rare genetic malformation syndrome characterized by upper limb anomalies (radial ray defects, carpal bone fusion), extraocular motor disturbances, and congenital bilateral non-progressive mixed hearing loss.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:251295	Pigmented paravenous retinochoroidal atrophy	CRB1	1	Pigmented paravenous retinochoroidal atrophy (PPRCA) is a rare, commonly bilateral and symmetric retinal disease characterized by non-progressive or slowly progressive chorioretinal atrophy, peripapillary pigmentary changes and accumulation of ''bone-corpuscle'' pigmentation along the retinal veins and which is usually asymptomatic or can present with mild blurred vision.	Rare genetic eye disease
Orphanet:251290	Parietal foramina with clavicular hypoplasia	MSX2	1	A rare genetic bone development disorder characterized by parietal foramina in association with hypoplasia of the clavicles (short abnormal clavicles with tapering lateral ends, with or without loss of the acromion). Additional features may include mild craniofacial dysmorphism (macrocephaly, broad forehead and frontal bossing). No dental abnormalities were reported.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:251282	Autosomal dominant spastic ataxia type 1	VAMP1	1	A rare, genetic, autosomal dominant spastic ataxia disorder characterized by lower-limb spasticity and ataxia in the form of head jerks, ocular movement abnormalities, dysarthria, dysphagia and gait disturbances.	Rare genetic neurological disorder
Orphanet:251279	Microphthalmia-retinitis pigmentosa-foveoschisis-optic disc drusen syndrome	MFRP	1	Microphthalmia-retinitis pigmentosa-foveoschisis-optic disc drusen syndrome is a rare, genetic, non-syndromic developmental defect of the eye disorder characterized by the association of posterior microphthalmia, retinal dystrophy compatible with retinitis pigmentosa, localized foveal schisis and optic disc drusen. Patients present high hyperopia, usually adult-onset progressive nyctalopia and reduced visual acuity, and, on occasion, acute-angle glaucoma.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:251274	Familial hyperaldosteronism type III	KCNJ5	1	Familial hyperaldosteronism type III (FH-III) is a rare heritable form of primary aldosteronism (PA) that is characterized by early-onset severe hypertension, non glucocorticoid-remediable hyperaldosteronism, overproduction of 18-oxocortisol and 18-hydroxycortisol, and profound hypokalemia.	Rare genetic endocrine disease
Orphanet:251262	Familial osteochondritis dissecans	ACAN	1	Familial osteochondritis dissecans is a rare genetic skeletal disorder characterized clinically by abnormal chondro-skeletal development, disproportionate short stature and skeletal deformation mainly affecting the knees, hips, ankles and elbows with onset generally in late childhood or adolescence.	Rare genetic bone disease
Orphanet:251347	Ataxia-telangiectasia-like disorder	MRE11	1	NA	Inherited cancer-predisposing syndrome;Rare genetic neurological disorder
Orphanet:2290	Microvillus inclusion disease	MYO5B;STX3	2	Microvillus inclusion disease (MVID) is a very rare and severe intestinal disease characterized by intractable neonatal secretory diarrhea persisting at bowel rest and specific histological features of the intestinal epithelium.	Rare genetic gastroenterological disease
Orphanet:254857	Lethal infantile mitochondrial myopathy	MT-TT	1	Lethal infantile mitochondrial myopathy is a rare mitochondrial oxidative phosphorylation disorder characterized by progressive generalized hypotonia, progressive external ophthalmoplegia and severe lactic acidosis, which results in early fatality (days to months after birth). Patients may present with lethargy and areflexia and may associate additional features, such as cardiomyopathy, renal dysfunction, liver involvement and seizures.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:254864	Mitochondrial myopathy with reversible cytochrome C oxidase deficiency	TRMU;MT-TE	2	A rare, genetic, mitochondrial oxidative phosphorylation disorder characterized by a potentially life-threatening, severe myopathy manifesting in the neonatal to early infantile period, followed by marked, spontaneous improvement of muscular function by early childhood. Associated biochemical findings include lactic acidosis and a transient, marked decrease in respiratory chain activity.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:2671	Neu-Laxova syndrome	PHGDH;PSAT1	2	Neu-Laxova syndrome (NLS) is a rare, multiple malformation syndrome characterised by severe intrauterine growth retardation (IUGR), severe microcephaly with a sloping forehead, severe ichthyosis (collodion baby type), and facial dysmorphism.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic skin disease;Rare genetic eye disease
Orphanet:1475	Renal coloboma syndrome	PAX2	1	A genetic condition characterized by optic nerve dysplasia and renal hypodysplasia.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:2670	Pierson syndrome	LAMB2	1	A rare syndrome characterised by the association of congenital nephrotic syndrome and ocular anomalies with microcoria.	Rare genetic renal disease;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:254930	Combined oxidative phosphorylation defect type 7	C12ORF65	1	Combined oxidative phosphorylation defect type 7 is a rare mitochondrial disease due to a defect in mitochondrial protein synthesis characterized by a variable phenotype that includes onset in infancy or early childhood of failure to thrive and psychomotor regression (after initial normal development), as well as ocular manifestations (such as ptosis, nystagmus, optic atrophy, ophthalmoplegia and reduced vision). Additional manifestations include bulbar paresis with facial weakness, hypotonia, difficulty chewing, dysphagia, mild dysarthria, ataxia, global muscle atrophy, and areflexia. It has a relatively slow disease progression with patients often living into the third decade of life.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:2697	Arthrogryposis-renal dysfunction-cholestasis syndrome	VPS33B;VIPAS39	2	A rare, multisystem disorder, characterized by neurogenic arthrogryposis multiplex congenita, renal tubular dysfunction and neonatal cholestasis with low serum gamma-glutamyl transferase activity.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic hepatic disease;Rare genetic skin disease
Orphanet:254925	Combined oxidative phosphorylation defect type 4	TUFM	1	Combined oxidative phosphorylation defect type 4 is a rare mitochondrial disorder due to a defect in mitochondrial protein synthesis characterized by a neonatal onset of severe metabolic acidosis and respiratory distress, persistent lactic acidosis with episodes of metabolic crises, developmental regression, microcephaly, abnormal gaze fixation and pursuit, axial hypotonia with limb spasticity and reduced spontaneous movements. Neuroimaging studies reveal polymicrogyria, white matter abnormalities and multiple cystic brain lesions, including basal ganglia, and cerebral atrophy. Decreased activity of complex I and IV have been determined in muscle biopsy.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:254920	Combined oxidative phosphorylation defect type 2	MRPS16	1	Combined oxidative phosphorylation defect type 2 is a rare mitochondrial disorder due to a defect in mitochondrial protein synthesis characterized by severe intrauterine growth retardation, neonatal limb edema and redundant skin on the neck (hydrops), developmental brain defects (corpus callosum agenesis, ventriculomegaly), brachydactyly, dysmorphic facial features with low set ears, severe intractable neonatal lactic acidosis with lethargy, hypotonia, absent spontaneous movements and fatal outcome. Markedly decreased activity of complex I, II + III and IV in muscle and liver have been determined.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:254913	Isolated ATP synthase deficiency	MT-ATP6;MT-ATP8;ATPAF2;ATP5F1E;ATP5F1A;ATPAF1;ATP5F1D	7	Isolated ATP synthase deficiency is a rare, genetic, mitochondrial oxidative phosphorylation disorder that may present with a wide range of symptoms (including muscular hypotonia, hypertrophic cardiomyopathy, psychomotor delay, encephalopathy, peripheral neuropathy, lactic acidosis, 3-methylglutaconic aciduria) and clinical syndromes (including NARP and MILS).	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:255182	Pyruvate dehydrogenase E3-binding protein deficiency	PDHX	1	Pyruvate dehydrogenase E3-binding protein deficiency is a rare mild form of pyruvate dehydrogenase deficiency (PDHD, see this term) characterized by variable lactic acidosis and neurological dysfunction.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:2701	Noonan syndrome-like disorder with loose anagen hair	PPP1CB;SHOC2	2	Noonan-like syndrome with loose anagen hair (NS/LAH) is a Noonan-related syndrome, characterized by facial anomalies suggestive of Noonan syndrome (see this term); a distinctive hair anomaly described as loose anagen hair syndrome (see this term); frequent congenital heart defects; distinctive skin features with darkly pigmented skin, keratosis pilaris, eczema or occasional neonatal ichtyosis (see this term); and short stature, often associated with a GH deficiency and psychomotor delays.	Rare genetic cardiac disease;Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic eye disease;RASopathy
Orphanet:255138	Pyruvate dehydrogenase E1-beta deficiency	PDHB	1	Pyruvate dehydrogenase E1-beta deficiency is an extremely rare form of pyruvate dehydrogenase deficiency (PDHD, see this term) characterized by severe lactic acidosis, developmental delay and hypotonia.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:2698	Knuckle pads-leukonychia-sensorineural deafness-palmoplantar hyperkeratosis syndrome	GJB2	1	A rare, syndromic genetic deafness disease characterized by symmetric or asymmetirc knuckle pads (typically located on the distal and interphalangeal joints), leukonychia, diffuse palmoplantar keratoderma, and congenital, mild to moderate sensorineural deafness.	Genetic otorhinolaryngologic disease;Rare genetic skin disease
Orphanet:255132	Adult-onset autosomal recessive sideroblastic anemia	GLRX5	1	) described in a single patient with adult onset microcytic hypochromic anemia with liver iron overload and type 2 diabetes.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic hematologic disease
Orphanet:254886	Autosomal recessive progressive external ophthalmoplegia	POLG;TK2	2	A rare genetic, neuro-ophthalmological disease characterized by progressive weakness of the external eye muscles, resulting in bilateral ptosis and diffuse, symmetric ophthalmoparesis. Additional signs may include generalized skeletal muscle weakness, muscle atrophy, sensory axonal neuropathy, ataxia, cardiomyopathy, and psychiatric symptoms. It is usually more severe than autosomal dominant form.	Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:254881	Spinocerebellar ataxia with epilepsy	POLG	1	Spinocerebellar ataxia with epilepsy is a rare, mitochondrial DNA maintenance syndrome characterized by cerebellar ataxia, sensory peripheral neuropathy, myoclonus, epilepsy, progressive cognitive impairment, late-onset ptosis and external ophthalmoplegia. Liver failure may also occur, most often in association with the use of antiepileptic drug sodium valproate.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:254875	Mitochondrial DNA depletion syndrome, myopathic form	TK2	1	Myopathic mitochondrial DNA (mtDNA) depletion syndrome is one of the main forms of mtDNA depletion syndrome (see this term) that displays a broad phenotypic spectrum but that is most often characterized by hypotonia, proximal muscle weakness, facial and bulbar weakness and failure to thrive.	Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic developmental defect during embryogenesis;Rare genetic gastroenterological disease
Orphanet:254905	Isolated cytochrome C oxidase deficiency	COX10;MT-CO1;MT-CO2;MT-CO3;COX6B1;COX14;COX20;COA3;COX8A;PET117;COX5A	11	NA	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:254902	Renal tubulopathy-encephalopathy-liver failure syndrome	BCS1L	1	Renal tubulopathy - encephalopathy - liver failure describes a spectrum of phenotypes with manifestations similar but milder than those seen in GRACILE syndrome (see this term) and that can be associated with encephalopathy and psychiatric disorders.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic hepatic disease
Orphanet:254898	Deafness-encephaloneuropathy-obesity-valvulopathy syndrome	PDSS1	1	Deafness-encephaloneuropathy-obesity-valvulopathy syndrome is a rare mitochondrial disease with marked clinical variability typically characterized by encephalomyopathy, kidney disease (nephrotic syndrome), optic atrophy, early-onset deafness, pancytopenia, obesity, and cardiac disease (valvulopathy). Additionally, macrocephaly, intellectual disability, hyperlactatemia, elevated lactate/pyruvate ratio, insulin-dependent diabetes, livedo reticularis, liver dysfunction and seizures have also been associated.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:254892	Autosomal dominant progressive external ophthalmoplegia	POLG;POLG2;SLC25A4;TWNK;RRM2B	5	A rare genetic, neuro-ophthalmological disease characterized by progressive weakness of the external eye muscles, resulting in bilateral ptosis and diffuse symmetric ophthalmoparesis. Additional signs may include skeletal muscle weakness, cataracts, hearing loss, sensory axonal neuropathy, ataxia, parkinsonism, cardiomyopathy, hypogonadism and depression. It is usually less severe than autosomal recessive form.	Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:2712	Oculofaciocardiodental syndrome	BCOR	1	Oculo-facio-cardio-dental syndrome (OFCD) is a very rare multiple congenital anomaly syndrome characterized by dental radiculomegaly, congenital cataract, facial dismorphism and congenital heart disease.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:2717	Oculotrichoanal syndrome	FREM1	1	Oculotrichoanal syndrome is a form of rare, multiple congenital anomalies/dysmorphic syndrome characterized by a combination of various nose, eye, gastrointestinal and genitourinary abnormalities. Clinical presentation is variable and often includes bifid and broad nasal tip, aberrant anterior hairline, coloboma, cryptophthalmos or unilateral anophthalmia, anal anomalies, and omphalocele. Intelligence and global development is normal.	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:2704	Ochoa syndrome	HPSE2;LRIG2	2	Ochoa syndrome is characterized by the association of severe voiding dysfunction and a characteristic facial expression.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis
Orphanet:255210	Mitochondrial DNA-associated Leigh syndrome	MT-ATP6;MT-ND1;MT-ND2;MT-ND3;MT-ND4;MT-ND5;MT-ND6;MT-TL1;MT-TK;MT-TW;MT-TV	11	Maternally inherited Leigh syndrome is a rare subtype of Leigh syndrome (see this term) characterized clinically by encephalopathy, lactic acidosis, seizures, cardiomyopathy, respiratory disorders and developmental delay, with onset in infancy or early childhood, and resulting from maternally-inherited mutations in mitochondrial DNA.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:255229	Navajo neurohepatopathy	MPV17	1	A rare, life-threatening, mitochondrial DNA depletion syndrome disease characterized by severe, progressive sensorimotor neuropathy associated with corneal ulceration, scarring or anesthesia, acral mutilation, metabolic and immunologic derangement, and hepatopathy (which can manifest with fulminant hepatic failure, a Reye-like syndrome or indolent progression to liver cirrhosis, depending on clinical form involved), present in the Navajo Native American population. Clinical presentation includes failure to thrive, distal limb weakness with reduced sensation, limb contractures with loss of funtion, areflexia, recurrent metabolic acidosis with intercurrent illness, immunologic anomalies manifesting with severe systemic infections, and sexual infantilism.	Rare genetic hepatic disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic gastroenterological disease
Orphanet:2707	Oculocerebrofacial syndrome, Kaufman type	UBE3B	1	. An autosomal recessive mode of inheritance seems most likely.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:255235	Mitochondrial DNA depletion syndrome, encephalomyopathic form with renal tubulopathy	RRM2B	1	NA	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic gastroenterological disease;Rare genetic neurological disorder
Orphanet:2710	Oculodentodigital dysplasia	GJA1	1	Oculodentodigital dysplasia (ODDD) is characterized by craniofacial, neurologic, limb and ocular abnormalities.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic eye disease;Rare genetic bone disease
Orphanet:255241	Leigh syndrome with leukodystrophy	NDUFA13;SDHA;SLC19A3;SURF1;COX15;NDUFAF2;NDUFS1;NDUFS2;NDUFS3;NDUFS4;NDUFS7;NDUFS8;NDUFV1;NDUFV2;PDHA1;NDUFAF5;NDUFAF6;TACO1;FOXRED1;NDUFA2;NDUFA10;NDUFA9;MTFMT;LIPT1;PET100;NDUFA4;ECHS1;NDUFA12	28	NA	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic eye disease;Rare genetic neurological disorder
Orphanet:255249	Leigh syndrome with nephrotic syndrome	COQ2;PDSS2	2	A rare, genetic neurometabolic disease characterized by encephalomyopathy (including developmental delay, nystagmus, progressive ataxia, dystonia, amyotrophy, visual loss, sensorineural deafness, seizures) and bilateral, symmetrical lesions in the basal ganglia or brainstem on imaging, associated with nephrotic syndrome.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic eye disease;Rare genetic neurological disorder
Orphanet:2721	Odonto-onycho-dermal dysplasia	WNT10A	1	Odonto-onycho-dermal dysplasia is a form of ectodermal dysplasia characterised by hyperkeratosis and hyperhidrosis of the palms and soles, atrophic malar patches, hypodontia, conical teeth, onychodysplasia, and dry and sparse hair.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:260305	Autosomal recessive sideroblastic anemia	SLC25A38;HSPA9	2	Congenital autosomal recessive sideroblastic anemia (ARSA) is a non-syndromic, microcytic/hypochromic sideroblastic anemia, present from early infancy and characterized by severe microcytic anemia, which is not pyridoxine responsive, and increased serum ferritin.	Rare genetic hematologic disease
Orphanet:2754	Orofaciodigital syndrome type 6	OFD1;TMEM216;KIF7;CPLANE1;TCTN3;PDE6D;KIAA0753	7	Joubert syndrome with orofaciodigital defect (or oral-facial-digital syndrome type 6, OFD6) is a very rare subtype of Joubert syndrome and related disorders (JSRD, see this term) characterized by the neurological features of JS associated with orofacial anomalies and often polydactyly.	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease
Orphanet:2753	Orofaciodigital syndrome type 4	TCTN3	1	Oral-facial-digital syndrome, type 4 is characterized by lingual hamartoma, postaxial polysyndactyly of hands and feet, and mesomelic shortening of the legs with supinate equinovarus feet.	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2751	Orofaciodigital syndrome type 2	NEK1	1	Oral-facial-digital (OFD) type 2 is characterized by hand and feet deformities, facial deformities, midline cleft of the upper lip and tongue hamartomas.	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2750	Orofaciodigital syndrome type 1	OFD1	1	Oral-facial-digital syndrome type 1 (OFD1) is a rare neurodevelopmental disorder in the ciliopathy group that is lethal in males and characterized by variable anomalies including external malformations (craniofacial and digital), and possible involvement of the central nervous system (CNS) and of viscera (kidneys, pancreas and ovaries) in females.	Genetic otorhinolaryngologic disease;Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare genetic skin disease;Rare genetic bone disease
Orphanet:661	Ondine syndrome	PHOX2B;EDN3;GDNF;MYO1H;BDNF	5	 gene is found in 90% of the patients. Association with a Hirschsprung's disease is observed in 16% of the cases. Despite a high mortality rate and a lifelong dependence to mechanical ventilation, the long-term outcome of CCHS should be ultimately improved by multidisciplinary and coordinated follow-up of the patients.	Rare genetic neurological disorder
Orphanet:254361	Autosomal recessive limb-girdle muscular dystrophy type 2Q	PLEC	1	A form of limb-girdle muscular dystrophy characterized by proximal muscle weakness presenting in early childhood (with occasional falls and difficulties in climbing stairs) and a progressive course resulting in loss of ambulation in early adulthood. Muscle atrophy and multiple contractures have also been reported in rare cases.	Rare genetic neurological disorder
Orphanet:2774	Multicentric carpo-tarsal osteolysis with or without nephropathy	MAFB	1	Idiopathic multicentric osteolysis is a very rare syndrome characterized by progressive loss of bone, usually the capsal and tarsal bones, resulting in deformity and disability, as well as chronic renal failure in many cases. The bone and renal disorders are sometimes associated with intellectual deficit and facial abnormalities.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2770	Nasu-Hakola disease	TREM2;TYROBP	2	Nasu-Hakola disease (NHD), also referred to as polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), is a rare inherited leukodystrophy characterized by progressive presenile dementia associated with recurrent bone fractures due to polycystic osseous lesions of the lower and upper extremities.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:254343	Autosomal recessive spastic ataxia-optic atrophy-dysarthria syndrome	MTPAP	1	A rare, genetic, autosomal recessive spastic ataxia disease characterized by onset in early childhood of spastic paraparesis, cerebellar ataxia, dysarthria and optic atrophy.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:254334	Autosomal recessive intermediate Charcot-Marie-Tooth disease type B	KARS	1	An extremely rare subtype of autosomal recessive intermediate Charcot-Marie-Tooth (CMT) disease characterized by a CMT neuropathy associated with developmental delay, self-abusive behavior, dysmorphic features and vestibular Schwannoma. Motor nerve conduction velocities demonstrate features of both demyelinating and axonal pathology.	Rare genetic neurological disorder
Orphanet:2762	Progressive osseous heteroplasia	GNAS	1	 gene (20q13.2-q13.3), coding for guanine nucleotide-binding proteins. POH can, however, be distinguished clinically by the deep and progressive nature of the heterotopic bone formation.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic skin disease
Orphanet:252206	Melanoma and neural system tumor syndrome	CDKN2A	1	Melanoma and neural system tumor syndrome is an extremely rare tumor association characterized by dual predisposition to melanoma and neural system tumors (typically astrocytoma; see this term).	
Orphanet:2763	Osteocraniostenosis	FAM111A	1	Osteocraniostenosis is a lethal skeletal dysplasia characterized by a cloverleaf skull anomaly, facial dysmorphism, limb shortness, splenic hypo/aplasia and radiological anomalies including thin tubular bones with flared metaphyses and deficient calvarial mineralization.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:252202	Constitutional mismatch repair deficiency syndrome	PMS2;MLH1;MSH2;MSH6	4	Constitutional mismatch repair deficiency syndrome is a rare, inherited cancer-predisposing syndrome characterized by the development of a broad spectrum of malignancies during childhood, including mainly brain, hematological and gastrointestinal cancers, although embryonic and other tumors have also been occasionally reported. Non-neoplastic features, in particular manifestations reminiscent of neurofibromatosis type 1 (e.g., café-au-lait spots, freckling, neurofibromas), as well as premalignant and non-malignant lesions (such as adenomas/polpyps) are frequently present before malignancy development.	Rare genetic immune disease
Orphanet:2792	Otofaciocervical syndrome	EYA1;PAX1	2	Otofaciocervical syndrome is a rare, genetic developmental defect during embryogenesis syndrome characterized by distinct facial features (long triangular face, broad forehead, narrow nose and mandible, high arched palate), prominent, dysmorphic ears (low-set and cup-shaped with large conchae and hypoplastic tragus, antitragus and lobe), long neck, preauricular and/or branchial fistulas and/or cysts, hypoplastic cervical muscles with sloping shoulders and clavicles, winged, low, and laterally-set scapulae, hearing impairment and mild intellectual deficit. Vertebral defects and short stature may also be associated.	Rare genetic developmental defect during embryogenesis
Orphanet:254525	Temple syndrome due to paternal 14q32.2 microdeletion	MEG3;DLK1;RTL1	3	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease;Rare chromosomal anomaly
Orphanet:254528	Kagami-Ogata syndrome due to maternal 14q32.2 microdeletion	RTL1;MEG3;DLK1	3	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:2796	Pachydermoperiostosis	SLCO2A1;HPGD	2	 with prominent pachydermia and minimal-to-absent skeletal changes.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2789	Lateral meningocele syndrome	NOTCH3	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:2788	Osteoporosis-pseudoglioma syndrome	LRP5	1	Osteoporosis pseudoglioma syndrome is a very rare autosomal recessive disorder characterized by congenital or infancy-onset blindness and severe juvenile-onset osteoporosis and spontaneous fractures.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease
Orphanet:2791	Otodental syndrome	FGF3	1	Otodental syndrome is a very rare inherited condition characterized by grossly enlarged canine and molar teeth (globodontia) associated with sensorineural hearing loss.	Rare genetic developmental defect during embryogenesis;Rare chromosomal anomaly
Orphanet:2790	Endosteal hyperostosis, Worth type	LRP5	1	Worth type autosomal dominant osteosclerosis is a sclerozing bone disorder characterized by generalized skeletal densification, particularly of the cranial vault and tubular long bones, which is not associated to an increased risk of fracture.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:1306	Buschke-Ollendorff syndrome	LEMD3	1	Buschke-Ollendorff syndrome (BOS) is a benign disorder characterized by the association of osteopoikilosis lesions (``spotted bones'') in the skeleton and connective tissue nevi in the skin.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2783	Autosomal dominant osteopetrosis type 1	LRP5	1	A rare sclerosing bone disorder characterized by skeletal densification that predominantly involves the cranial vault.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2780	Osteopathia striata-cranial sclerosis syndrome	AMER1	1	Osteopathia striata with cranial sclerosis (OS-CS) is a bone dysplasia characterized by longitudinal striations of the metaphyses of the long bones, sclerosis of the craniofacial bones, macrocephaly, cleft palate and hearing loss.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:667	Autosomal recessive malignant osteopetrosis	CLCN7;TCIRG1;TNFSF11;SNX10	4	Infantile malignant osteopetrosis is a rare congenital disorder of bone resorption characterised by generalised skeletal densification.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease
Orphanet:2805	Partial pancreatic agenesis	PTF1A;PDX1	2	Partial agenesis of the pancreas is characterized by the congenital absence of a critical mass of pancreatic tissue.	Rare genetic developmental defect during embryogenesis
Orphanet:254693	Partial hydatidiform mole	NLRP7;KHDC3L	2	Partial hydatiform mole is a type of hydatiform mole (see this term) characterized by abnormal hyperplastic trophoblasts and hydropic villi due to fertilization of a normal ovocyte by two spermatozoa or one abnormal spermatozoon (allowing for some fetal development), and that manifests with vaginal bleeding accompanied by nausea and frequent vomiting, hyperemesis gravidarum, hyperthyroidism and risk of spontaneous miscarriage.	
Orphanet:2807	Papilloma of choroid plexus	TP53	1	Papilloma of the choroid plexus is a rare benign type of choroid plexus tumor (see this term), accounting for 1% of all brain tumors, often occurring in the fourth ventricle (in adults) and the lateral ventricle (in children) but sometimes arising ectopically in the brain parenchyma, and presenting with nausea, vomiting, papilledema, abnormal eye movements, as well as enlarged head circumference, seizures and gait impairment due to an increase in intracranial pressure.	
Orphanet:678	Papillon-Lefèvre syndrome	CTSC	1	Papillon-Lefèvre syndrome (PLS) is a rare ectodermal dysplasia characterized by palmoplantar keratoderma associated with early-onset periodontitis.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic immune disease
Orphanet:254704	Genetic hyperferritinemia without iron overload	FTL	1	Genetic hyperferritinemia without iron overload is a rare biological anomaly defined as high serum ferritin levels without elevations of transferrin saturation, tissue or serum iron and characterized by an apparently asymptomatic clinical phenotype.	
Orphanet:254534	Kagami-Ogata syndrome due to maternal 14q32.2 hypermethylation	DLK1;MEG3;RTL1	3	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:2802	X-linked sideroblastic anemia and spinocerebellar ataxia	ABCB7	1	X-linked sideroblastic anemia and ataxia (XLSA-A) is a rare syndromic, inherited form of sideroblastic anemia (see this term) characterized by mild to moderate anemia (with hypochromia and microcytosis) and early-onset, non- or slowly progressive spinocerebellar ataxia.	Rare genetic hematologic disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:254531	Temple syndrome due to paternal 14q32.2 hypomethylation	RTL1;MEG3;DLK1	3	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease
Orphanet:254688	Complete hydatidiform mole	NLRP7;KHDC3L	2	Complete hydatidiform mole is a type of hydatiform mole (see this term) characterized by abnormal hyperplastic trophoblasts and hydropic villi due to fertilization of an enucleated ovocyte by one or two haploid spermatozoa that can manifest with vaginal bleeding accompanied by nausea and frequent vomiting, hyperemesis gravidarum, risk of spontaneous miscarriage, hyperthyroidism, and has the potential of developing into choriocarcinoma (see this term).	
Orphanet:2498	Syndactyly type 8	FGF16	1	Syndactyly type 8 is a rare, genetic, non-syndromic, congenital limb malformation characterized by unilateral or bilateral fusion of the fourth and fifth metacarpals with no other associated abnomalities. Patients present shortened fourth and fifth metacarpals with excessive separation between their distal ends, resulting in marked ulnar deviation of the little finger and an inability to bring the fifth finger in parallel with the other fingers.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2499	Metachondromatosis	PTPN11	1	Metachondromatosis (MC) is a rare disorder characterized by the presence of both multiple enchondromas and osteochondroma-like lesions.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2500	Acrogeria	COL3A1	1	A rare premature aging syndrome characterized by atrophy of the skin and subcutaneous tissue involving predominantly the distal parts of the extremities, resulting in prematurely aged appearance of the hand and feet. Another prominent feature is the characteristic facies with hollow cheeks, beaked nose, and owl-like eyes. Additional, non-dermatological manifestations, like bone anomalies have been described in some patients. Mode of inheritance has not been definitively established.	Rare genetic skin disease
Orphanet:2501	Metaphyseal chondrodysplasia, Spahr type	MMP13	1	A rare, genetic, primary bone dysplasia disease characterized by usually moderate, postnatal short stature, progressive genu vara deformity, a waddling gait, and radiological signs of metaphyseal dysplasia (i.e. irregular, sclerotic and widened metaphyses), in the absence of biochemical abnormalities suggestive of rickets disease. Intermittent knee pain, lordosis, and delayed motor development may also occasionally be associated.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2504	Metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome	RUNX2	1	Metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome is characterized by metaphyseal dysplasia associated with short stature and facial dysmorphism (a beaked nose, short philtrum, thin lips, maxillary hypoplasia, dystrophic yellowish teeth) and acral anomalies (short fifth metacarpals and/or short middle phalanges of fingers two and five). It has been described in several members spanning four generations of a French-Canadian family. The syndrome is likely to be transmitted as an autosomal dominant trait.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2505	Multiple benign circumferential skin creases on limbs	MAPRE2;TUBB	2	NA	Rare genetic skin disease
Orphanet:2510	Micro syndrome	RAB3GAP1;RAB3GAP2;RAB18;TBC1D20	4	Micro syndrome is an autosomal recessive disorder caracterised by ocular and neurodevelopmental defects and by microgenitalia. It presents with severe intellectual disability, microcephaly, congenital cataract, microcornea, microphthalmia, agenesis/hypoplasia of the corpus callosum, and hypogenitalism.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:2508	Corpus callosum agenesis-abnormal genitalia syndrome	ARX	1	Corpus callosum agenesis-abnormal genitalia syndrome is a rare, genetic developmental defect during embryogenesis syndrome characterized by agenesis of the corpus callosum, mild to severe neurological manifestations (intellectual disability, developmental delay, epilepsy, dystonia), and urogenital anomalies (hypospadias, cryptorchidism, renal dysplasia, ambiguous genitalia). Additionally, skeletal anomalies (limb contractures, scoliosis), dysmorphic facial features (prominent supraorbital ridges, synophris, large eyes) and optic atrophy have been observed.	Rare genetic urogenital disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:2514	Autosomal dominant primary microcephaly	DPP6	1	A rare, genetic, non-syndromic, developmental defect during embryogenesis malformation syndrome characterized by a congenital, non-progressive, occipitofrontal head circumference that is 2 or more standard deviations below the mean for age, gender and ethnicity which is associated with normal brain architecture and uncomplicated by other abnormalities. Borderline to moderate intellectual disability, as well as early psychomotor delay, may or may not be associated.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:2518	Autosomal recessive chorioretinopathy-microcephaly syndrome	PLK4;TUBGCP6;TUBGCP4	3	A rare neuro-opthalmological disease characterized by severe microcephaly of prenatal onset (with diminutive anterior fontanelle and sutural ridging), growth retardation, global developmental delay and intellectual disability (ranging from mild to profound), dysmorphic features (sloping forehead, micro/retrognathia, prominent ears) and visual impairments (including microphthalmia to anophtalmia, generalized retinopathy or multiple punched-out retinal lesions, retinal folds with retinal detachment, optic nerve hypoplasia, strabismus, nystagmus). Brain MRI may show reduced cortical size, cerebral hemispheres, corpus callosum, pachygyria, symplified gyral folding or normal pattern. Other associated features include epilepsy and neurological deficits.	Rare genetic eye disease
Orphanet:2524	Pontocerebellar hypoplasia type 2	TSEN15;TSEN54;TSEN34;TSEN2;SEPSECS	5	Pontocerebellar hypoplasia type 2 (PCH2) is the most common subtype of pontocerebellar hypoplasia (see this term) characterized by neonatal onset and a lack of voluntary motor development and later progressive microencephaly, generalized clonus, development of chorea and spasticity. The majority of patients will not reach puberty.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:2526	Microcephaly-lymphedema-chorioretinopathy syndrome	KIF11	1	Microcephaly with or without chorioretinopathy, lymphedema or intellectual disability (MCLID) is a rare autosomal dominant condition characterized by variable expression of microcephaly, ocular disorders including chorioretinopathy, congenital lymphedema of the lower limbs, and mild to moderate intellectual disability.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic neurological disorder
Orphanet:2554	Ear-patella-short stature syndrome	ORC4;ORC6;CDT1;CDC6;ORC1;GMNN;CDC45	7	Ear-patella-short stature syndrome is an association of malformations including bilateral microtia (severe hypoplasia of ear pinnae), absent patellae, short stature, poor weight gain, and characteristic facial features such as high forehead, micrognathism with full lips and small mouth, and accentuated nasolabial folds (smile wrinkles linking the nostrils to the labial commissure).	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic neurological disorder
Orphanet:2556	Microphthalmia with linear skin defects syndrome	HCCS;COX7B;NDUFB11	3	MIDAS syndrome (Microphthalmia, Dermal Aplasia, and Sclerocornea), also called microphthalmia with linear skin defects syndrome, is characterized by ocular defects (microphthalmia, orbital cysts, corneal opacities) and linear skin dysplasia of the neck, head, and chin. It has been reported in less than 50 patients. Additional findings may include agenesis of corpus callosum, sclerocornea, chorioretinal abnormalities, hydrocephalus, seizures, intellectual deficit, and nail dystrophy. It is transmitted as an X-linked dominant trait with male lethality.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic skin disease
Orphanet:575	Muckle-Wells syndrome	NLRP3	1	Muckle-Wells syndrome (MWS) is an intermediate form of cryopyrin-associated periodic syndrome (CAPS; see this term) and is characterized by recurrent fever (with malaise and chills), recurrent urticaria-like skin rash, sensorineural deafness, general signs of inflammation (eye redness, headaches, arthralgia/myalgia) and potentially life-threatening secondary amyloidosis (AA type).	Rare genetic systemic or rheumatologic disease;Rare genetic immune disease
Orphanet:2573	Moyamoya disease	ACTA2;RNF213	2	Moyamoya disease (MMD) is a rare intracranial arteriopathy involving progressive stenosis of the cerebral vasculature located at the base of the brain causing transient ischemic attacks or strokes.	
Orphanet:2570	Lethal intrauterine growth restriction-cortical malformation-congenital contractures syndrome	GPKOW	1	Holoprosencephaly-hypokinesia syndrome is an extremely rare and fatal central nervous system malformation occurring during embryogenesis, presenting prenatally with holoprosencephaly and fetal hypokinesia as major features. Other manifestations include microcephaly, multiple contractures and intrauterine growth restriction. There have been no further descriptions in the literature since 1988.	Rare genetic developmental defect during embryogenesis
Orphanet:2585	Ataxia-pancytopenia syndrome	SAMD9L	1	A rare genetic disease characterized by cerebellar ataxia, cytopenias and predisposition to bone marrow failure and myeloid leukaemia. Neurologic features variably include slowly progressive cerebellar ataxia or balance impairment with cerebellar atrophy and periventricular white matter T2 hyperintensities in brain MRI, horizontal and vertical nystagmus, dysmetria, dysarthria, pyramidal tract signs and reduced nerve conduction velocity. Hematological abnormalities are variable and may be intermittent and include cytopenias of all cell lineages, immunodeficiency, myelodysplasia and acute myeloid leukemia.	Rare genetic neurological disorder
Orphanet:261144	14q12 microdeletion syndrome	FOXG1	1	14q12 microdeletion syndrome is a recently described syndrome characterized by severe intellectual deficit, with a normal neonatal period, followed by a phase of regression at the age of 3-6 months.	Rare chromosomal anomaly
Orphanet:2576	Mulibrey nanism	TRIM37	1	A rare developmental defect during embryogenesis characterized by growth delay and multiorgan manifestations.	Rare genetic developmental defect during embryogenesis
Orphanet:1359	Carney complex	PRKAR1A	1	Carney complex (CNC) is characterized by spotty skin pigmentation, endocrine overactivity and myxomas.	Rare genetic skin disease;Rare genetic endocrine disease;Rare genetic tumor
Orphanet:261222	Distal 16p11.2 microdeletion syndrome	SH2B1	1	Distal 16p11.2 microdeletion syndrome is a rare chromosomal anomaly syndrome resulting from the partial deletion of the short arm of chromosome 16 with a highly variable phenotype typically characterized by developmental delay, mild intellectual disability and autism spectrum disorder. Macrocephaly (apparent by 2 years of age), structural brain malformations, epilepsy, vertebral anomalies and obesity are frequently associated.	Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease;Rare chromosomal anomaly
Orphanet:2593	Tubular aggregate myopathy	ORAI1;STIM1;CASQ1	3	NA	Rare genetic neurological disorder
Orphanet:261229	14q11.2 microduplication syndrome	FOXG1	1	14q11.2 microduplication syndrome is a rare chromosomal anomaly characterized by developmental delay, mild to severe intellectual disability with speech impairment and epilepsy. Additionally, it may include dysmorphic features (such as hypo- or hypertelorism, dysplastic ears, short palpebral fissures), microcephaly or macrocephaly, behavioral abnormalities, stereotyped hand movements, ataxia, hypotonia, cleft palate.	Rare chromosomal anomaly
Orphanet:2590	Spinal muscular atrophy-progressive myoclonic epilepsy syndrome	ASAH1	1	Spinal muscular atrophy-progressive myoclonic epilepsy syndrome is characterized by hereditary myoclonus and progressive distal muscular atrophy. Less than 10 cases have been reported. Treatment with clonazepam results in complete and lasting improvement of the myoclonus.	Rare genetic neurological disorder
Orphanet:2588	Myhre syndrome	SMAD4	1	Myhre syndrome is characterised by striking muscular build, short stature, reduced joint mobility, brachydactyly, mixed hearing loss and mental retardation of variable severity. Facial dysmorphism with short palpebral fissures, short philtrum, thin lips, maxillary hypoplasia and prognathism is present. Thick skin has been observed in six patients.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:261190	15q14 microdeletion syndrome	MEIS2	1	15q14 microdeletion syndrome is a recently described syndrome characterized by developmental delay, short stature and facial dysmorphism.	Rare chromosomal anomaly
Orphanet:261197	Proximal 16p11.2 microdeletion syndrome	SH2B1	1	The proximal 16p11.2 microdeletion syndrome is a chromosomal anomaly characterized by developmental and language delays, mild intellectual disability, social impairments (autism spectrum disorders), mild variable dysmorphism and predisposition to obesity.	Rare chromosomal anomaly
Orphanet:261295	20p12.3 microdeletion syndrome	BMP2	1	20p12.3 microdeletion syndrome is a recently described syndrome characterized by Wolff-Parkinson-White syndrome (see this term), variable developmental delay and facial dysmorphism.	Rare chromosomal anomaly
Orphanet:261279	17q23.1q23.2 microdeletion syndrome	TBX4	1	17q23.1q23.2 microdeletion syndrome is a recently described syndrome characterized by developmental delay, microcephaly, short stature, heart defects and limb abnormalities.	Rare chromosomal anomaly
Orphanet:261265	17q12 microdeletion syndrome	HNF1B;LHX1	2	17q12 microdeletion syndrome is a rare chromosomal anomaly syndrome resulting from the partial deletion of the long arm of chromosome 17 characterized by renal cystic disease, maturity onset diabetes of the young type 5, and neurodevelopmental disorders, such as cognitive impairment, developmental delay (particularly of speech), autistic traits and autism spectrum disorder. Müllerian aplasia in females, macrocephaly, mild facial dysmorphism (high forehead, deep set eyes and chubby cheeks) and transient hypercalcaemia have also been reported.	Rare chromosomal anomaly
Orphanet:261250	16q24.3 microdeletion syndrome	ANKRD11	1	16q24.3 microdeletion syndrome is a recently described syndrome associated with variable developmental delay, facial dysmorphism, seizures and autistic spectrum disorder.	Rare chromosomal anomaly
Orphanet:2616	3M syndrome	CUL7;OBSL1;CCDC8	3	A primordial growth disorder characterized by low birth weight, reduced birth length, severe postnatal growth restriction, a spectrum of minor anomalies (including facial dysmorphism) and normal intelligence.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2613	Nail-patella-like renal disease	LMX1B	1	A severe nephropathy characterised by renal dysfunction, proteinuria, oedema and microscopic haematuria. It has been described in three brothers, two of which died from end-stage renal insufficiency.	Rare genetic renal disease
Orphanet:261257	Distal 17p13.3 microdeletion syndrome	YWHAE	1	Distal 17p13.3 microdeletion syndrome is a rare partial monosomy of the short arm of chromosome 17 with a variable phenotype characterized by prenatal and postnatal growth retardation, developmental delay, mild intellectual disability, macrocephaly, mild facial dysmorphisms including prominent forehead, hypertelorism, thick upper and/or lower lip vermillion, and structural abnormalities of the brain variably including white matter abnormalities, prominent Virchow-Robin spaces, Chiari I malformation, corpus callosum hypoplasia, but no lissencephaly.	Rare chromosomal anomaly
Orphanet:2623	Geleophysic dysplasia	FBN1;ADAMTSL2;LTBP3	3	A rare skeletal dysplasia characterized by short stature, prominent abnormalities in hands and feet, and a characteristic facial appearance (described as happy'').	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:261330	Distal 22q11.2 microdeletion syndrome	BCR;MAPK1;CRKL	3	Distal 22q11.2 microdeletion syndrome is a rare chromosomal anomaly syndrome, resulting from the partial deletion of the long arm of chromosome 22, with a highly variable phenotype characterized by prematurity, pre- and post-natal growth retardation, developmental delay (particularly speech), mild intellectual disability, variable cardiac defects, and minor skeletal anomalies (such as clinodactyly). Dysmorphic features include prominent forehead, arched eyebrows, deep set eyes, narrow upslanting palpebral fissures, ear abnormalities, hypoplastic alae nasi, smooth philtrum, down-turned mouth, thin upper lip, retro/micrognatia and pointed chin. For certain very distal deletions, there is a risk of developing malignant rhabdoid tumours.	Rare chromosomal anomaly
Orphanet:2639	Fibular aplasia-complex brachydactyly syndrome	BMPR1B;GDF5	2	).	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2632	Langer mesomelic dysplasia	SHOX	1	A rare disorder characterized by severe disproportionate short stature with mesomelic and rhizomelic shortening of the upper and lower limbs.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:261483	Xq27.3q28 duplication syndrome	FMR1	1	Xq27.3q28 duplication syndrome is a recently described syndrome characterized by short stature, hypogonadism, developmental delay and facial dysmorphism.	Rare chromosomal anomaly
Orphanet:2646	Parastremmatic dwarfism	TRPV4	1	A very rare chondrodysplasia characterized by severe dwarfism, kyphoscoliosis, stiffness of large joints and distortion of lower limbs.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:261579	Blepharophimosis-epicanthus inversus-ptosis due to copy number variations	FOXL2	1	NA	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Genetic infertility
Orphanet:261584	Familial adenomatous polyposis due to 5q22.2 microdeletion	APC	1	NA	Rare genetic gastroenterological disease;Inherited cancer-predisposing syndrome;Rare genetic tumor;Rare chromosomal anomaly
Orphanet:2645	Osteoglosphonic dysplasia	FGFR1	1	A rare disorder characterized by dwarfism, severe craniofacial abnormalities and multiple unerupted teeth.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:261600	Alagille syndrome due to 20p12 microdeletion	JAG1	1	NA	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Inherited cancer-predisposing syndrome;Rare genetic cardiac disease;Rare chromosomal anomaly;Rare genetic eye disease;Rare genetic hepatic disease
Orphanet:261619	Alagille syndrome due to a JAG1 point mutation	JAG1	1	NA	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Inherited cancer-predisposing syndrome;Rare genetic cardiac disease;Rare genetic eye disease;Rare genetic hepatic disease
Orphanet:261537	Mowat-Wilson syndrome due to monosomy 2q22	ZEB2	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare chromosomal anomaly
Orphanet:261552	Mowat-Wilson syndrome due to a ZEB2 point mutation	ZEB2	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:261559	Blepharophimosis-epicanthus inversus-ptosis due to 3q23 rearrangement syndrome	FOXL2	1	NA	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Genetic infertility;Rare chromosomal anomaly
Orphanet:2636	Microcephalic osteodysplastic primordial dwarfism types I and III	RNU4ATAC	1	Rare disorders characterized by intrauterine and postnatal growth retardation, microcephaly, facial dysmorphism, skeletal dysplasia, low-birth weight and brain anomalies. Although they were originally described as two separate entities on the basis of radiological criteria (notably small differences in pelvic and long bone structure), later reports confirmed that the two forms represent different modes of expression of the same syndrome.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease;Rare genetic neurological disorder
Orphanet:261572	Blepharophimosis-epicanthus inversus-ptosis due to a point mutation syndrome	FOXL2	1	NA	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Genetic infertility
Orphanet:2658	Lenz-Majewski hyperostotic dwarfism	PTDSS1	1	An extremely rare syndrome associating dwarfism, characteristic facial appearance, cutis laxa and progressive bone sclerosis.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:261629	Alagille syndrome due to a NOTCH2 point mutation	NOTCH2	1	NA	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Inherited cancer-predisposing syndrome;Rare genetic cardiac disease;Rare genetic eye disease;Rare genetic hepatic disease
Orphanet:261638	Okihiro syndrome due to 20q13 microdeletion	SALL4	1	NA	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare chromosomal anomaly
Orphanet:261647	Okihiro syndrome due to a point mutation	SALL4	1	NA	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:261652	Kleefstra syndrome due to a point mutation	KMT2C;EHMT1	2	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:3057	Monoamine oxidase A deficiency	MAOA	1	Monoamine oxidase-A deficiency is a very rare recessive X-linked biogenic amine metabolism disorder characterized clinically by mild intellectual deficit, impulsive aggressiveness, and sometimes violent behavior and presenting from childhood.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:3047	Blepharophimosis-intellectual disability syndrome, SBBYS type	KAT6B	1	Blepharophimosis-intellectual disability syndrome, SBBYS type is characterised by the association of congenital hypothyroidism, facial dysmorphism (microcephaly, blepharophimosis, a bulbous nose, thin lip, low-set ears and micrognathia), postaxial polydactyly and severe intellectual deficit. Less than 20 cases have been reported so far. Cryptorchidism is present in affected males. Some patients also have cardiac anomalies (interventricular communication), hypotonia and growth delay. Autosomal recessive inheritance has been suggested.	Rare genetic neurological disorder;Rare genetic endocrine disease;Rare genetic developmental defect during embryogenesis
Orphanet:3042	Intellectual disability-cataracts-calcified pinnae-myopathy syndrome	ZBTB20	1	Intellectual disability-cataracts-calcified pinnae-myopathy syndrome is a rare, genetic intellectual disability syndrome characterized by macrocephaly, hypotonia, dysmorphic facial features (wide forehead, ptosis, downslanting palpebral fissures, enlarged and calcified external ears, large jaw), sparse body hair, tall stature, and intellectual disability. Hearing loss, insulin-resistant diabetes, and progressive distal muscle wasting (leading to joint contractures) have also been reported in adulthood. Rare manifestations include behavioral abnormalities (aggression and restlessness), hypothyroidism, cerebral calcification, ataxia, and peripheral neuropathy.	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:263662	Familial multiple meningioma	SMARCB1;SUFU;SMARCE1;MN1;PDGFB	5	Familial multiple meningioma is a rare, benign neoplasm of the central nervous system characterized by the development of multiple or, rarely, solitary meningiomas in two or more blood relatives, without other apparent syndromic manifestations. Depending on the localization, growth rate and size of the tumors, patients can present with subtle, gradually worsening or abrupt and severe neurological compromise or can be completely asymptomatic.	
Orphanet:263548	Peeling skin syndrome type A	FLG2;CHST8	2	Peeling skin syndrome (PSS) type A is a non inflammatory form of generalized PSS (see this term), a type of ichthyosis (see this term), characterized by generalized white scaling and superficial painless peeling of the skin.	Rare genetic skin disease
Orphanet:263553	Peeling skin syndrome type B	CDSN	1	Peeling skin syndrome (PSS) type B, also known as peeling skin disease (PSD), is a rare inflammatory form of ichthyosis (see this term) characterized by superficial patchy peeling of the entire skin with underlying erythroderma, pruritus, and atopy.	Rare genetic skin disease
Orphanet:3032	NPHP3-related Meckel-like syndrome	NPHP3	1	NPHP3-related Meckel-like syndrome is a rare, genetic, syndromic renal malformation characterized by cystic renal dysplasia with or without prenatal oligohydramnios, central nervous system abnormalities (commonly Dandy-Walker malformation), congenital hepatic fibrosis, and absence of polydactyly.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Ciliopathy;Rare genetic neurological disorder;Rare genetic hepatic disease
Orphanet:263534	Acral peeling skin syndrome	CSTA;TGM5	2	A rare peeling skin syndrome characterized by superficial peeling of the skin predominantly affecting the dorsa of the hands and feet.	Rare genetic skin disease
Orphanet:263516	Progressive myoclonic epilepsy type 3	KCTD7	1	A rare, genetic, neuronal ceroid lipofuscinosis disorder characterized by infantile- to early childhood-onset of progressive myoclonic seizures (occasionally accompanied by generalized tonic-clonic seizures) and severe, progressive neurological regression, leading to psychomotor and cognitive decline, cerebellar ataxia, dementia and, frequently, early death. Vision loss may be associated. EEG typically reveals epileptiform activity with predominance in the posterior region and photosensitivity.	Rare genetic eye disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:263524	Acute necrotizing encephalopathy of childhood	CPT2;RANBP2	2	A rare neurologic disease characterized by a rapid onset of seizures, an altered state of consciousness, neurologic decline, and variable degrees of hepatic dysfunction following a respiratory or gastrointesitnal infection (e.g. mycoplasma, influenza virus) in a previously healthy child. Brain MRI of patients reveals bilateral, multiple, symmetrical lesions predominantly observed in thalami and brainstem, but also in periventricular white matter and cerebellum in some cases.	
Orphanet:263501	COG4-CDG	COG4	1	COG4-CDG is an extremely rare form of CDG syndrome (see this term) characterized clinically in the single reported case to date by seizures, some dysmorphic features, axial hyponia, slight peripheral hypertonia and hyperreflexia.	Rare genetic hepatic disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:263508	COG1-CDG	COG1	1	COG1-CDG is an extremely rare form of CDG syndrome (see this term) characterized clinically in the few cases reported to date by variable signs including microcephaly, growth retardation, psychomotor retardation and facial dysmorphism.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic neurological disorder;Rare genetic cardiac disease;Rare inborn errors of metabolism;Genetic otorhinolaryngologic disease
Orphanet:3021	RAPADILINO syndrome	RECQL4	1	A rare syndrome for which the acronym indicates the principal signs: RA for radial ray defect, PA for both patellae hypoplasia or aplasia and cleft or highly arched palate, DI for diarrhea and dislocated joints, LI for little size and limb malformations, NO for long, slender nose and normal intelligence.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:263482	Spondyloepiphyseal dysplasia, Maroteaux type	TRPV4	1	Spondyloepiphyseal dysplasia, Maroteaux type is a very rare type of spondyloepiphyseal dysplasia (see this term) described in fewer than 10 patients to date and characterized clinically by dysplastic epiphyses, short stature appearing in infancy, short neck, short and stubby hands and feet, scoliosis, genu valgum, abnormal pelvis, osteoporosis and osteoarthritis.	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:263494	DPM3-CDG	DPM3	1	DPM3-CDG is an extremely rare form of CDG syndrome (see this term) characterized clinically in the single reported case by muscle weakness, waddling gait and dilated cardiomyopathy (see this term).	Rare inborn errors of metabolism;Rare genetic neurological disorder;Rare genetic cardiac disease
Orphanet:263487	COG5-CDG	COG5	1	COG5-CDG is an extremely rare form of CDG syndrome (see this term) characterized clinically in the single reported case to date by moderate mental retardation with slow and inarticulate speech, truncal ataxia, and mild hypotonia.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:263458	Hyperinsulinism due to INSR deficiency	INSR	1	Hyperinsulinemic hypoglycemia due to INSR deficiency is a very rare autosomal dominant form of familial hyperinsulinism characterized clinically in the single reported family by postprandial hypoglycemia, fasting hyperinsulinemia, and an elevated serum insulin-to-C peptide ratio, and a variable age of onset.	Rare genetic endocrine disease
Orphanet:263455	Hyperinsulinism due to HNF4A deficiency	HNF4A	1	Hyperinsulinism due to HNF4A deficiency is a form of diazoxide-sensitive diffuse hyperinsulinism (DHI), characterized by macrosomia, transient or persistent hyperinsulinemic hypoglycemia (HH), responsiveness to diazoxide and a propensity to develop maturity-onset diabetes of the young subtype 1 (MODY-1; see this term).	Rare genetic endocrine disease;Rare genetic developmental defect during embryogenesis
Orphanet:1832	Lethal osteosclerotic bone dysplasia	FAM20C	1	A rare disorder defined by generalized osteosclerosis with periosteal bone formation, characteristic facial dysmorphism, brain abnormalities including intracerebral calcifications, and neonatal lethal course.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:3019	Ramon syndrome	ELMO2	1	A rare, genetic, primary bone dysplasia syndrome characterized by bilateral, painless swelling of the face extending from the mandible to the inferior orbital margins (cherubism), epilepsy, gingival fibromatosis (possibly obscuring teeth), and intellectual disability. Other associated variable features include hypertrichosis, stunted growth, juvenile rheumatoid arthritis, and development of ocular abnormalities (e.g. pigmentary retinopathy, optic disc pallor, Axenfeld anomaly). Radiological images typically show bilateral multifocal radiolucency involving the body, angle and ramus of the mandible and coronoid process.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:263463	CHST3-related skeletal dysplasia	CHST3	1	CHST3-related skeletal dysplasia is a very rare bone disorder characterized clinically by short stature of prenatal onset; dislocation of the knees, hips or elbows; club feet; limitation of range of motion of large joints; progressive kyphosis; and occasional scoliosis. In a few patients, minor heart valve dysplasia has also been described. Intellect, vision and hearing are normal.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare inborn errors of metabolism
Orphanet:263410	Infantile spasms-psychomotor retardation-progressive brain atrophy-basal ganglia disease syndrome	SLC19A3	1	Infantile spasms-psychomotor retardation-progressive brain atrophy-basal ganglia disease syndrome is a rare, genetic disorder of thiamine metabolism and transport characterized by infantile spasms progressing to symptomatic generalized or partial seizures, severe global developmental delay, progressive brain atrophy, and bilateral thalamic and basal ganglia lesions.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:263417	Bartter syndrome with hypocalcemia	CASR	1	Bartter syndrome with hypocalcemia is a type of Bartter syndrome (see this term) characterized by hypocalcemia, hypomagnesemia and hypoparathyroidism along with features of Henle's loop dysfunction (polyuria, hypokalemic alkalosis, increased levels of plasma renin and aldosterone, low blood pressure and vascular resistance to angiotensin II). Bartter syndrome with hypocalcemia is a very rare manifestation of autosomal dominant hypocalcemia (ADH; see this term)	Rare genetic renal disease;Rare genetic neurological disorder;Rare genetic endocrine disease
Orphanet:769	Rabson-Mendenhall syndrome	INSR	1	A rare syndrome that belongs to the group of extreme insulin-resistance syndromes (which also includes leprechaunism, the lipodystrophies, and the type A and B insulin resistance syndromes).	Rare genetic endocrine disease;Rare genetic skin disease
Orphanet:3005	Pyle disease	SFRP4	1	A rare bone dysplasia characterized by genu valgum, metaphyseal anomalies with broadening of the long bones extending into the diaphyses and giving the femora and tibiae an Erlenmeyer flask'' appearance, widening of the ribs and clavicles, platyspondyly and cortical thinning.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:263347	MRCS syndrome	BEST1	1	MRCS syndrome is a rare, genetic retinal dystrophy disorder characterized by bilateral microcornea, rod-cone dystrophy, cataracts and posterior staphyloma, in the absence of other systemic features. Night blindness is typically the presenting manifestation and nystagmus, strabismus, astigmatism and angle closure glaucoma may be associated findings. Progressive visual acuity deterioration, due to pulverulent-like cataracts, results in poor vision ranging from no light perception to 20/400.	Rare genetic eye disease
Orphanet:2990	Autosomal recessive multiple pterygium syndrome	CHRNG	1	NA	Rare genetic developmental defect during embryogenesis
Orphanet:263297	Glycogen storage disease with severe cardiomyopathy due to glycogenin deficiency	GYG1	1	Glycogen storage disease type 15 is an extremely rare genetic glycogen storage disease reported in one patient to date. Clinical signs included muscle weakness, cardiac arrhythmia associated with accumulation of abnormal storage material in the heart and glycogen depletion in skeletal muscle.	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:3138	Ulnar-mammary syndrome	TBX3	1	Ulnar-mammary syndrome (UMS) is a rare developmental disorder characterized by ulnar defects, mammary and apocrine gland hypoplasia and genital anomalies. Delayed puberty dental anomalies, short stature and obesity have also been described.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:3144	Schneckenbecken dysplasia	SLC35D1;INPPL1	2	Schneckenbecken dysplasia (or chondrodysplasia with snail-like pelvis) is a prenatally lethal spondylodysplastic dysplasia.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare inborn errors of metabolism
Orphanet:798	Schinzel-Giedion syndrome	SETBP1	1	Schinzel-Giedion syndrome (SGS) is an ectodermal dysplasia syndrome chiefly characterized by a distinctive facial dysmorphism, hydronephrosis, severe developmental delay, typical skeletal malformations, and genital and cardiac anomalies.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Inherited cancer-predisposing syndrome;Rare genetic skin disease
Orphanet:3115	Roussy-Lévy syndrome	PMP22;MPZ	2	NA	Rare genetic neurological disorder
Orphanet:3102	Richieri Costa-Pereira syndrome	EIF4A3	1	Richieri Costa-Pereira syndrome is characterized by short stature, Robin sequence, cleft mandible, pre/postaxial hand anomalies (including hypoplastic thumbs), and clubfoot. It has been described in 14 Brazilian families and in one unrelated French patient. Prominent low set ears and a highly arched palate were also observed. Transmission is autosomal recessive.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:3107	Autosomal dominant Robinow syndrome	DVL3;WNT5A;DVL1;FZD2	4	The more common type of Robinow syndrome (RS) characterized by mild to moderate limb shortening and abnormalities of the head, face and external genitalia.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:3086	Autosomal dominant vitreoretinochoroidopathy	BEST1	1	A rare, genetic, vitreous-retinal disease characterized by ocular developmental anomalies such as microcornea, a shallow anterior chamber, glaucoma and cataract. Abnormal chorioretinal pigmentation is present, usually lying between the vortex veins and the ora serrata for 360 degrees.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:3088	Revesz syndrome	TINF2	1	Revesz syndrome is a rare severe phenotypic variant of dyskeratosis congenita (DC; see this term) with an onset in early childhood, characterized by features of DC (e.g. skin hyper/hypopigmentation, nail dystrophy, oral leukoplakia, high risk of bone marrow failure (BMF) and cancer, developmental delay sparse and fine hair) in conjunction with bilateral exudative retinopathy, and intracranial calcifications.	Rare genetic hematologic disease;Rare genetic eye disease
Orphanet:3097	Meacham syndrome	WT1	1	Meacham syndrome is a multiple malformation syndrome characterized by congenital diaphragmatic abnormalities, genital defects and cardiac malformations.	Rare genetic gynecological and obstetrical diseases;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease
Orphanet:3077	X-linked intellectual disability-psychosis-macroorchidism syndrome	MECP2	1	An X-linked syndromic intellectual disability characterized by developmental delay, variable degree of intellectual disability, speech delay or absent speech, pyramidal signs, tremor, macroorchidism and variable mood and behavior problems, including psychosis and autistic-like behavior. Males are predominantly affected, some females show lower cognitive abilities.	Rare genetic neurological disorder
Orphanet:3063	X-linked intellectual disability, Snyder type	SMS	1	X-linked intellectual disability, Snyder type is a rare X-linked intellectual disability syndrome characterized by hypotonia, asthenic build with diminished muscle mass, severe generalized psychomotor delay, unsteady gait and moderate to severe intellectual disability, as well as a long, thin, asymmetrical face with prominent lower lip, long fingers and toes and nasal, dysarthric or absent speech. Bone abnormalities (e.g., osteoporosis, kyphoscoliosis, fractures, joint contractures) are also characteristic. Myoclonic, or myoclonic-like, seizures and renal abnormalities have been associated in some patients.	Rare genetic neurological disorder
Orphanet:2886	TARP syndrome	RBM10	1	TARP syndrome is a rare developmental defect during embryogenesis syndrome characterized by Robin sequence (micrognathia, glossoptosis, and cleft palate), atrial septal defect, persistence of the left superior vena cava, and talipes equinovarus. The phenotype is variable, some patients present with further dysmorphic characteristics (e.g. hypertelorism, ear abnormalities) while others do not have any key findings. Additional features, such as syndactyly, polydactyly, or brain anomalies (e.g. cerebellar hypoplasia), have also been reported. The syndrome is almost invariably lethal with affected males either dying prenatally or living just a few months.	Rare genetic cardiac disease;Rare genetic developmental defect during embryogenesis
Orphanet:2884	Piebaldism	SNAI2;KIT	2	Piebaldism is a rare congenital pigmentation skin disorder characterized by the presence of hypopigmented and depigmented skin areas (leukoderma) on various parts of the body, preferentially on the forehead, chest, abdomen, upper arms, and lower extremities, that are associated with a white forelock (poliosis), and in some cases with hypopigmented and depigmented eyebrows and eyelashes.	Rare genetic skin disease
Orphanet:2879	Phocomelia, Schinzel type	WNT7A	1	Schinzel phocomelia syndrome, also called limb/pelvis hypoplasia/aplasia syndrome, is characterized by skeletal malformations affecting the ulnae, pelvic bones, fibulae and femora. As the phenotype is similar to that described in the malformation syndrome known as Al-Awadi/Raas-Rothschild syndrome, they are thought to be the same disorder.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:268920	Isolated megalencephaly	TBC1D7	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:268882	Arnold-Chiari malformation type I	DKK1	1	A central nervous system malformation characterized by caudal displacement of the cerebellar tonsils exceeding 5mm below the foramen magnum with or without syringomyelia. Symptoms vary in onset and severity and include suboccipital headache, neck pain, vertigo, tinnitus, ocular symptoms (diplopia, blurred vision, photofobia, nystagmus), lower cranial nerve signs, cerebellar ataxia, and spasticity. Some affected individuals can be asymptomatic.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:268770	Upper thoracic spina bifida cystica	MTHFD1;VANGL2;TBXT;VANGL1;FUZ;MTHFR	6	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:268766	Cervicothoracic spina bifida cystica	VANGL1;VANGL2;TBXT;FUZ;MTHFR;MTHFD1	6	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:268762	Cervical spina bifida cystica	VANGL2;FUZ;MTHFR;VANGL1;TBXT;MTHFD1	6	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:268758	Lumbosacral spina bifida cystica	VANGL2;FUZ;MTHFD1;TBXT;MTHFR;VANGL1	6	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:268752	Thoracolumbosacral spina bifida cystica	VANGL2;FUZ;MTHFD1;TBXT;MTHFR;VANGL1	6	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:268748	Total spina bifida cystica	VANGL2;FUZ;MTHFD1;TBXT;MTHFR;VANGL1	6	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:268740	Upper thoracic spina bifida aperta	VANGL2;FUZ;MTHFD1;TBXT;MTHFR;VANGL1	6	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:268823	Occipital encephalocele	DACT1	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:2874	Phakomatosis pigmentokeratotica	HRAS	1	Phakomatosis pigmentokeratotica (PPK) is a very rare epidermal nevus disorder characterized by the association of speckled lentiginous nevi with epidermal sebaceous nevi, and extracutaneous anomalies.	Rare genetic tumor;Rare genetic developmental defect during embryogenesis
Orphanet:2848	Camptodactyly-arthropathy-coxa-vara-pericarditis syndrome	PRG4	1	Camptodactyly-arthropathy-coxa-vara-pericarditis (CACP) syndrome is a rare, genetic, rheumatologic disease characterized by congenital or early-onset camptodactyly and symmetrical, polyarticular, non-inflammatory, large joint arthropathy with synovial hyperplasia, as well as progressive coxa vara deformity and, occasionally, non-inflammatory pericarditis.	
Orphanet:268384	Thoracolumbosacral spina bifida aperta	VANGL2;FUZ;MTHFD1;TBXT;MTHFR;VANGL1	6	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:2855	Perrault syndrome	ERAL1;HSD17B4;TWNK;HARS2;CLPP;LARS2	6	Perrault syndrome (PS) is characterized by the association of ovarian dysgenesis in females with sensorineural hearing impairment. In more recent PS reports, some authors have described neurologic abnormalities, notably progressive cerebellar ataxia and intellectual deficit.	Genetic otorhinolaryngologic disease;Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic urogenital disease
Orphanet:2854	Fuhrmann syndrome	WNT7A	1	Fuhrmann syndrome is mainly characterized by bowing of the femora, aplasia or hypoplasia of the fibulae and poly-, oligo-, and syndactyly.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:268388	Lumbosacral spina bifida aperta	VANGL2;FUZ;MTHFD1;TBXT;MTHFR;VANGL1	6	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:268392	Cervical spina bifida aperta	VANGL2;FUZ;MTHFD1;TBXT;MTHFR;VANGL1	6	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:708	Peters anomaly	FOXC1;CYP1B1;PITX2;PAX6;FOXE3	5	Peters anomaly (PA) is a congenital corneal opacity disorder characterized by a central corneal leukoma that obstructs the pupil leading to visual loss as well as absence of the posterior corneal stroma and Descemet membrane.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:268397	Cervicothoracic spina bifida aperta	VANGL2;FUZ;MTHFD1;TBXT;MTHFR;VANGL1	6	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:2850	Alopecia-intellectual disability syndrome	ITGB6;AHSG	2	An extremely rare genetic syndromic intellectual disability described in less than 20 families to date and characterized by total or partial alopecia associated with intellectual deficit. The syndrome can be associated with other anomalies such as seizures, sensorineural hearing loss, delayed psychomotor development, and/or hypertonia.	Rare genetic neurological disorder;Rare genetic skin disease
Orphanet:268377	Total spina bifida aperta	FUZ;MTHFD1;TBXT;MTHFR;VANGL1;VANGL2	6	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:268114	RAS-associated autoimmune leukoproliferative disease	KRAS;NRAS	2	RAS-associated autoimmune leukoproliferative disease (RALD) is a rare genetic disorder characterized by monocytosis, autoimmune cytopenias, lymphoproliferation, hepatosplenomegaly, and hypergammaglobulinemia.	Rare genetic immune disease;Inherited cancer-predisposing syndrome
Orphanet:268129	Spheroid body myopathy	MYOT	1	Spheroid body myopathy is a rare form of myofibrillar myopathy characterized by predominantly proximal muscle weakness (that could be either non- or slowly progressive), associated with spheroid body inclusions (composed of myofilamentous material within individual muscle fibers) in skeletal muscle biopsy. Presentation is varied and may range from asymptomatic to severe muscle weakness that manifests with absent Achilles reflexes, gait abnormality and/or other motor incapacitations.	Rare genetic neurological disorder
Orphanet:2822	Autosomal recessive spastic paraplegia type 11	SPG11	1	A complex hereditary spastic paraplegia characterized by progressive lower limbs weakness and spasticity, upper limbs weakness, dysarthria, hypomimia, sphincter disturbances, peripheral neuropathy, learning difficulties, cognitive impairment and dementia. Magnetic resonance imaging shows thin corpus callosum, cerebral atrophy, and periventricular white matter changes.	Rare genetic neurological disorder
Orphanet:268261	DYRK1A-related intellectual disability syndrome due to 21q22.13q22.2 microdeletion	DYRK1A	1	A rare, syndromic intellectual disability characterized by global developmental delay including severely delayed or absent speech, moderate to severe intellectual disability, behavioral issues, stereotypic behavior, febrile seizures and epilepsy, abnormal gait, vision defects, and characteristic facial features. Intrauterine growth restriction and feeding difficulties are frequently present.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare chromosomal anomaly
Orphanet:2836	PEHO syndrome	KIF1A;ZNHIT3	2	PEHO (Progressive encephalopathy with Edema, Hypsarrhythmia and Optic atrophy) syndrome is a rare neurodegenerative disorder belonging to the group of infantile progressive encephalopathies.	Rare genetic neurological disorder;Rare genetic skin disease;Rare genetic eye disease
Orphanet:268162	Intermediate maple syrup urine disease	BCKDHA;BCKDHB;DBT;PPM1K	4	Intermediate maple syrup urine disease (intermediate MSUD) is a milder form of MSUD (see this term) characterized by persistently raised branched-chain amino acids (BCAAs) and ketoacids, but fewer or no acute episodes of decompensation.	Rare inborn errors of metabolism
Orphanet:268145	Classic maple syrup urine disease	BCKDHA;BCKDHB;DBT	3	Classic maple syrup urine disease (classic MSUD) is the most severe and probably common form of MSUD (see this term) characterized by a maple syrup odor in the cerumen at birth, poor feeding, lethargy and focal dystonia, followed by progressive encephalopathy and central respiratory failure if untreated.	Rare inborn errors of metabolism
Orphanet:268184	Thiamine-responsive maple syrup urine disease	BCKDHA;BCKDHB;DBT	3	Thiamine-responsive maple syrup urine disease (thiamine-responsive MSUD) is a less severe variant of MSUD (see this term) that manifests with a phenotype similar to intermediate MSUD (see this term) but that responds positively to treatment with thiamine.	Rare inborn errors of metabolism
Orphanet:2833	Stiff skin syndrome	FBN1	1	Stiff skin syndrome is a rare, slowly progressive cutaneous disease characterized by rock-hard skin bound firmly to the underlying tissues (mainly on the shoulders, lower back, buttocks and thighs), mild hypertrichosis and hyperpigmentation overlying the affected areas of skin, as well as limited joint mobility (mainly of large joints) with flexion contractures. Cutaneous nodules, affecting mostly distal interphalangeal joints, as well as extracutaneous manifestations, including diffuse entrapment neuropathy, scoliosis, a tiptoe gait and a narrow thorax, may be associated. Restrictive pulmonary changes, muscle weakness, short stature and growth delay have also been reported. No vascular hyperreactivity, immunologic abnormalities nor visceral, muscular or bone involvement has been described.	Rare genetic skin disease
Orphanet:268173	Intermittent maple syrup urine disease	BCKDHA;BCKDHB;DBT	3	Intermittent maple syrup urine disease (intermittent MSUD) is a mild form of MSUD (see this term) where patients (when well) are asymptomatic with normal levels of branched-chain amino acids (BCAAs) but with catabolic stress are at risk of acute decompensation with ketoacidosis, which can lead to cerebral edema and coma if untreated.	Rare inborn errors of metabolism
Orphanet:2834	Wrinkly skin syndrome	ATP6V0A2	1	Wrinkly skin syndrome (WSS) is characterized by wrinkling of the skin of the dorsum of the hands and feet, an increased number of palmar and plantar creases, wrinkled abdominal skin, multiple skeletal abnormalities (joint laxity and congenital hip dislocation), late closing of the anterior fontanel, microcephaly, pre- and postnatal growth retardation, developmental delay and facial dysmorphism (a broad nasal bridge, downslanting palpebral fissures and hypertelorism).	Rare inborn errors of metabolism;Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic neurological disorder
Orphanet:2969	Proteus-like syndrome	PTEN	1	Proteus-like syndrome describes patients who do not meet the diagnostic criteria for Proteus syndrome (see this term) but who share a multitude of characteristic clinical features of the disease.	Rare genetic tumor;Inherited cancer-predisposing syndrome;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:750	Pseudoachondroplasia	COMP	1	Pseudoachondroplasia is characterized by severe growth deficiency and deformations such as bow legs and hyperlordosis.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:1848	Renal agenesis, bilateral	GREB1L;RET;ITGA8;FGF20	4	Bilateral renal agenesis is the most profound form of renal agenesis (see this term), characterized by complete absence of kidney development, absent ureters and subsequent absence of fetal renal function resulting in Potter sequence with pulmonary hypoplasia related to oligohydramnios, which is fatal shortly after birth.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis
Orphanet:2950	Triphalangeal thumb-polysyndactyly syndrome	SHH;LMBR1	2	Triphalangeal thumb-polysyndactyly syndrome (TPT-PS) is a hand-foot malformation characterized by triphalangeal thumbs and pre- and postaxial polydactyly, isolated syndactyly or complex polysyndactyly.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:740	Hutchinson-Gilford progeria syndrome	ZMPSTE24;LMNA	2	Hutchinson-Gilford progeria syndrome is a rare, fatal, autosomal dominant and premature aging disease, beginning in childhood and characterized by growth reduction, failure to thrive, a typical facial appearance (prominent forehead, protuberant eyes, thin nose with a beaked tip, thin lips, micrognathia and protruding ears) and distinct dermatologic features (generalized alopecia, aged-looking skin, sclerotic and dimpled skin over the abdomen and extremities, prominent cutaneous vasculature, dyspigmentation, nail hypoplasia and loss of subcutaneous fat).	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic skin disease;Laminopathy
Orphanet:2957	Guttmacher syndrome	HOXA13	1	Guttmacher syndrome is an extremely rare syndrome characterized by hypoplastic thumbs and halluces, 5th finger clinobrachydactyly, postaxial polydactyly of the hands, short or uniphalangeal 2nd toes with absent nails and hypospadias.	Rare genetic urogenital disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2924	Isolated polycystic liver disease	PRKCSH;SEC63;LRP5	3	Isolated polycystic liver disease (PCLD) is a genetic disorder characterized by the appearance of numerous cysts spread throughout the liver and that in most cases is described as autosomal dominant polycystic liver disease (ADPCLD).	Rare genetic hepatic disease
Orphanet:2896	Pitt-Hopkins syndrome	TCF4	1	Pitt-Hopkins syndrome (PHS) is characterized by the association of intellectual deficit, characteristic facial dysmorphism and problems of abnormal and irregular breathing.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:2899	Brachyolmia-amelogenesis imperfecta syndrome	LTBP3	1	An exceedingly rare form of brachyolmia, characterized by mild platyspondyly, broad ilia, elongated femoral necks with coxa valga, scoliosis, and short trunked short stature associated with amelogenesis imperfecta of both primary and permanent dentition.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2907	Hereditary acrokeratotic poikiloderma	FERMT1	1	NA	Rare genetic skin disease
Orphanet:264580	Glycogen storage disease due to liver phosphorylase kinase deficiency	PHKA2;PHKG2	2	Glycogen storage disease (GSD) due to liver phosphorylase kinase (PhK) deficiency is a benign inborn error of glycogen metabolism characterized by hepatomegaly, growth retardation, and mild delay in motor development during childhood.	Rare genetic hepatic disease;Rare inborn errors of metabolism
Orphanet:264675	Hereditary pulmonary alveolar proteinosis	CSF2RB;CSF2RA;OAS1	3	Congenital pulmonary alveolar proteinosis is a very rare primary interstitial lung disease due to pulmonary surfactant accumulation within the alveolar macrophages and alveoli, characterized by a variable clinical course ranging from an asymptomatic clinical presentation and spontaneous remission, to symptoms such as dyspnea and cough, or to severe respiratory failure.	Rare genetic respiratory disease;Rare genetic immune disease
Orphanet:2919	Orofaciodigital syndrome type 5	DDX59	1	Oral-facial-digital syndrome, type 5 is characterized by median cleft of the upper lip, postaxial polydactyly of hands and feet, and oral manifestations (duplicated frenulum).	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:3377	Trismus-pseudocamptodactyly syndrome	MYH8	1	A rare, genetic, distal arthrogryposis characterized by pseudocamptodactyly, mild foot deformities, moderately short stature, and short muscles and tendons resulting in a limited range of motion of the hands, legs, and mouth, the later presenting with trismus.	Rare genetic developmental defect during embryogenesis
Orphanet:275777	Heritable pulmonary arterial hypertension	ACVRL1;BMPR2;TBX4;ENG;CAV1;SMAD9;KCNK3;EIF2AK4	8	Heritable pulmonary arterial hypertension (HPAH) is a form of pulmonary arterial hypertension (PAH, see this term), occurring due to mutations in PAH predisposing genes or in a familial context. HPAH is characterized by elevated pulmonary arterial resistance leading to right heart failure. HPAH is progressive and potentially fatal.	
Orphanet:275786	Drug- or toxin-induced pulmonary arterial hypertension	BMPR2	1	Drug- or toxin-induced pulmonary arterial hypertension (PAH) is a form of pulmonary arterial hypertension (PAH, see this term) secondary to the exposition to drugs. Drug- or toxin-induced PAH is characterized by elevated pulmonary arterial resistance leading to right heart failure. Drug or toxin induced PAH is progressive and potentially fatal.	NA
Orphanet:275798	Pulmonary arterial hypertension associated with connective tissue disease	HLA-B	1	Pulmonary arterial hypertension (PAH, see this term) associated with connective tissue disease (PAH-CTD) is a form of pulmonary arterial hypertension (PAH, see this term) characterized by an elevated pulmonary arterial resistance leading to right heart failure observed as a complication of a connective tissue disease.	NA
Orphanet:3363	Trichomegaly-retina pigmentary degeneration-dwarfism syndrome	PNPLA6	1	Trichomegaly-retina pigmentary degeneration-dwarfism syndrome, also known as Oliver-McFarlane syndrome, is an extremely rare genetic disorder characterized by hair abnormalities, severe chorioretinal atrophy, hypopituitarism, short stature, and intellectual disability.	Rare genetic eye disease;Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:3366	Isolated trigonocephaly	FGFR1;FREM1	2	Isolated trigonocephaly is a nonsyndromic form of craniosynostosis characterized by the premature fusion of the metopic suture.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease
Orphanet:276145	Malignant epithelial tumor of salivary glands	PRKD1	1	Malignant epithelial tumor of salivary glands is a rare neoplastic disease characterized by the presence of a tumor located in the parotid, sublingual, submandibular and/or minor salivary glands, which presents with a wide spectrum of clinical features depending on the location, size and type of salivary gland involved, ranging from clinically asymptomatic, slow-growing, painless mass(es), that may or may not be fixed to underlying skin or muscles, to rapidly growing mass(es) associated with pain, facial weakness/nerve palsy, otorrhoea, dysphagia, palatal/parapharyngeal fullness, nasal obstruction/bleeding, voice hoarseness/change, dyspnea, trismus, palate bone erosion, telangiectasia, mucosal/skin ulceration and/or cervical adenopathy.	
Orphanet:3412	VACTERL with hydrocephalus	FANCB	1	VACTERL is an acronym for Vertebral anomalies, Anal atresia, Congenital cardiac disease, Tracheoesophageal fistula, Renal anomalies, and Limb defects. VACTERL associated with hydrocephalus has rarely been reported and is thought to be an autosomal recessive anomaly. The condition is described as a uniformly lethal or developmentally devastating disorder distinct from the VATER association.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:276152	Multiple endocrine neoplasia type 4	CDKN1B	1	Multiple endocrine neoplasia type 4 (MEN4) is a very rare form of MEN (see this term), an inherited cancer syndrome, characterized by parathyroid and anterior pituitary tumors, possibly associated with adrenal, renal, and reproductive organ tumors.	Rare genetic endocrine disease;Rare genetic tumor
Orphanet:276066	Bile acid CoA ligase deficiency and defective amidation	SLC27A5	1	Bile acid CoA ligase deficiency and defective amidation is an anomaly of bile acid synthesis (see this term) characterized by fat malabsorption, neonatal cholestasis and growth failure.	Rare inborn errors of metabolism;Rare genetic hepatic disease
Orphanet:275872	Frontotemporal dementia with motor neuron disease	VCP;TARDBP;FUS;SQSTM1;C9ORF72;TBK1;CHCHD10	7	Frontotemporal dementia with motor neuron disease (FTD-MND) is a type of frontotemporal lobar degeneration characterized by the insidious onset (between the ages of 38-78 years) of dementia-associated psychiatric symptoms (e.g. personality changes, uninhibited behavior, irritability, aggressiveness), memory difficulties, global intellectual impairment, emotional disorders and transcortical motor aphasia that eventually leads to mutism, in addition to the manifestations of motor neuron disease such as neurogenic muscular wasting (similar to what is seen in amyotrophic lateral sclerosis; see this term). The disease is progressive, with death occurring 2-5 years after onset.	Rare genetic neurological disorder
Orphanet:3384	Truncus arteriosus	NKX2-6;PLXND1	2	 truncal valve). Pulmonary arteries originate from the common arterial trunk distal to the coronary arteries and proximal to the first brachiocephalic branch of the aortic arch. TA typically overrides a large outlet ventricular septal defect (VSD). The intracardiac anatomy usually displays situs solitus and atrioventricular (AV) concordance.	Rare genetic cardiac disease
Orphanet:275864	Behavioral variant of frontotemporal dementia	TMEM106B;PSEN1;CHMP2B;TREM2;VCP;MAPT;GRN;SQSTM1;C9ORF72	9	Behavioral variant of frontotemporal dementia (bv-FTD) is a form of frontotemporal dementia (FTD; see this term), characterized by progressive behavioral impairment and a decline in executive function with frontal lobe-predominant atrophy.	Rare genetic neurological disorder
Orphanet:3332	Hypoplastic tibiae-postaxial polydactyly syndrome	SHH;LMBR1	2	Hypoplastic tibia-polydactyly syndrome is a very rare congenital malformation syndrome characterized by bilateral hypoplasia of the tibia with polydactyly of the feet and hands.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:3329	Tibial aplasia-ectrodactyly syndrome	BHLHA9	1	Tibial aplasia-ectrodactyly syndrome is a rare condition characterized by congenital ectrodactylous limb malformations associated with tibial aplasia or hypoplasia.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:3323	Braddock-Carey syndrome	KIF15	1	NA	NA
Orphanet:3322	Hoyeraal-Hreidarsson syndrome	DKC1;TERT;TINF2;RTEL1;ACD;PARN	6	An X-linked syndromic intellectual disability considered to be a severe variant of dyskeratosis congenita characterized by intrauterine growth retardation, microcephaly, cerebellar hypoplasia, progressive combined immune deficiency and aplastic anemia.	Rare genetic neurological disorder;Rare genetic hematologic disease;Rare genetic immune disease;Rare genetic developmental defect during embryogenesis
Orphanet:275555	Preeclampsia	FLT1;STOX1;CORIN	3	Preeclampsia is a hypertensive disorder of pregnancy that is characterized by new-onset hypertension with proteinuria presenting after 20 weeks of gestation, and depending on mild or severe forms may initially present with severe headache, visual disturbances, and hyperreflexia.	
Orphanet:275534	Myostatin-related muscle hypertrophy	MSTN	1	NA	
Orphanet:275517	Autoimmune lymphoproliferative syndrome with recurrent viral infections	CASP8	1	A rare genetic disorder characterized by lymphadenopathy and/or splenomegaly and recurrent infections due to herpes viruses.	Rare genetic immune disease;Inherited cancer-predisposing syndrome
Orphanet:3352	Tricho-dento-osseous syndrome	DLX3	1	Tricho-dento-osseous dysplasia (TDO) belongs to the ectodermal dysplasias and is characterised by curly/kinky hair at birth, enamel hypoplasia with discolouration and molar taurodontism, increased overall bone mineral density (BMD) and increased thickness of the cortical bones of the skull.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:3342	Arterial tortuosity syndrome	SLC2A10	1	A rare autosomal recessive connective tissue disorder characterized by tortuosity and elongation of the large and medium-sized arteries and a propensity towards aneurysm formation, vascular dissection, and stenosis of the pulmonary arteries.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic vascular disease
Orphanet:3339	Toriello-Lacassie-Droste syndrome	KRAS	1	Oculo-ectodermal syndrome (OES) is characterized by the association of epibulbar dermoids and aplasia cutis congenital.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:3338	Toriello-Carey syndrome	DDX3X	1	Toriello Carey syndrome is a multiple congenital anomaly syndrome characterized by craniofacial dysmorphic features, cerebral anomalies, swallowing difficulties, cardiac defects and hypotonia.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:3472	Yunis-Varon syndrome	FIG4;VAC14	2	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:3319	Congenital amegakaryocytic thrombocytopenia	MPL	1	An isolated constitutional thrombocytopenia characterized by an isolated and severe decrease in the number of platelets and megakaryocytes during the first years of life that develops into bone marrow failure with pancytopenia later in childhood.	Rare genetic hematologic disease
Orphanet:3473	Zimmermann-Laband syndrome	ATP6V1B2;KCNH1	2	Zimmermann-Laband syndrome (ZLS) is a rare disorder characterized by gingival fibromatosis, coarse facial appearance, and absence or hypoplasia of nails or terminal phalanges of hands and feet.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:3459	Wilson-Turner syndrome	HDAC8;LAS1L	2	Wilson-Turner syndrome (WTS) is a very rare X-linked multisystem genetic disease characterized by intellectual disability, truncal obesity, gynecomastia, hypogonadism, dysmorphic facial features, and short stature.	Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease;Rare genetic neurological disorder
Orphanet:3460	Torg-Winchester syndrome	MMP2;MMP14	2	NA	NA
Orphanet:3464	Woodhouse-Sakati syndrome	DCAF17	1	Woodhouse-Sakati syndrome is a multisystemic disorder characterized by hypogonadism, alopecia, diabetes mellitus, intellectual deficit and extrapyramidal signs with choreoathetoid movements and dystonia.	Rare genetic neurological disorder;Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility
Orphanet:2995	Baraitser-Winter cerebrofrontofacial syndrome	ACTB;ACTG1	2	Baraitser-Winter syndrome (BWS) is a malformation syndrome, characterized by facial dysmorphism (hypertelorism with ptosis, broad bulbous nose, ridged metopic suture, arched eyebrows, progressive coarsening of the face), ocular coloboma, pachygyria and/or band heterotopias with antero-posterior gradient, progressive joint stiffening, and intellectual deficit of variable severity, often with severe epilepsy. Pachygyria - epilepsy - intellectual disability - dysmorphism (Fryns-Aftimos syndrome (FA); see this term) corresponds to the appearance of BWS in elderly patients.	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic neurological disorder
Orphanet:1827	Acromelic frontonasal dysplasia	ZSWIM6	1	A rare frontonasal dysplasia characterized by distinct craniofacial (large fontanelle, hypertelorism, bifid nasal tip, nasal clefting, brachycephaly, median cleft face, carp-shaped mouth), brain (interhemispheric lipoma, agenesis of the corpus callosum), and limb (tibial hypoplasia/aplasia, club foot, symmetric preaxial polydactyly of the feet and bilateral clubbed and thickened nails of halluces) malformations as well as intellectual disability. Other manifestations sometimes reported include absent olfactory bulbs, hypopituitarism and cryptorchidism.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:268973	Isolated focal cortical dysplasia type Ia	SLC35A2	1	NA	
Orphanet:269008	Isolated focal cortical dysplasia type IIb	TSC2;MTOR;TSC1	3	NA	
Orphanet:269001	Isolated focal cortical dysplasia type IIa	TSC2;MTOR	2	NA	
Orphanet:2460	Van den Ende-Gupta syndrome	SCARF2	1	Van den Ende-Gupta syndrome is a very rare syndrome characterized by blepharophimosis, arachnodactyly, joint contractures, and characteristic dysmorphic features.	Rare genetic developmental defect during embryogenesis
Orphanet:3416	Hyperostosis corticalis generalisata	LRP5;SOST	2	Hyperostosis corticalis generalisata, also known as van Buchem disease, is a rare craniotubular hyperostosis characterized by hyperostosis of the skull, mandible, clavicles, ribs and diaphyses of the long bones, as well as the tubular bones of the hands and feet. Clinical manifestations include increased skull thickness with cranial nerve entrapment causing inconsistent cranial nerve palsies.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:3450	Weissenbacher- Zweymuller syndrome	COL11A2;COL2A1	2	Weissenbacher-Zweymuller syndrome (WZS) is characterized by short stature at birth, neonatal micrognathia, cleft palate, rhizomelic chondrodysplasia with 'dumbbell' shaped arm and leg bones, hypertelorism and vertebral coronal clefts.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:3453	Autoimmune polyendocrinopathy type 1	AIRE	1	A rare, genetic, disease that manifests in childhood or early adolescence with a combination of chronic mucocutaneous candidiasis, hypoparathyroidism and autoimmune adrenal failure.	Rare genetic eye disease;Rare genetic immune disease;Rare genetic endocrine disease;Rare genetic gastroenterological disease
Orphanet:3449	Weill-Marchesani syndrome	ADAMTS10;FBN1;LTBP2	3	Weill-Marchesani syndrome (WMS) is a rare condition characterized by short stature, brachydactyly, joint stiffness, and characteristic eye abnormalities including microspherophakia, ectopia of the lens, severe myopia, and glaucoma.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease
Orphanet:3454	Intellectual disability-developmental delay-contractures syndrome	ZC4H2	1	Intellectual disability-developmental delay-contractures syndrome, formerly known as Wieacker-Wolff syndrome, is a severe X-linked recessive neurodevelopmental disorder characterized by severe contractures (arthrogryposis; see this term) and intellectual disability.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:269510	Congenital non-communicating hydrocephalus	CCDC88C	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:269505	Congenital communicating hydrocephalus	MPDZ	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:269215	Isolated Dandy-Walker malformation without hydrocephalus	ZIC4;ZIC1	2	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:269212	Isolated Dandy-Walker malformation with hydrocephalus	ZIC1;ZIC4	2	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:1856	Spondyloperipheral dysplasia-short ulna syndrome	COL2A1	1	Spondyloperipheral dysplasia-short ulna syndrome is a rare, genetic, primary bone dysplasia, with highly variable phenotype, typically characterized by platyspondyly, brachydactyly type E changes (short metacarpals and metatarsals, short distal phalanges in hands and feet), bilateral short ulnae and mild short stature. Other reported features include additional skeletal findings (e.g. midface hypoplasia, degenerative changes in proximal femora, limited elbow extension, bilateral sacralization of L5, clubfeet), as well as myopia, hearing loss, and intellectual disability.	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:280333	Autosomal recessive limb-girdle muscular dystrophy type 2P	DAG1	1	A form of limb-girdle muscular dystrophy characterized by slowly-progressive, mainly proximal, muscle weakness presenting in early childhood (with difficulties walking and climbing stairs) and mild to severe intellectual disability. Additional manifestations reported include microcephaly, mild increase in thigh or calf muscles, and contractures of the ankles.	Rare genetic neurological disorder
Orphanet:280325	Distal monosomy 12p	ERC1	1	A rare partial autosomal monosomy characterized by language development delay with childhood apraxia of speech, mild intellectual disability, behavourial abnormalities (autistic spectrum disorder, attention deficit hyperactivity disorder, anxiety) and mildly dysmorphic nonspecific features. Additional clinical features may include muscular hypotonia and joint laxity, hernias and microcephaly.	Rare chromosomal anomaly
Orphanet:280293	Pelizaeus-Merzbacher-like disease due to AIMP1 mutation	AIMP1	1	NA	Rare genetic neurological disorder
Orphanet:280288	Pelizaeus-Merzbacher-like disease due to HSPD1 mutation	HSPD1	1	NA	Rare genetic neurological disorder
Orphanet:280365	Autosomal semi-dominant severe lipodystrophic laminopathy	LMNA	1	NA	Rare genetic skin disease;Rare genetic endocrine disease;Laminopathy
Orphanet:3197	Hereditary hyperekplexia	ATAD1;GLRA1;GLRB;GPHN;SLC6A5	5	Hereditary hyperekplexia is a hereditary neurological disorder characterized by excessive startle responses.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:280356	PLIN1-related familial partial lipodystrophy	PLIN1	1	A rare genetic lipodystrophy characterized by loss of subcutaneous adipose tissue primarily affecting the lower limbs and gluteal region due to a defect in the PLIN1 gene. Associated features of insulin resistance, hepatic steatosis, dyslipidemia, hypertension, axillary acanthosis nigricans and muscular hypertrophy of the lower limbs are typical.	Rare genetic skin disease;Rare genetic endocrine disease
Orphanet:3193	Supravalvular aortic stenosis	ELN	1	SupraValvar Aortic Stenosis (SVAS) is characterized by the narrowing of the aorta lumen (close to its origin) or other arteries (branch pulmonary arteries, coronary arteries). This narrowing of the aorta or pulmonary branches may impede blood flow, resulting in heart murmur and ventricular hypertrophy (in case of aorta involvement). The narrowing results from a thickening of the artery wall, which is not related to atherosclerosis.	Rare genetic developmental defect during embryogenesis
Orphanet:280406	Familial steroid-resistant nephrotic syndrome with sensorineural deafness	COQ6	1	Familial steroid-resistant nephrotic syndrome with sensorineural deafness is a rare, genetic coenzyme Q10 deficiency characterized by sensorineural deafness and severe, progressive nephrotic syndrome not responding to steroid treatment. Clinical manifestations include early onset proteinuria, hypoalbuminemia and edema, leading to end-stage renal disease. The renal biopsy reveals focal segmental glomerulosclerosis and diffuse mesangial sclerosis. Rarely, seizures, ataxia and dysmorphic features have been described.	Genetic otorhinolaryngologic disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder;Rare genetic renal disease
Orphanet:280384	Recessive intellectual disability-motor dysfunction-multiple joint contractures syndrome	ERLIN2	1	Recessive intellectual disability-motor dysfunction-multiple joint contractures syndrome is a rare, genetic, syndromic intellectual disabilty disorder characterized by severe intellectual disability, progressive, postnatal, multiple joint contractures and severe motor dysfunction. Patients present arrest and regression of motor function and speech acquisition, as well as contractures which begin in lower limbs and slowly progress in an ascending manner to include spine and neck, resulting in individuals presenting a specific fixed position.	Rare genetic neurological disorder
Orphanet:280397	Familial Alzheimer-like prion disease	PRNP	1	. Patients present with a prolonged, atypical course (absence of myoclonus or ataxia) unlike other forms of prion disease with severe neurofibrillary tangle pathology and high levels of cerebral amyloidosis.	Rare genetic neurological disorder
Orphanet:280576	Nestor-Guillermo progeria syndrome	BANF1	1	Nestor-Guillermo progeria syndrome is a rare, genetic, progeroid syndrome characterized by a prematurely aged appearance associated with severe osteolysis (notably on mandible, clavicles, ribs, distal phalanges, and long bones), osteoporosis, generalized lipoatrophy and absence of cardiovascular, atherosclerotic and metabolic complications, presenting a relatively long survival. Additional characteristics include growth retardation, joint stiffness (mainly of fingers, hands, knees, and elbows), wide cranial sutures, dysmorphic facial features (prominent eyes, convex nasal ridge, malocclusion, dental crowding, thin lip vermillion, microretrognathia) and persistent eyebrows, eyelashes and scalp hair.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic skin disease;Rare genetic endocrine disease
Orphanet:3220	Deafness-enamel hypoplasia-nail defects syndrome	PEX1;PEX6	2	Deafness-enamel hypoplasia-nail defects syndrome is characterised by sensorineural hearing loss, generalised enamel hypoplasia of the permanent dentition with normal primary dentition, and nail defects (Beau's lines and leukonychia). Less than 10 patients have been described so far. Transmission is autosomal recessive.	Genetic otorhinolaryngologic disease;Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:280586	Chondrodysplasia with joint dislocations, gPAPP type	IMPAD1	1	Chondrodysplasia with joint dislocations, gPAPP type is a rare, genetic, primary bone dysplasia characterized by prenatal onset of disproportionate short stature, shortening of the limbs, congenital joint dislocations, micrognathia, posterior cleft palate, brachydactyly, short metacarpals and irregular size of the metacarpal epiphyses, supernumerary carpal ossification centers and dysmorphic facial features. In addition, hearing impairment and mild psychomotor delay have also been reported.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:3221	Generalized resistance to thyroid hormone	THRB	1	NA	NA
Orphanet:280553	Fatal infantile hypertonic myofibrillar myopathy	CRYAB	1	Fatal infantile hypertonic myofibrillar myopathy is a rare, genetic skeletal muscle disease characterized by muscle stiffness and rigidity, hypertonia, weakness, respiratory distress and normal cognition. Patients have persistently elevated creatine kinase and histopathology is typical of myofibrillar myopathy. The manifestation onset follows the short period of normal infantile development and leads to progressive respiratory insufficiency and early death.	Rare genetic neurological disorder
Orphanet:280558	Warsaw breakage syndrome	DDX11	1	NA	Rare genetic developmental defect during embryogenesis;Inherited cancer-predisposing syndrome
Orphanet:647	Nijmegen breakage syndrome	NBN	1	Nijmegen breakage syndrome is a rare genetic disease presenting at birth with microcephaly, dysmorphic facial features, becoming more noticeable with age, growth delay, and later-onset complications such as malignancies and infections.	Rare genetic developmental defect during embryogenesis;Inherited cancer-predisposing syndrome;Rare genetic immune disease
Orphanet:279943	Hereditary neutrophilia	CSF3R	1	A rare, genetic, immune disease characterized by chronic neutrophilia, increase in the percentage of circulating CD34+ cells in peripheral blood, increase in granulocyte precursors in bone marrow and splenomegaly. Patients are predominantly asymptomatic, but may present with systemic inflammatory response syndrome with fever, dyspena, tachycardia, pleural and pericardial effusion, or myelodysplastic syndrome.	
Orphanet:279934	Mitochondrial DNA depletion syndrome, hepatocerebral form due to DGUOK deficiency	DGUOK	1	A rare immune disease characterized by severely reduced mitochondrial DNA content due to DGUOK deficiency typically manifesting with early-onset liver dysfunction, psychomotor delay, hypotonia, rotary nystagmus that develops into opsoclonus, lactic acidosis and hypoglycemia.	Rare inborn errors of metabolism;Rare genetic hepatic disease;Rare genetic developmental defect during embryogenesis;Rare genetic gastroenterological disease
Orphanet:3152	Sclerosteosis	SOST;LRP4	2	Sclerosteosis is a very rare serious sclerosing hyperostosis syndrome characterized clinically by variable syndactyly and progressive skeletal overgrowth (particularly of the skull), resulting in distinctive facial features (mandibular overgrowth, frontal bossing, midfacial hypoplasia), cranial nerve entrapment causing facial palsy and deafness, and potentially lethal elevation of intracranial pressure.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:280142	Severe combined immunodeficiency due to LCK deficiency	LCK	1	A rare, combined T- and B-cell immunodeficiency characterized by failure to thrive, severe diarrhea, opportunistic infections, and abnormal T-cell differentiation and function due to LCK deficiency, leading to an important risk factor for inflammation and autoimmunity.	Rare genetic immune disease
Orphanet:280133	Complement component 3 deficiency	C3	1	Complement component 3 deficiency is a rare, genetic, primary immunodeficiency characterized by susceptibility to infection (mainly by gram negative bacteria) due to extremely low C3 plasma levels. Patients typically present recurrent episodes of sinusitis, tonsillitis, and/or otitis, as well as upper and lower respiratory tract infections (including pneumonia) and skin infections, such as erythema multiforme. Autoimmune disease resembling systemic lupus erythematosus and mesangiocapillary or membranoproliferative glomerulonephritis may develop, resulting in renal failure.	Rare genetic immune disease
Orphanet:3163	SHORT syndrome	PIK3R1	1	A rare disorder characterized by multiple congenital anomalies. The name is a mneumonic for the common features observed in SHORT syndrome that include; short stature, hyperextensibility of joints, ocular depression, Rieger anomaly and teething delay. Other common manifestations of SHORT syndrome are mild intrauterine growth restriction, partial lipodystrophy, delayed bone age, hernias and a recognizable facial gestalt.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic endocrine disease;Rare genetic eye disease
Orphanet:1479	Atrial septal defect-atrioventricular conduction defects syndrome	NKX2-5	1	An extremely rare genetic congenital heart disease characterized by the presence of atrial septal defect, mostly of the ostium secundum type, associated with conduction anomalies like atrioventricular block, atrial fibrillation or right bundle branch block.	Rare genetic cardiac disease
Orphanet:3156	Senior-Loken syndrome	CEP290;INVS;IQCB1;NPHP1;NPHP3;NPHP4;SDCCAG8;WDR19;CEP164;TRAF3IP1	10	Senior-Loken syndrome (SLSN) is a very rare autosomal recessive oculo-renal disease characterized by the association of nephronophthisis (NPHP), a chronic kidney disease, with retinal dystrophy.	Rare genetic renal disease;Rare genetic eye disease;Ciliopathy
Orphanet:280071	ALG11-CDG	ALG11	1	 (13q14.3).	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:3157	Septo-optic dysplasia spectrum	PROKR2;SOX2;FGFR1;HESX1;OTX2;SOX3;ARNT2	7	Septooptic dysplasia (SOD) is a clinically heterogeneous disorder characterized by the classical triad of optic nerve hypoplasia, pituitary hormone abnormalities and midline brain defects.	Rare genetic eye disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease
Orphanet:280210	Pelizaeus-Merzbacher disease, connatal form	PLP1	1	The connatal form of Pelizaeus-Merzbacher disease (PMD) is the most severe form of PMD (see this term).	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:280219	Pelizaeus-Merzbacher disease, classic form	PLP1	1	The classic form of Pelizaeus-Merzbacher disease (PMD) is the infantile form of PMD.	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:280200	Microform holoprosencephaly	FGFR1;SUFU;PTCH1;SIX3;TGIF1;ZIC2;GLI2;TDGF1;FOXH1;FGF8;DISP1;CDON;NODAL;DLL1;GAS1;SHH	16	Microform holoprosencephaly is a benign form of holoprosencephaly (HPE; see this term) characterized by midline defects without the typical HPE defect in brain cleavage.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:3175	X-linked spasticity-intellectual disability-epilepsy syndrome	ARX	1	, Xp22.13).	Rare genetic neurological disorder
Orphanet:280195	Septopreoptic holoprosencephaly	PTCH1;SHH;SIX3;TGIF1;ZIC2;GLI2;TDGF1;FOXH1;FGF8;DISP1;CDON;NODAL;DLL1;GAS1	14	Septopreoptic holoprosencephaly (HPE) is a very rare subtype of lobar HPE (see this term) characterized by midline fusion limited to the septal and/or preoptic regions of the telencephalon without a significant frontal neocortical fusion.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease
Orphanet:280183	Methylmalonic aciduria due to transcobalamin receptor defect	CD320	1	Methylmalonic aciduria due to transcobalamin receptor defect is a rare metabolite absorption and transport disorder characterized by a moderate increase of methylmalonic acid (MMA) in the blood and urine due to decreased cellular uptake of cobalamin resulting from decreased transcobalamin receptor function. Patients are usually asymptomatic however, screening reveals increased C3-acylcarnitine and MMA in plasma. Serum homocysteine levels may vary from normal to moderately elevated and retinal vascular occlusive disease, resulting in severe visual loss, has been reported.	Rare inborn errors of metabolism
Orphanet:280282	Pelizaeus-Merzbacher-like disease due to GJC2 mutation	GJC2	1	NA	Rare genetic neurological disorder
Orphanet:280234	Null syndrome	PLP1	1	The null syndrome is part of the Pelizaeus-Merzbacher disease (PMD; see this term) spectrum and is characterized by mild PMD features associated with demyelinating peripheral neuropathy.	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:1855	Spondyloenchondrodysplasia	ACP5	1	Spondyloenchondrodysplasia (SPENCD) is a very rare genetic skeletal dysplasia characterized clinically by skeletal anomalies (short stature, platyspondyly, short broad ilia) and enchondromas in the long bones or pelvis. SPENCD may have a heterogeneous clinical spectrum with neurological involvement (spasticity, mental retardation and cerebral calcifications) or autoimmune manifestations, such as immune thrombocytopenic purpura, systemic lupus erythematosus (see these terms) hemolytic anemia and thyroiditis.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic immune disease;Rare genetic systemic or rheumatologic disease
Orphanet:280224	Pelizaeus-Merzbacher disease, transitional form	PLP1	1	The transitional form of Pelizaeus-Merzbacher disease (PMD) is the intermediate form of PMD (see this term).	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:1797	Autosomal dominant spondylocostal dysostosis	TBX6	1	A very rare and mild form of spondylocostal dysostosis characterized by vertebral and costal segmentation defects, often with a reduction in the number of ribs.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:280229	Pelizaeus-Merzbacher disease in female carriers	PLP1	1	 gene (Xq22).	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:276580	Autosomal dominant hyperinsulinism due to Kir6.2 deficiency	KCNJ11	1	A form of diazoxide-sensitive diffuse hyperinsulinism (DHI) characterized by hypoglycemic epiosodes that are usually mild, escaping detection during infancy, and usually a good clinical response to diazoxide, (but some are diazoxide resistant). Autosomal dominant hyperinsulinism due to Kir6.2 deficiency usually has a milder phenotype when compared to that resulting from recessive K+ (K-ATP) channel mutations (Recessive forms of diazoxide-resistant hyperinsulinism).	Rare genetic endocrine disease;Rare genetic developmental defect during embryogenesis
Orphanet:3258	Cenani-Lenz syndrome	APC;LRP4	2	Cenani-Lenz syndrome (CLS) is a congenital malformation syndrome that associates a complex syndactyly of the hands with malformations of the forearm bones and similar manifestations in the lower limbs.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:276575	Autosomal dominant hyperinsulinism due to SUR1 deficiency	ABCC8	1	A form of diazoxide-sensitive diffuse hyperinsulinism (DHI) characterized by hypoglycemic episodes that are usually mild, escaping detection during infancy, and usually present a good clinical response to diazoxide. Autosomal dominant hyperinsulinism due to SUR1 deficiency usually has a milder phenotype when compared to that resulting from recessive K-ATP mutations (recessive forms of Diazoxide-resistant hyperinsulinism).	Rare genetic endocrine disease;Rare genetic developmental defect during embryogenesis
Orphanet:276598	Diazoxide-resistant focal hyperinsulinism due to SUR1 deficiency	ABCC8	1	A rare, congenital, isolated hyperinsulinism disorder characterized by diazoxide unresponsive recurrent episodes of hyperinsulinemic hypoglycemia resulting from an excessive insulin secretion by the pancreatic bêta-cells due to SUR1 deficiency. Hypoglycemia may lead to variable clinical manifestations, ranging from asymptomatic hypoglycemia revealed by routine blood glucose monitoring to macrosomia at birth, mild to moderate hepatomegaly and life-threatening hypoglycemic coma or status epilepticus, further leading to poor neurological outcome.	Rare genetic endocrine disease;Rare genetic developmental defect during embryogenesis
Orphanet:276603	Diazoxide-resistant focal hyperinsulinism due to Kir6.2 deficiency	KCNJ11	1	A rare, congenital, isolated hyperinsulinism disorder characterized by diazoxide unresponsive recurrent episodes of hyperinsulinemic hypoglycemia resulting from an excessive insulin secretion by the pancreatic bêta-cells due to Kir6.2 deficiency. Hypoglycemia may lead to variable clinical manifestation, ranging from asymptomatic hypoglycemia revealed by routine blood glucose monitoring to macrosomia at birth, mild to moderate hepatomegaly and life-threatening hypoglycemic coma or status epilepticus, further leading to poor neurological outcome.	Rare genetic endocrine disease;Rare genetic developmental defect during embryogenesis
Orphanet:3267	Familial lambdoid synostosis	ERF	1	Familial lambdoid synostosis is a rare, genetic cranial malformation characterized by unilateral or bilateral synostosis of the lambdoid suture in multiple members of a single family. Unilateral cases typically present ipsilateral occipitomastoid bulge, compensatory contralateral parietal and frontal bossing, displacement of one ear, lateral deviation of jaw and compensatory deformation of cervical spine while bilateral cases usually manifest with flat and widened occiput, displacement of both ears and frequent occurrence of raised intracranial pressure.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:276624	Sporadic pheochromocytoma	EPAS1;VHL;RET;SDHD;SDHB	5	A rare tumor of endocrine glands characterized, typically, by a unicentric, unilateral, sporadic, catecholamine-secreting neuroendocrine tumor, arising from chromaffin cells of the adrenal medulla, presenting with highly variable and non-specific manifestations, including hypertension (that can be paroxysmal, persistent, or resistant), cephalea, heart palpitations, anxiety, diaphoresis, unexplained fever, chronic fatigue and weakness, among others.	
Orphanet:276630	Symptomatic form of Coffin-Lowry syndrome in female carriers	RPS6KA3	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease;Rare genetic neurological disorder
Orphanet:276627	Sporadic secreting paraganglioma	EPAS1	1	A rare tumor of endocrine glands characterized by a sporadic, extra-adrenal, catecholamine-secreting, chromaffin cell tumor located anywhere along the sympathetic ganglia (most frequently in the abdomen and pelvis), typically manifesting with episodic hypertension, cephalea, diaphoresis, heart palpitations, and, occasionally, hyperglycemia, anxiety/panic attacks, fever, weight loss, myocardial infarction, osteolytic bone metastases, and Raynaud's phenomenon.	
Orphanet:3275	Spondylocarpotarsal synostosis	MYH3;FLNB	2	A spondylodysplasic dysplasia clinically characterized by postnatal progressive vertebral fusions frequently manifesting as block vertebrae, contributing to an shortened trunk and hence disproportionate short stature, scoliosis, lordosis, carpal and tarsal synostosis and infrequently, club feet.	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:425	Apolipoprotein A-I deficiency	APOA1;ABCA1	2	A rare lipoprotein metabolism disorder characterized biochemically by complete absence of apolipoprotein AI and extremely low plasma high density lipoprotein (HDL) cholesterol, and clinically by corneal opacities and xanthomas complicated with premature coronary heart disease (CHD).	Rare inborn errors of metabolism;Rare genetic endocrine disease
Orphanet:3301	Tetraamelia-multiple malformations syndrome	RSPO2;WNT3	2	Tetraamelia - multiple malformations is an extremely rare mostly lethal congenital disorder characterized by absence of all four limbs and frequent associated major malformations involving the head, face, eyes, skeleton, heart, lungs, anus, urogenital, and central nervous systems. The syndrome has been described in fewer than 20 patients mainly of middle Eastern descent.	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic bone disease
Orphanet:276198	Spinocerebellar ataxia type 36	NOP56	1	Spinocerebellar ataxia type 36 (SCA36) is a subtype of autosomal dominant cerebellar ataxia type 1 (ADCA type 1; see this term) characterized by gait and limb ataxia, lower limb spasticity, dysarthria, muscle fasiculations, tongue atrophy and hyperreflexia.	Rare genetic neurological disorder
Orphanet:3226	Deafness-lymphedema-leukemia syndrome	GATA2	1	Deafness - lymphedema - leukemia is a very rare, serious syndromic genetic disorder characterized by primary lymphedema, immunodeficiency, and hematological disorders.	Genetic otorhinolaryngologic disease;Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:276193	Spinocerebellar ataxia type 35	TGM6	1	Spinocerebellar ataxia type 35 (SCA35) is a subtype of autosomal dominant cerebellar ataxia type 1 (ADCA type 1; see this term) characterized by the adult-onset of progressive gait and limb ataxia, dysarthria, ocular dysmetria, intention tremor, hyperreflexia and spasmodic torticollis.	Rare genetic neurological disorder
Orphanet:276183	Spinocerebellar ataxia type 32	SCA32	1	Spinocerebellar ataxia type 32 (SCA32) is a subtype of autosomal dominant cerebellar ataxia type 1 (ADCA type 1; see this term) characterized by ataxia, cognitive impairment and azoospermia in males.	Rare genetic neurological disorder
Orphanet:276238	Machado-Joseph disease type 1	ATXN3	1	Machado-Joseph disease type 1 is a rare, usually severe subtype of Machado-Joseph disease (SCA3/MJD, see this term) characterized by the presence of marked pyramidal and extrapyramidal signs.	Rare genetic neurological disorder
Orphanet:276234	Non-syndromic male infertility due to sperm motility disorder	WDR66;CFAP43;CFAP44;AK7;CFAP69;SPAG17;CATSPER1;SLC26A8;SEPT12;DNAH1	10	Non-syndromic male infertility due to sperm motility disorder is a rare, genetic, non-syndromic male infertility disorder characterized by infertility due to sperm with defects in their cilia/flagella structure, leading to absent motility or reduced forward motility in fresh ejaculate. Reduced semen volume, oligospermia and an increased number of abnormally structured spermatozoa is often present.	Genetic infertility
Orphanet:276223	Mucopolysaccharidosis type 6, slowly progressing	ARSB	1	NA	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:276212	Mucopolysaccharidosis type 6, rapidly progressing	ARSB	1	NA	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:276244	Machado-Joseph disease type 3	ATXN3	1	Machado-Joseph disease type 3 is a subtype of Machado-Joseph disease (SCA3/MJD, see this term) of milder severity characterized by late onset, slower progression, and peripheral amyotrophy.	Rare genetic neurological disorder
Orphanet:276241	Machado-Joseph disease type 2	ATXN3	1	Machado-Joseph disease type 2 is a subtype of Machado-Joseph disease (SCA3/MJD, see this term) with intermediate severity characterized by an intermediate age of onset, cerebellar ataxia and external progressive ophthalmoplegia, with variable pyramidal and extrapyramidal signs.	Rare genetic neurological disorder
Orphanet:276280	Hemihyperplasia-multiple lipomatosis syndrome	PIK3CA	1	Hemihyperplasia-multiple lipomatosis syndrome is a rare, genetic overgrowth syndrome characterized by non- progressive, asymmetrical, moderate hemihyperplasia (frequently affecting the limbs) associated with slow growing, painless, multiple, recurrent, subcutaneous lipomatous masses distributed throughout entire body (in particular back, torso, extremities, fingers, axillae). Superficial vascular malformations may also be associated. Increased risk of intra-abdominal embryonal malignancies may be associated.	Rare genetic tumor;Rare genetic developmental defect during embryogenesis
Orphanet:276399	Familial multinodular goiter	KEAP1;DICER1	2	NA	Rare genetic endocrine disease
Orphanet:3238	Cardiospondylocarpofacial syndrome	MAP3K7	1	Cardiospondylocarpofacial syndrome is characterized by mitral insufficiency, conductive deafness, short stature, and skeletal anomalies (bony fusion involving the cervical vertebrae, the ossicles, and the carpal and tarsal bones). It has been described in three members of one family. The mode of inheritance is likely to be autosomal dominant with incomplete penetrance.	Genetic otorhinolaryngologic disease
Orphanet:3237	Multiple synostoses syndrome	GDF5;NOG;FGF9	3	Multiple synostoses syndrome (MSS) is a rare developmental bone disorder characterized by proximal symphalangism of the fingers and/or toes often associated with fusion of carpal and tarsal, humeroradial, and cervical spine joints.	Genetic otorhinolaryngologic disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:276405	Hyperbiliverdinemia	BLVRA	1	Hyperbiliverdinemia is a rare, genetic hepatic disease characterized by the presence of green coloration of the skin, urine, plasma and other body fluids (ascites, breastmilk) or parts (sclerae) due to increased serum levels of biliverdin in association with biliary obstruction and/or liver failure. Association with malnutrition, medication, and congenital biliary atresia has also been reported.	
Orphanet:3250	Proximal symphalangism	GDF5;NOG	2	Proximal symphalangism is a very rare, genetic bone disorder characterized by ankylosis of the proximal interphalangeal joints, carpal and tarsal bone fusion, and conductive hearing loss in some patients.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:276556	Hyperinsulinism due to UCP2 deficiency	UCP2	1	HyHyperinsulism due to UCP2 deficiency (HIUCP2) is a form of diazoxide-sensitive diffuse hyperinsulinism (DHI, see this term) characterized by hypoglycemic episodes from the neonatal period, a good clinical response to diazoxide and a probable transient nature of the disease with spontaneous resolution.	Rare genetic endocrine disease;Rare genetic developmental defect during embryogenesis
Orphanet:3255	Filippi syndrome	CKAP2L	1	Filippi syndrome is characterised by microcephaly, cutaneous syndactyly of the fingers and toes, intellectual deficit, growth retardation and a characteristic facies (high and broad nasal bridge, thin alae nasi, micrognathia and a high frontal hairline). So far, less than 25 cases have been reported. Cryptorchidism, polydactyly, and teeth and hair anomalies may also be present. Transmission is autosomal recessive.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:276432	Ogden syndrome	NAA10	1	Ogden syndrome is a rare, genetic progeroid syndrome characterized by a variable phenotype including postnatal growth delay, severe global developmental delay, hypotonia, non-specific dysmorphic facies with aged appearance and cryptorchidism, as well as cardiac arrthymias and skeletal anomalies. Patients typically present with widely opened fontanels, mainly truncal hypotonia, a waddling gait with hypertonia of the extremities, small hands and feet, broad great toes, scoliosis and redundant skin with lack of subcutaneous fat.	Rare genetic developmental defect during embryogenesis
Orphanet:276435	Lower motor neuron syndrome with late-adult onset	CHCHD10	1	A rare, genetic, motor neuron disease characterized by slowly progressive, predominantly proximal, muscular weakness and atrophy which typically manifests with muscle cramps, fasciculations, decreased/absent deep tendon reflexes, hand tremor, and elevated serum creatine kinase at onset and later associates gait disturbances and impaired vibration sensation.	Rare genetic neurological disorder
Orphanet:3253	Zlotogora-Ogur syndrome	NECTIN1	1	Zlotogora-Ogur syndrome is an ectodermal dysplasia syndrome characterized by hair, skin and teeth anomalies, facial dysmophism with cleft lip and palate, cutaneous syndactyly and, in some cases, intellectual disability.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:911	Combined immunodeficiency due to ZAP70 deficiency	ZAP70	1	A very rare, severe, genetic, combined immunodeficiency disorder characterized by lymphocytosis, decreased peripheral CD8+ T-cells, and presence of normal circulating CD4+ T-cells, leading to immune dysfunction.	Rare genetic immune disease
Orphanet:746	Mitochondrial trifunctional protein deficiency	HADHA;HADHB	2	A rare disorder of fatty acid oxidation characterized by a wide clinical spectrum ranging from severe neonatal manifestations including cardiomyopathy, hypoglycemia, metabolic acidosis, skeletal myopathy and neuropathy, liver disease and death to a mild phenotype with peripheral polyneuropathy, episodic rhabdomyolysis and pigmentary retinopathy..	Rare genetic neurological disorder;Rare genetic cardiac disease;Rare inborn errors of metabolism
Orphanet:943	Malonic aciduria	MLYCD	1	Malonic aciduria is a metabolic disorder caused by deficiency of malonyl-CoA decarboxylase (MCD).	Rare inborn errors of metabolism
Orphanet:621	Hereditary methemoglobinemia	CYB5R3;CYB5A	2	A rare red cell disorder classified principally into two clinical phenotypes: autosomal recessive congenital (or hereditary) methemoglobinemia types I and II (RCM/RHM type 1; RCM/RHM type 2).	Rare genetic hematologic disease
Orphanet:2089	Glycogen storage disease due to hepatic glycogen synthase deficiency	GYS2	1	A genetically inherited anomaly of glycogen metabolism and a form of glycogen storage disease (GSD) characterized by fasting hypoglycemia. This is not a glycogenosis, strictly speaking, as the enzyme deficiency decreases glycogen reserves.	Rare inborn errors of metabolism
Orphanet:412	Dysbetalipoproteinemia	APOE	1	A rare combined hyperlipidemia (HLP type 3) characterized by high levels of cholesterol and triglycerides, transported by intermediate density lipoproteins (IDLs), and a high risk of progressive atherosclerosis and premature cardiovascular disease.	Rare inborn errors of metabolism;Rare genetic endocrine disease
Orphanet:743	Severe hereditary thrombophilia due to congenital protein S deficiency	PROS1	1	An inherited coagulation disorder characterized by recurrent venous thrombosis symptoms due to reduced synthesis and/or activity levels of protein S.	Rare genetic hematologic disease;Rare genetic bone disease
Orphanet:424	Familial hyperthyroidism due to mutations in TSH receptor	TSHR	1	A rare hyperthyroidism characterized by mild to severe hyperthyroidism, presence of goiter, absence of features of autoimmunity, frequent relapses while on treatment and a positive family history.	Rare genetic renal disease;Rare genetic endocrine disease
Orphanet:325	Congenital factor II deficiency	F2	1	An inherited bleeding disorder due to reduced activity of factor II (FII, prothrombin) and characterized by mucocutaneous bleeding symptoms.	Rare genetic hematologic disease
Orphanet:343	Hyperimmunoglobulinemia D with periodic fever	MVK	1	A rare autoinflammatory disease characterized by periodic attacks of fever and a systemic inflammatory reaction (cervical lymphadenopathy, abdominal pain, vomiting, diarrhea, arthralgias and skin signs).	Rare genetic immune disease;Rare genetic systemic or rheumatologic disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:572	Immunodeficiency by defective expression of MHC class II	RFX5;RFXANK;RFXAP;CIITA	4	A rare primary genetic immunodeficiency disorder characterized by partial or complete absence of human leukocyte antigen class 2 expression resulting in severe defect in both cellular and humoral immune response to antigens. The disorder presents clinically as marked susceptibility to infections, severe malabsorption and failure to thrive and is often fatal in early childhood.	Rare genetic immune disease
Orphanet:1930	Herpes simplex virus encephalitis	UNC93B1;TLR3;TICAM1;TRAF3;TBK1	5	A rare disorder caused by infection of the central nervous system by Herpes simplex virus (HSV) that could have a devastating clinical course and a potentially fatal outcome particularly with delay or lack of treatment. This disorder often involves the frontal and temporal lobes, usually asymmetrically, resulting in personality changes, cognitive impairment, aphasia, seizures, and focal weakness.	Rare genetic immune disease
Orphanet:158	Systemic primary carnitine deficiency	SLC22A5	1	A disorder of carnitine cycle and carnitine transport that is characterized classically by early childhood onset cardiomyopathy often with weakness and hypotonia, failure to thrive and recurrent hypoglycemic hypoketotic seizures and/or coma.	Rare inborn errors of metabolism;Rare genetic neurological disorder;Rare genetic cardiac disease
Orphanet:2056	Essential fructosuria	KHK	1	Essential fructosuria is a rare autosomal recessive disorder of fructose metabolism (see this term) caused by a deficiency of fructokinaseenzyme activity. It is characterized by elevated fructosemia and presence of fructosuria following ingestion of fructose and related sugars (sucrose, sorbitol). Essential fructosuria is clinically asymptomatic and harmless. Dietary restriction is not indicated.	Rare inborn errors of metabolism
Orphanet:206436	Infantile Krabbe disease	PSAP;GALC	2	NA	Rare genetic neurological disorder;Rare genetic eye disease;Rare inborn errors of metabolism
Orphanet:820	Sneddon syndrome	ADA2	1	Sneddon's syndrome (SS) is a rare non-inflammatory thrombotic vasculopathy characterized by the combination of cerebrovascular disease with livedo racemosa.	
Orphanet:1945	Rolandic epilepsy	GABRG2;GRIN2A;SRPX2	3	Rolandic epilepsy (RE) is a focal childhood epilepsy characterized by seizures consisting of unilateral facial sensory-motor symptoms, with electroencephalogram (EEG) showing sharp biphasic waves over the rolandic region. It is an age-related epilepsy, with excellent outcome.	Rare genetic neurological disorder
Orphanet:440	OBSOLETE: Familial hypospadias	AR;MAMLD1	2	NA	NA
Orphanet:832	Succinyl-CoA:3-ketoacid CoA transferase deficiency	OXCT1	1	Succinyl-CoA:3-ketoacid CoA transferase deficiency (SCOTD) is a defect in ketone body utilization characterized by severe, potentially fatal intermittent episodes of ketoacidosis.	Rare inborn errors of metabolism
Orphanet:6	3-methylcrotonyl-CoA carboxylase deficiency	MCCC1;MCCC2	2	3-methylcrotonyl-CoA carboxylase deficiency (3-MCCD) is an inherited disorder of leucine metabolism characterized by a highly variable clinical picture ranging from metabolic crisis in infancy to asymptomatic adults.	Rare inborn errors of metabolism
Orphanet:20	3-hydroxy-3-methylglutaric aciduria	HMGCL	1	3-hydroxy-3-methylglutaric aciduria (3HMG) is an organic aciduria, due to deficiency of 3-hydroxy-3-methylglutaryl-CoA-lyase (a key enzyme in ketogenesis and leucine metabolism) usually presenting in infancy with episodes of metabolic decompensation triggered by periods of fasting or infections, which when left untreated are life-threatening and may lead to neurological sequelae.	Rare inborn errors of metabolism
Orphanet:714	Hemolytic anemia due to diphosphoglycerate mutase deficiency	BPGM	1	NA	Rare inborn errors of metabolism;Rare genetic hematologic disease
Orphanet:712	Hemolytic anemia due to glucophosphate isomerase deficiency	GPI	1	Glucosephosphate isomerase (GPI) deficiency is an erythroenzymopathy characterized by chronic nonspherocytic hemolytic anemia.	Rare inborn errors of metabolism;Rare genetic hematologic disease
Orphanet:206546	Symptomatic form of muscular dystrophy of Duchenne and Becker in female carriers	DMD	1	Symptomatic forms of Duchenne and Becker muscular dystrophies (DMD and BMD: see these terms) in females carriers are characterized by variable degrees of muscle weakness due to progressive skeletal myopathy, sometimes associated with dilated cardiomyopathy or left ventricle dilation.	Rare genetic neurological disorder;Rare genetic cardiac disease
Orphanet:206554	Autosomal recessive limb-girdle muscular dystrophy type 2M	FKTN	1	A form of limb-girdle muscular dystrophy characterized by an infantile onset of hypotonia, axial and proximal lower limb weakness (with severe weakness noted after febrile illnesses), cardiomyopathy and normal or reduced intelligence. Hypertrophy of calves, thighs, and triceps have also been reported in some cases.	Rare genetic cardiac disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:206549	Autosomal recessive limb-girdle muscular dystrophy type 2L	ANO5	1	A form of limb-girdle muscular dystrophy most often characterized by an adult onset (but ranging from 11 to 51 years) of mainly proximal lower limb weakness, with difficulties standing on tiptoes being one of the initial signs. Proximal upper limb and distal lower limb weakness is also common, as well as atrophy of the quadriceps (most commonly), biceps brachii, and lower leg muscles. Calf hypertrophy has also been reported in some cases. LGMD2L progresses slowly, with most patients remaining ambulatory until late adulthood.	Rare genetic neurological disorder
Orphanet:206564	Autosomal recessive limb-girdle muscular dystrophy type 2O	POMGNT1	1	A form of limb-girdle muscular dystrophy characterized by an onset in childhood or adolescence of rapidly progressive proximal limb muscle weakness (particularly affecting the neck, hip girdle, and shoulder abductors), hypertrophy in the calves and quadriceps, ankle contractures, and myopia.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:206559	Autosomal recessive limb-girdle muscular dystrophy type 2N	POMT2	1	A form of limb-girdle muscular dystrophy characterized by proximal weakness (manifesting as slowness in running) presenting in infancy, along with calf hypertrophy, mild lordosis, scapular winging and normal intelligence (or mild intellectual disability).	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:206580	Autosomal recessive lower motor neuron disease with childhood onset	PLEKHG5	1	A rare, genetic, neuromuscular disease characterized by proximal muscle weakness with an early involvement of foot and hand muscles following normal motor development in early childhood, a rapidly progressive disease course leading to generalized areflexic tetraplegia with contractures, severe scoliosis, hyperlordosis, and progressive respiratory insufficiency leading to assisted ventilation. Cranial nerve functions are normal and tongue wasting and fasciculations are absent. Milder phenotype with a moderate generalized weakness and slower disease progress was reported.	Rare genetic neurological disorder
Orphanet:206443	Late-infantile/juvenile Krabbe disease	GALC	1	NA	Rare genetic neurological disorder;Rare genetic eye disease;Rare inborn errors of metabolism
Orphanet:206448	Adult Krabbe disease	GALC	1	NA	Rare genetic neurological disorder;Rare genetic eye disease;Rare inborn errors of metabolism
Orphanet:2680	Hypomyelination neuropathy-arthrogryposis syndrome	CNTNAP1;ADCY6;LGI4	3	10 m/s) are frequently associated. Nerve ultrastructural morphology shows severe abnormalities of the nodes of Ranvier and myelinated axons.	Rare genetic developmental defect during embryogenesis
Orphanet:633	Laron syndrome	GHR	1	Laron syndrome is a congenital disorder characterized by marked short stature associated with normal or high serum growth hormone (GH) and low serum insulin-like growth factor-1 (IGF-I) levels which fail to rise after exogenous GH administration.	Rare genetic endocrine disease
Orphanet:478	Kallmann syndrome	CCDC141;PROK2;PROKR2;CHD7;SOX10;FGFR1;HESX1;ANOS1;KISS1R;NSMF;FGF8;WDR11;HS6ST1;SEMA3A;IL17RD;FGF17;DUSP6;SPRY4;FLRT3;FEZF1;DCC;TACR3;CCDC141	23	Kallmann syndrome (KS) is a developmental genetic disorder characterized by the association of congenital hypogonadotropic hypogonadism (CHH) due to gonadotropin-releasing hormone (GnRH) deficiency, and anosmia or hyposmia (with hypoplasia or aplasia of the olfactory bulbs).	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility
Orphanet:822	Hereditary spherocytosis	SLC4A1;SPTA1;SPTB;ANK1;EPB42	5	Hereditary spherocytosis is a congenital hemolytic anemia with a wide clinical spectrum (from symptom-free carriers to severe hemolysis) characterized by anemia, variable jaundice, splenomegaly and cholelithiasis.	Rare genetic hematologic disease
Orphanet:910	Xeroderma pigmentosum	XPA;ERCC3;XPC;DDB2;ERCC4;ERCC5;ERCC2	7	Xeroderma pigmentosum (XP) is a rare genodermatosis characterized by extreme sensitivity to ultraviolet (UV)-induced changes in the skin and eyes, and multiple skin cancers. It is subdivided into 8 complementation groups, according to the affected gene: classical XP (XPA to XPG) and XP variant (XPV) (see these terms).	Inherited cancer-predisposing syndrome;Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare genetic skin disease;Rare genetic eye disease
Orphanet:229	Familial aortic dissection	MYH11	1	Familial aortic dissection is the term used to describe rupture of the aortic wall at the level of the media, resulting in the formation of a false channel and deviation of part of the aortic flux. Familial predisposition to thoracic aortic aneurysms and type A dissections (concerning the ascending aorta and/or the aortic arch) has been demonstrated in around 19% of patients presenting with thoracic aortic dissections and several loci have been identified so far (16p12.2-p13.13, 3p24-25). This predisposition is transmitted in an autosomal dominant manner.	Rare genetic vascular disease
Orphanet:777	X-linked non-syndromic intellectual disability	CXORF56;RPS6KA3;ARX;DMD;FTSJ1;GDI1;MED12;UPF3B;AGTR2;ZNF41;DLG3;IL1RAPL1;PAK3;TSPAN7;ARHGEF6;ZNF81;SYP;ZNF711;RAB39B;HCFC1;ALG13;MID2;PTCHD1;USP9X;ACSL4;MECP2;IQSEC2;CNKSR2;FRMPD4;USP27X;CLCN4	31	NA	Rare genetic neurological disorder
Orphanet:766	Hemolytic anemia due to red cell pyruvate kinase deficiency	PKLR	1	Hemolytic anemia due to red cell pyruvate kinase (PK) deficiency is a metabolic disorder characterized by a variable degree of chronic nonspherocytic hemolytic anemia.	Rare genetic hematologic disease;Rare inborn errors of metabolism
Orphanet:206599	Isolated asymptomatic elevation of creatine phosphokinase	CAV3	1	Isolated asymptomatic elevation of creatine phosphokinase is a rare neurologic disease characterized by persistent elevation of the serum creatine phosphokinase (CK) without any clinical, neurophysical or histopathological evidence of neuromuscular disease using the available laboratory procedures. It is usually an incidental finding, diagnosed after exclusion of other possible causes of elevated CK levels.	Rare genetic neurological disorder
Orphanet:3206	Stüve-Wiedemann syndrome	LIFR	1	Stüve-Wiedemann syndrome (SWS) is a rare autosomal recessive congenital primary skeletal dysplasia, characterized by small stature, bowing of the long bones, camptodactyly, hyperthermic episodes, respiratory distress/apneic episodes and feeding difficulties that usually lead to early mortality.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:206583	Adult polyglucosan body disease	GBE1	1	A glycogen storage disease of adults characterized by progressive upper and lower motor neuron dysfunction, progressive neurogenic bladder and cognitive difficulties that can lead to dementia.	Rare genetic neurological disorder;Rare genetic hepatic disease;Rare genetic cardiac disease;Rare inborn errors of metabolism
Orphanet:65	Leber congenital amaurosis	SPATA7;GDF6;IFT140;NMNAT1;RD3;RDH12;RPE65;RPGRIP1;CEP290;AIPL1;TULP1;CRB1;CRX;GUCY2D;IMPDH1;IQCB1;LCA5;KCNJ13;LRAT;PCYT1A	20	Leber congenital amaurosis (LCA) is a retinal dystrophy defined by blindness and responses to electrophysiological stimulation (Ganzfeld electroretinogram (ERG)) below threshold, associated with severe visual impairment within the first year of life.	Rare genetic eye disease;Ciliopathy
Orphanet:321	Multiple osteochondromas	EXT1;EXT2	2	Multiple osteochondromas (MO) is characterised by development of two or more cartilage capped bony outgrowths (osteochondromas) of the long bones.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic tumor;Rare inborn errors of metabolism
Orphanet:144	Lynch syndrome	KRAS;PMS1;PMS2;TGFBR2;MLH1;MLH3;MSH2;MSH6;EPCAM;FAN1;PIK3CA	11	NA	Rare genetic tumor;Inherited cancer-predisposing syndrome
Orphanet:110	Bardet-Biedl syndrome	BBS1;BBS10;BBS2;BBS4;BBS5;BBS7;BBS9;CEP290;TRIM32;TTC8;ARL6;MKKS;MKS1;NPHP1;BBS12;SDCCAG8;WDPCP;LZTFL1;IFT172;BBIP1;IFT27;C8ORF37	22	Bardet-Biedl syndrome (BBS) is a ciliopathy with multisystem involvement.	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic gastroenterological disease;Ciliopathy;Rare genetic renal disease
Orphanet:3095	Atypical Rett syndrome	MECP2;FOXG1;NTNG1;CDKL5;STXBP1;GABBR2	6	A rare neurodevelopmental disorder that is diagnosed when a child presents with a Rett-like syndrome but does not fulfill all the diagnostic criteria for typical Rett syndrome (classic/typical RTT).	Rare genetic neurological disorder
Orphanet:1114	Aplasia cutis congenita	BMS1;DLL4	2	A rare skin disorder characterized by localized absence of skin that is usually located on the scalp but can occur anywhere on the body including the face, trunk and extremities. Aplasia cutis congenita (ACC) may occasionally be associated with other anomalies.	Rare genetic skin disease
Orphanet:208513	Spinocerebellar ataxia type 29	ITPR1	1	Spinocerebellar ataxia type 29 (SCA29) is a rare subtype of autosomal dominant cerebellar ataxia type I (ADCA type I; see this term) characterized by very slowly progressive or non-progressive ataxia, dysarthria, oculomotor abnormalities and intellectual disability.	Rare genetic neurological disorder
Orphanet:3051	Intellectual disability-sparse hair-brachydactyly syndrome	SMARCA2	1	Intellectual disability-sparse hair-brachydactyly syndrome is a very rare condition of unknown etiology consisting of short stature, hypotrichosis, brachydactyly with cone-shaped epiphyses, epilepsy and severe mental delay. After the initial delineation of this syndrome by Nicolaides and Baraitser in 1993, only five more patients were published in the literature up to now.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:208447	Bilateral generalized polymicrogyria	GRIN1	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:208441	Bilateral parasagittal parieto-occipital polymicrogyria	FIG4	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:2963	Progeroid syndrome, Petty type	SLC25A24	1	Progeroid syndrome, Petty type is a rare premature aging syndrome characterized by pre-and postnatal growth retardation, a congenital premature-aged appearance with distinctive craniofacial dysmorphism (wide calvaria with large open anterior fontanel and wide metopic suture, broad forehead, small face, micrognathia), markedly diminished subcutaneous fat, cutis laxa and wrinkled skin, without delay in psychomotor development. Scant, brittle hair, hypoplastic nails and delayed, abnormal dentition, as well as hypoplastic distal phalanges, umbilical hernia and eye abnormalities (myopia/hyperopia, strabismus), are also commonly associated.	Rare genetic eye disease;Rare genetic skin disease
Orphanet:1541	Craniosynostosis, Boston type	MSX2	1	Craniosynostosis, Boston type is a form of syndromic craniosynostosis, characterized by a highly variable craniosynostosis with frontal bossing, turribrachycephaly and cloverleaf skull anomaly. Hypoplasia of the supraorbital ridges, cleft palate, extra teeth and limb anomalies (triphalangeal thumb, 3-4 syndactyly of the hands, a short first metatarsal, middle phalangeal agenesis in the feet) have also been described. Associated problems include headache, poor vision, and seizures. Intelligence is normal.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2151	Hirschsprung disease-ganglioneuroblastoma syndrome	PHOX2B	1	A rare, genetic, developmental defect during embryogenesis syndrome characterized by total or partial colonic aganglionosis associated with peripheral, usually multifocal, neuroblastic tumors (ganglioneuroblastoma, neuroblastoma, ganglioneuroma). Congenital central hypoventilation syndrome, with variable severity of respiratory compromise, cardiovascular and ophthalmologic symptoms, consistent with autonomic nervous system dysfunction, is occasionally associated.	Rare genetic gastroenterological disease;Rare genetic eye disease
Orphanet:209335	Autosomal dominant adult-onset proximal spinal muscular atrophy	VAPB	1	A rare, genetic, motor neuron disease characterized by adulthood-onset of slowly progressive, proximal muscular weakness with fasciculations, amyotrophy, cramps, and absent/hypoactive reflexes, without bulbar or pyramidal involvement.	Rare genetic neurological disorder
Orphanet:209341	DYNC1H1-related autosomal dominant childhood-onset proximal spinal muscular atrophy	DYNC1H1	1	NA	Rare genetic neurological disorder
Orphanet:210110	Intermediate osteopetrosis	TCIRG1;CLCN7;PLEKHM1	3	Intermediate osteopetrosis is a rare, genetic primary bone dysplasia with increased bone density characterized by susceptibility to fractures after minor trauma, anemia, and characteristic skeletal radiographic changes, such as sandwich vertebra, bone-within-bone appearance, Erlenmeyer-shaped femoral metaphysis, and mild osteosclerosis of the skull base. Dental anomalies and visual impairment secondary to optic nerve compression have been rarely described.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:210115	Sterile multifocal osteomyelitis with periostitis and pustulosis	IL1RN	1	Sterile multifocal osteomyelitis with periostitis and pustulosis is a rare, severe, genetic autoinflammatory syndrome characterized by usually neonatal onset of generalized neutrophilic cutaneous pustulosis and severe, recurrent, multifocal, aseptic osteomyelitis with marked periostitis, typically affecting distal ribs, long bones and vertebral bodies. High levels of acute-phase reactants (with no fever associated) and onychosis are frequently observed additional features.	Rare genetic immune disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:209981	IRIDA syndrome	TMPRSS6	1	IRIDA (Iron-refractory iron deficiency anemia) syndrome is a rare autosomal recessive iron metabolism disorder characterized by iron deficiency anemia (hypochromic, microcytic) that is often unresponsive to oral iron intake and partially responsive to parenteral iron treatment.	Rare genetic hematologic disease
Orphanet:210122	Congenital alveolar capillary dysplasia	FOXF1	1	Congenital alveolar capillary dysplasia (ACD) is a rare and fatal developmental lung disease characterized by respiratory distress in neonates due to refractory hypoxemia and severe pulmonary arterial hypertension.	Rare genetic respiratory disease
Orphanet:210128	Urocanic aciduria	UROC1	1	Encephalopathy due to urocanase deficiency is an extremely rare histidine metabolism disorder characterized by urocanic aciduria and other variable manifestations including intellectual deficit and intermittent ataxia in the 4 cases reported to date.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:2254	Pontocerebellar hypoplasia type 1	RARS2;TSEN54;VRK1;EXOSC3;EXOSC8;EXOSC9	6	Pontocerebellar hypoplasia type 1 (PCH1), also known as Norman's disease, is a clinically and genetically heterogeneous group of autosomal recessive disorders with a prenatal onset characterized by diffuse muscular atrophy secondary to pontocerebellar hypoplasia and spinal cord anterior horn cell degeneration resulting in early death.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:209951	Autosomal recessive spastic paraplegia type 18	ERLIN2	1	 gene (8p11.2) encoding the protein, Erlin-2.	Rare genetic neurological disorder
Orphanet:209967	Episodic ataxia type 6	SLC1A3	1	Episodic ataxia type 6 (EA6) is an exceedingly rare form of Hereditary episodic ataxia (see this term) with varying degrees of ataxia and associated findings including slurred speech, headache, confusion and hemiplegia.	Rare genetic neurological disorder
Orphanet:209908	Childhood apraxia of speech	FOXP2	1	NA	
Orphanet:209905	Brain-lung-thyroid syndrome	NKX2-1	1	Brain-lung-thyroid syndrome is a rare disorder characterized by congenital hypothyroidism (CH), infant respiratory distress syndrome (IRDS) and benign hereditary chorea (BHC; see these terms).	Rare genetic neurological disorder;Rare genetic endocrine disease;Rare genetic respiratory disease
Orphanet:209902	Hypercholesterolemia due to cholesterol 7alpha-hydroxylase deficiency	CYP7A1	1	Hypercholesterolemia due to cholesterol 7alpha-hydroxylase deficiency is a rare, genetic, sterol metabolism disorder characterized by increased LDL cholesterol serum levels (which are resistant to treatment with 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors), hypertrigliceridemia, and decreased rate of bile acid excretion, resulting from cholesterol 7alpha-hydroxylase deficiency. Premature gallstone disease and/or premature coronary and peripheral vascular disease are frequently associated.	Rare inborn errors of metabolism;Rare genetic endocrine disease
Orphanet:209932	Cone dystrophy with supernormal rod response	KCNV2	1	Cone dystrophy with supernormal rod response (CDSRR) is an inherited retinopathy, with an onset in the first or second decade of life, characterized by poor visual acuity (due to central scotoma), photophobia, severe dyschromatopsia, and occasionally, nystagmus. Night blindness usually develops later in the course of the disease, but it can also be apparent from childhood. A hallmark of CDSRR is the decreased and delayed dark-adapted response to dim flashes in electroretinographic recordings, which contrasts with the supernormal b-wave response at the highest levels of stimulation.	Rare genetic eye disease
Orphanet:209916	Extraskeletal myxoid chondrosarcoma	TFG;EWSR1;TCF12;NR4A3;TAF15	5	NA	
Orphanet:209370	Severe neonatal-onset encephalopathy with microcephaly	MECP2	1	Severe neonatal-onset encephalopathy with microcephaly is a rare monogenic disease with epilepsy characterized by neonatal-onset encephalopathy, microcephaly, severe developmental delay or absent development, breathing abnormalities (including central hypoventilation and/or respiratory insufficiency), intractable seizures, abnormal muscle tone and involuntary movements. Early death is usual.	Rare genetic neurological disorder
Orphanet:209886	OBSOLETE: Familial juvenile hyperuricemic nephropathy type 1	UMOD	1	NA	NA
Orphanet:209867	Autosomal dominant rhegmatogenous retinal detachment	COL2A1	1	A rare, hereditary, non-syndromic form of vitreoretinopathy characterized by retinal tears due to abnormal vitreous, and commonly present refractive errors. No other signs or symptoms of Stickler syndrome is present.	Rare genetic eye disease
Orphanet:210571	Dystonia 16	PRKRA	1	Dystonia 16 (DYT16) is a very rare and newly discovered movement disorder which is characterized by early-onset progressive limb dystonia, laryngeal and oromandibular dystonia, and parkinsonism.	Rare genetic neurological disorder
Orphanet:3286	Catecholaminergic polymorphic ventricular tachycardia	RYR2;CASQ2;TRDN;CALM1;CALM2;CALM3;TECRL	7	Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a severe genetic arrhythmogenic disorder characterized by adrenergically induced ventricular tachycardia (VT) manifesting as syncope and sudden death.	Rare genetic cardiac disease
Orphanet:210548	Macrocephaly-intellectual disability-autism syndrome	PTEN;HEPACAM	2	A rare, genetic, neurological disease characterized by association of macrocephaly, dysmorphic facial features and psychomotor delay leading to intellectual disability and autism spectrum disorder. Facial dysmorphism may include frontal bossing, hypertelorism, midface hypoplasia, depressed nasal bridge, short nose, and long philtrum.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:210159	Adult hepatocellular carcinoma	AXIN1;PIK3CA;CASP8;TP53;PDGFRL;CTNNB1;TSC2;TSC1;EGF	9	A rare neoplastic disease and the most common primary liver cancer of adulthood, characterized by hepatic mass, abdominal pain and, in advanced stages, jaundice, cachexia and liver failure. Derived from well-differentiated hepatocytes, it often develops from chronic liver cirrhosis which is most often due to hepatitis B and C virus or alcohol abuse.	
Orphanet:210163	Congenital lethal myopathy, Compton-North type	CNTN1	1	Congenital lethal myopathy, Compton-North type is a rare, genetic, lethal, non-dystrophic congenital myopathy disorder characterized, antenatally, by fetal akinesia, intrauterine growth restriction and polyhydramnios, and, following birth, by severe neonatal hypotonia, severe generalized skeletal, bulbar and respiratory muscle weakness, multiple flexion contractures, and normal creatine kinase serum levels. Ultrastructurally, loss of integrin alpha7, beta2-syntrophin and alpha-dystrobrevin from the muscle sarcolemma and disruption of sarcomeres with disorganization of the Z band are observed.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:210141	Inherited congenital spastic tetraplegia	KANK1;GAD1;ADD3	3	Inherited congenital spastic tetraplegia is a rare, genetic, neurological disease characterized by non-progressive, variable spastic quadriparesis in multiple members of a family, in the absence of additional factors complicating pregnancy or birth (e.g. perinatal asphyxia, congenital infection). Additional clinical features include congenital hypotonia, intellectual disability, and developmental delay. Dysphagia, dysarthria, exotropia, nystagmus, seizures and brain atrophy with ventriculomegaly may be also present.	
Orphanet:210144	Lethal polymalformative syndrome, Boissel type	FTO	1	Lethal polymalformative syndrome, Boissel type is a rare, genetic, lethal, multiple congenital anomalies/dysmorphic syndrome characterized by failure to thrive, severe developmental delay, severe postanatal microcephaly, frequent congenital cardiac defects and characteristic facial dysmorphysm (including coarse face with anteverted nostrils, thin vermillion, prominent alveolar ridge and retro- or micrognatia). Additional common features include neurologic abnormalities (hyper-/hypotonia, sensorineural deafness, hydrocephalus, cerebral atrophy, seizures), as well as brachydactyly, cutis marmorata and genital anomalies.	Rare genetic developmental defect during embryogenesis
Orphanet:1063	Tufted angioma	GNA14	1	A very rare, benign, cutaneous, slow-growing, vascular tumor mostly developing in infancy or early childhood.	Rare genetic developmental defect during embryogenesis
Orphanet:211067	Episodic ataxia type 5	CACNB4	1	Episodic ataxia type 5 (EA5) is an extremely rare form of Hereditary episodic ataxia (see this term) characterized by recurrent episodes of vertigo and ataxia lasting several hours.	Rare genetic neurological disorder
Orphanet:211017	Spinocerebellar ataxia type 30	SCA30	1	Spinocerebellar ataxia type 30 (SCA30) is a very rare subtype of autosomal dominant cerebellar ataxia type III (ADCA type III; see this term) characterized by a slowly progressive and relatively pure ataxia.	Rare genetic neurological disorder
Orphanet:2122	Kaposiform hemangioendothelioma	GNA14	1	A very rare, aggressive, vascular tumor manifesting in the neonatal period or in infancy as cutaneous vascular tumors to large infiltrative lesions.	
Orphanet:2591	Infantile myofibromatosis	NOTCH3;PDGFRB	2	A rare benign soft tissue tumor characterized by the development of nodules in the skin, striated muscles, bones, and in exceptional cases, visceral organs, leading to a broad spectrum of clinical symptoms. It contains myofibroblasts.	Rare genetic tumor
Orphanet:35	Propionic acidemia	PCCA;PCCB	2	Propionic acidemia (PA) is an organic aciduria caused by the deficient activity of the propionyl Coenzyme A carboxylase and is characterized by life threatening episodes of metabolic decompensation, neurological dysfunction and that may be complicated by cardiomyopathy.	Rare inborn errors of metabolism
Orphanet:663	Mitochondrial DNA-related progressive external ophthalmoplegia	MT-TS1;MT-TL2;MT-TN;MT-TL1	4	An Orphanet summary for this disease is currently under development. However, other data related to the disease are accessible from the Additional Information menu located on the right side of this page.	Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:220	Denys-Drash syndrome	WT1	1	A rare urogenital disorder characterized by the association of diffuse mesangial sclerosis (DMS), male pseudohermaphroditism with a 46,XY karyotype, and nephroblastoma.	Inherited cancer-predisposing syndrome;Rare genetic renal disease;Rare genetic gynecological and obstetrical diseases;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease
Orphanet:5	Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency	HADHA	1	A mitochondrial disorder of long chain fatty acid oxidation characterized in most patients by onset in infancy/ early childhood of hypoketotic hypoglycemia, metabolic acidosis, liver disease, hypotonia and, frequently, cardiac involvement with arrhythmias and/or cardiomyopathy.	Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic cardiac disease;Rare genetic endocrine disease;Rare inborn errors of metabolism
Orphanet:25	Glutaryl-CoA dehydrogenase deficiency	GCDH	1	Glutaryl-CoA dehydrogenase (GCDH) deficiency (GDD) is an autosomal recessive neurometabolic disorder clinically characterized by encephalopathic crises resulting in striatal injury and a severe dystonic dyskinetic movement disorder.	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:618	Familial melanoma	CDK4;CDKN2A;MITF;TERT;MC1R;BAP1;CDKN2B;CDKN2D;MGMT;POT1;ACD;TERF2IP	12	Familial melanoma (FM) is a rare inherited form of melanoma characterized by development of histologically confirmed melanoma in two first degrees relatives or more relatives in an affected family.	Rare genetic tumor
Orphanet:818	Smith-Lemli-Opitz syndrome	DHCR7	1	Smith-Lemli-Opitz syndrome (SLOS) is characterized by multiple congenital anomalies, intellectual deficit, and behavioral problems.	Rare genetic developmental defect during embryogenesis;Rare genetic renal disease;Rare genetic eye disease;Rare inborn errors of metabolism;Rare genetic bone disease;Rare genetic neurological disorder;Rare genetic urogenital disease;Rare genetic endocrine disease
Orphanet:213504	Adenocarcinoma of ovary	INHBA	1	NA	
Orphanet:175	Cartilage-hair hypoplasia	RMRP	1	Cartilage-hair hypoplasia is a disease affecting the bone metaphyses causing small stature from birth.	Rare genetic eye disease;Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic immune disease
Orphanet:42	Medium chain acyl-CoA dehydrogenase deficiency	ACADM	1	Medium chain acyl-CoA dehydrogenase (MCAD) deficiency (MCADD) is an inborn error of mitochondrial fatty acid oxidation characterized by a rapidly progressive metabolic crisis, often presenting as hypoketotic hypoglycemia, lethargy, vomiting, seizures and coma, which can be fatal in the absence of emergency medical intervention.	Rare inborn errors of metabolism
Orphanet:213524	Hereditary site-specific ovarian cancer syndrome	BRCA1;BRCA2	2	, confer an elevated ovarian cancer risk in a minority of patients.	Rare genetic tumor
Orphanet:2066	Gamma-aminobutyric acid transaminase deficiency	ABAT	1	Gamma-aminobutyric acid transaminase (GABA-T) deficiency is an extremely rare disorder of GABA metabolism characterized by a severe neonatal-infantile epileptic encephalopathy (manifesting with symptoms such as seizures, hypotonia, hyperreflexia and developmental delay) and growth acceleration.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:300	Bifunctional enzyme deficiency	HSD17B4;EHHADH	2	NA	Rare inborn errors of metabolism
Orphanet:860	Congenitally uncorrected transposition of the great arteries	MED13L;GDF1	2	Congenitally uncorrected transposition of the great arteries (congenitally uncorrected TGA), also referred to as complete transposition, is a congenital cardiac malformation characterized by atrioventricular concordance and ventriculoarterial (VA) discordance.	Rare genetic developmental defect during embryogenesis
Orphanet:213711	Endometrial stromal sarcoma	YWHAE;JAZF1;SUZ12;NUTM2A;NUTM2B	5	NA	
Orphanet:1572	Common variable immunodeficiency	CD19;ICOS;CR2;TNFRSF13C;MS4A1;CD81;PRKCD;TNFSF12;TNFSF12;NFKB1;NFKB2;TNFRSF13B	12	Common variable immunodeficiency (CVID) comprises a heterogeneous group of diseases characterized by a significant hypogammaglobulinemia of unknown cause, failure to produce specific antibodies after immunizations and susceptibility to bacterial infections, predominantly caused by encapsulated bacteria.	Rare genetic immune disease
Orphanet:3261	Autoimmune lymphoproliferative syndrome	CASP10;FAS;FAS;FASLG;PRKCD;RASGRP1	6	A rare, inherited disorder characterized by non-malignant lymphoproliferation, multilineage cytopenias, and a lifelong increased risk of Hodgkin's and non-Hodgkin's lymphoma.	Rare genetic immune disease;Inherited cancer-predisposing syndrome
Orphanet:2849	Perlman syndrome	DIS3L2	1	Perlman syndrome is characterized principally by polyhydramnios, neonatal macrosomia, bilateral renal tumours (hamartomas with or without nephroblastomatosis), hypertrophy of the islets of Langerhans and facial dysmorphism.	Rare genetic developmental defect during embryogenesis;Inherited cancer-predisposing syndrome
Orphanet:2953	Musculocontractural Ehlers-Danlos syndrome	P4HA1;CHST14;DSE	3	Ehlers-Danlos syndrome, musculocontractural type is a congenital form of Ehlers-Danlos syndrome characterized by distinct craniofacial features, multiple contractures, progressive joint and skin laxity, adduction-flexion contractures of the thumbs, talipes equinovarus, bruisability and multisystem fragility-related manifestations.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic systemic or rheumatologic disease;Rare inborn errors of metabolism;Rare genetic cardiac disease;Rare genetic neurological disorder;Rare genetic renal disease
Orphanet:782	Axenfeld-Rieger syndrome	PITX2;PITX2;FOXC1	3	Axenfeld-Rieger syndrome (ARS) is a generic term used to designate overlapping genetic disorders, in which the major physical condition is anterior segment dysgenesis of the eye. Patients with ARS may also present with multiple variable congenital anomalies.	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic endocrine disease
Orphanet:216718	Isolated congenitally uncorrected transposition of the great arteries	ZIC3;CFC1	2	NA	Rare genetic developmental defect during embryogenesis
Orphanet:216729	Congenitally uncorrected transposition of the great arteries with cardiac malformation	CFC1	1	NA	Rare genetic developmental defect during embryogenesis
Orphanet:882	Tyrosinemia type 1	FAH	1	Tyrosinemia type 1 (HTI) is an inborn error of tyrosine catabolism caused by defective activity of fumarylacetoacetate hydrolase (FAH) and is characterized by progressive liver disease, renal tubular dysfunction, porphyria-like crises and a dramatic improvement in prognosis following treatment with nitisinone.	Inherited cancer-predisposing syndrome;Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic hepatic disease;Rare genetic renal disease
Orphanet:216796	Osteogenesis imperfecta type 1	COL1A1;COL1A2	2	Osteogenesis imperfecta type I is a mild type of osteogenesis imperfecta (OI; see this term), a genetic disorder characterized by increased bone fragility, low bone mass and susceptibility to bone fractures.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease
Orphanet:216804	Osteogenesis imperfecta type 2	COL1A1;COL1A2;P3H1;CRTAP;PPIB	5	Osteogenesis imperfecta type II is a lethal type of osteogenesis imperfecta (OI; see this term), a genetic disorder characterized by increased bone fragility, low bone mass and susceptibility to bone fractures. Patients with type II present multiple rib and long bone fractures at birth, marked deformities, broad long bones, low density on skull X-rays, and dark sclera.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease
Orphanet:216812	Osteogenesis imperfecta type 3	COL1A1;COL1A2;P3H1;CRTAP;CREB3L1;PPIB;SERPINH1;FKBP10;SERPINF1;WNT1;BMP1	11	Osteogenesis imperfecta type III is a severe type of osteogenesis imperfecta (OI; see this term), a genetic disorder characterized by increased bone fragility, low bone mass and susceptibility to bone fractures. The main signs of type III include very short stature, a triangular face, severe scoliosis, grayish sclera, and dentinogenesis imperfecta (DI; see this term).	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease;Rare genetic odontologic disease
Orphanet:216820	Osteogenesis imperfecta type 4	TMEM38B;COL1A1;COL1A2;CRTAP;PPIB;FKBP10;SP7;SERPINF1;WNT1;SPARC	10	Osteogenesis imperfecta type IV is a moderate type of osteogenesis imperfecta (OI; see this term), a genetic disorder characterized by increased bone fragility, low bone mass and susceptibility to bone fractures. Patients with type IV have moderately short stature, mild to moderate scoliosis, grayish or white sclera, and dentinogenesis imperfecta (DI; see this term).	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease;Rare genetic odontologic disease
Orphanet:216828	Osteogenesis imperfecta type 5	IFITM5	1	Osteogenesis imperfecta type V is a moderate type of osteogenesis imperfecta (OI; see this term), a genetic disorder characterized by increased bone fragility, low bone mass and susceptibility to bone fractures with variable severity. OI type V is characterized by mild to moderate short stature, dislocation of the radial head, mineralized interosseous membranes, hyperplasic callus, white sclera and no dentinogenesis imperfecta (DI; see this term).	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:3474	CHIME syndrome	PIGL	1	CHIME syndrome is a rare ectodermal dysplasia syndrome characterized by ocular colobomas, cardiac defects, ichthyosiform dermatosis, intellectual disability, conductive hearing loss and epilepsy.	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic skin disease;Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic cardiac disease;Genetic otorhinolaryngologic disease
Orphanet:216866	Classic pantothenate kinase-associated neurodegeneration	PANK2	1	NA	Rare genetic eye disease;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:216873	Atypical pantothenate kinase-associated neurodegeneration	PANK2	1	NA	Rare genetic eye disease;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:216972	Niemann-Pick disease type C, severe perinatal form	NPC1;NPC2	2	NA	Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:216978	Niemann-Pick disease type C, late infantile neurologic onset	NPC1;NPC2	2	NA	Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:361	Familial glucocorticoid deficiency	STAR;MC2R;MRAP;TXNRD2;NNT	5	Familial glucocorticoid deficiency (FGD) is a group of primary adrenal insufficiencies characterized clinically by neonatal hyperpigmentation, hypoglycemia, failure to thrive, and recurrent infections, and biochemically by glucocorticoid deficiency without mineralocorticoid deficiency.	Rare genetic endocrine disease
Orphanet:216975	Niemann-Pick disease type C, severe early infantile neurologic onset	NPC1;NPC2	2	NA	Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:216986	Niemann-Pick disease type C, adult neurologic onset	NPC1;NPC2	2	NA	Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:216981	Niemann-Pick disease type C, juvenile neurologic onset	NPC1;NPC2	2	NA	Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:2088	Glycogen storage disease due to GLUT2 deficiency	SLC2A2	1	Fanconi-Bickel glycogenosis (FBG) is a rare glycogen storage disease characterized by hepatorenal glycogen accumulation, severe renal tubular dysfunction and impaired glucose and galactose metabolism.	Rare genetic hepatic disease;Rare inborn errors of metabolism;Rare genetic renal disease
Orphanet:217012	Spinocerebellar ataxia type 31	BEAN1	1	Spinocerebellar ataxia type 31 (SCA31) is a very rare subtype of autosomal dominant cerebellar ataxia type III (ADCA type III; see this term) characterized by the late-onset of cerebral ataxia, dysarthria and horizontal gaze nystagmus, and that is occasionally accompanied by pyramidal signs, tremor, decreased vibration sense and hearing difficulties.	Rare genetic neurological disorder
Orphanet:217023	OBSOLETE: Atypical hemolytic uremic syndrome with thrombomodulin anomaly	THBD	1	NA	NA
Orphanet:179	Birdshot chorioretinopathy	HLA-A	1	Birdshot chorioretinopathy is a posterior uveitis characterized by multiple cream-colored, hypopigmented choroidal lesions in the fundus and a strong association with HLA-A29 and clinically presenting with blurred vision, floaters, photopsia, scotoma and nyctalopia.	
Orphanet:217266	BNAR syndrome	FREM1	1	BNAR syndrome is a very rare multiple congenital anomaly syndrome characterized by a bifid nose (see this term) (with bulbous nasal tip but not associated with hypertelorism) with or without the presence of anal defects (i.e. anteriorly placed anus, rectal stenosis or atresia) and renal dysplasia (unilateral or bilateral renal agenesis, see these terms) and without intellectual disability. BNAR syndrome is phenotypically related to Fraser syndrome and oculotrichoanal syndrome (see these terms).	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Genetic otorhinolaryngologic disease
Orphanet:2584	Classic mycosis fungoides	CTLA4;TNFRSF1B;CD28	3	Classical mycosis fungoides is the most common type of mycosis fungoides (MF; see this term), a form of cutaneous T-cell lymphoma, and is characterized by slow progression from patches to more infiltrated plaques and eventually to tumors.	
Orphanet:217093	Mucopolysaccharidosis type 2, attenuated form	IDS	1	Mucopolysaccharidosis type 2, attenuated form (MPS2att), the less severe form of MPS2 (see this term), leads to a massive accumulation of glycosaminoglycans and a wide variety of symptoms including distinctive facies, short stature, cardiorespiratory and skeletal findings. It is differentiated from mucopolysaccharidosis type 2, severe form (see this term) by the absence of cognitive decline.	Rare genetic bone disease;Rare genetic cardiac disease;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic skin disease
Orphanet:3162	Sézary syndrome	CTLA4;TNFRSF1B;CD28	3	Sézary syndrome (SS) is an aggressive form of cutaneous T-cell lymphoma characterized by a triad of erythroderma, lymphadenopathy and circulating atypical lymphocytes (Sézary cells).	
Orphanet:217085	Mucopolysaccharidosis type 2, severe form	IDS	1	Mucopolysaccharidosis type 2 (MPS2, see this term), severe form (MPS2S), is associated with a massive accumulation of glycosaminoglycans and a wide variety of symptoms including a rapidly progressive cognitive decline; it is most often fatal in the second or third decade.	Rare genetic bone disease;Rare genetic cardiac disease;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic skin disease
Orphanet:217059	Isolated congenital digital clubbing	HPGD	1	Isolated congenital digital clubbing is a rare genodermatosis disorder characterized by enlargement of the terminal segments of fingers and toes with thickened nails without any other abnormality.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:1451	CINCA syndrome	NLRC4;NLRP3	2	Chronic Infantile Neurological, Cutaneous, and Articular (CINCA) syndrome is characterised by skin rash, joint involvement, chronic meningitis with granulocytes and, in some cases, sensorineural hearing loss and ocular signs.	Rare genetic systemic or rheumatologic disease;Rare genetic immune disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:217055	Autosomal recessive intermediate Charcot-Marie-Tooth disease type A	GDAP1	1	A subtype of autosomal recessive intermediate Charcot-Marie-Tooth (CMT) disease characterized by severe, early childhood-onset CMT neuropathy with prominent pes equinovarus deformity and impairment of hand muscles. Nerve conduction velocities usually range between 25-35 m/s and both axonal and demyelinating changes are observed on peripheral nerve pathology.	Rare genetic neurological disorder
Orphanet:217335	RIN2 syndrome	RIN2	1	RIN2 syndrome, formerly known as macrocephaly, alopecia, cutis laxa and scoliosis (MACS) syndrome, is a very rare inherited connective tissue disorder characterized by macrocephaly, sparse scalp hair, soft-redundant and hyperextensible skin, joint hypermobility, and scoliosis. Patients have progressive facial coarsening with downslanted palpebral fissures, upper eyelid fullness/infraorbital folds, thick/everted vermillion, gingival overgrowth and abnormal position of the teeth. Rarer manifestations such as abnormal high-pitched voice, bronchiectasis, hypergonadotropic hypergonadism and brachydactyly (see this term) have also been reported.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:217330	REN-related autosomal dominant tubulointerstitial kidney disease	REN	1	Familial juvenile hyperuricemic nephropathy type 2 is a rare autosomal dominantly inherited disease of childhood characterized by hypoproliferative anemia, hyperuricemia and slowly progressing kidney failure due to dysregulation of the renin-angiotensin system (RAS).	Rare genetic renal disease
Orphanet:1171	Cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome	ATP1A3	1	Cerebellar ataxia - areflexia - pes cavus - optic atrophy - sensorineural hearing loss (CAPOS syndrome) is a rare autosomal dominant neurological disorder characterized by early onset cerebellar ataxia, associated with areflexia, progressive optic atrophy, sensorineural deafness, a pes cavus deformity, and abnormal eye movements.	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:217566	Chronic respiratory distress with surfactant metabolism deficiency	SFTPC	1	Chronic respiratory distress with surfactant metabolism deficiency is a rare, genetic, primary interstitial lung disease with a highly variable clinical presentation, ranging from neonatal respiratory distress syndrome to mild to severe interstitial lung disease (typical symptoms include cough, tachypnea, hypoxia, clubbing, crackles, failure to thrive). Lung biopsy reveals diffuse alveolar damage, interstitial thickening with inflammatory infiltrates, fibroblast proliferation, collagen deposition, and multiple foci of fibrosis, alveolar type II cell hyperplasia, abundant foamy alveolar macrophages and granular lipoproteic material in the alveolar lumen. Imaging shows cystic spaces and ground-glass opacities that are typically homogenously diffuse.	Rare genetic respiratory disease
Orphanet:217563	Neonatal acute respiratory distress due to SP-B deficiency	SFTPB	1	NA	Rare genetic respiratory disease
Orphanet:1864	OBSOLETE: Congenital valvular dysplasia	FLNA	1	NA	NA
Orphanet:217407	Hereditary hypotrichosis with recurrent skin vesicles	DSC3	1	Hereditary hypotrichosis with recurrent skin vesicles is a very rare inherited hair loss disorder described in a family and characterized by sparse, fragile or absent hair on the scalp, eyebrows, eyelashes, axillae and rest of the body, associated with vesicle formation on various parts of the scalp and body which regularly burst and release watery fluid.	Rare genetic skin disease
Orphanet:217467	Hereditary thrombophilia due to congenital histidine-rich (poly-L) glycoprotein deficiency	HRG	1	Hereditary thrombophilia due to congenital histidine-rich (poly-L) glycoprotein deficiency is a rare, genetic, coagulation disorder characterized by a tendency to develop thrombosis, resulting from decreased histidine-rich glycoprotein (HRG) plasma levels. Manifestations are variable depending on location of thrombosis, but may include headaches, diplopia, progressive pain, limb swelling, itching or ulceration, and brownish skin discoloration, among others.	Rare genetic hematologic disease;Rare genetic bone disease
Orphanet:217390	Combined immunodeficiency due to DOCK8 deficiency	DOCK8	1	Combined immunodeficiency due to dedicator of cytokinesis 8 protein (DOCK8) deficiency is a form of T and B cell immunodeficiency characterized by recurrent cutaneous viral infections, susceptibility to cancer and elevated serum levels of immunoglobulin E (IgE).	Rare genetic immune disease
Orphanet:217385	17p13.3 microduplication syndrome	PAFAH1B1;YWHAE	2	17p13.3 microduplication syndrome is characterized by variable psychomotor delay and dysmorphic features.	Rare genetic developmental defect during embryogenesis;Rare chromosomal anomaly
Orphanet:217396	Progressive polyneuropathy with bilateral striatal necrosis	SLC25A19	1	Progressive polyneuropathy with bilateral striatal necrosis is a rare, genetic disorder of thiamine metabolism and transport characterized by the childhood-onset of recurrent episodes of flaccid paralysis and encephalopathy, associated with bilateral striatal necrosis and chronic progressive axonal polyneuropathy with proximal and distal muscle weakness, areflexia, contractures and foot deformities.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:217371	Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins	TRMU	1	A very rare mitochondrial respiratory chain deficiency characterized clinically by transient but life-threatening liver failure with elevated liver enzymes, jaundice, vomiting, coagulopathy, hyperbilirubinemia, and lactic acidemia.	Rare genetic hepatic disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:217382	Neurodegenerative syndrome due to cerebral folate transport deficiency	FOLR1	1	NA	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:217377	Microduplication Xp11.22p11.23 syndrome	IQSEC2	1	 recurrent Xp11.22-p11.23 microduplication has been recently identified in males and females.	Rare genetic developmental defect during embryogenesis;Rare chromosomal anomaly;Rare genetic neurological disorder
Orphanet:217622	Sensorineural deafness with dilated cardiomyopathy	EYA4	1	Sensorineural deafness with dilated cardiomyopathy is an extremely rare autosomal dominant syndrome described in two families to date and characterized by moderate to severe sensorineural hearing loss manifesting during childhood, and associated with late-onset dilated cardiomyopathy that generally progresses to heart failure.	Rare genetic cardiac disease
Orphanet:331	Congenital factor XIII deficiency	F13A1;F13B	2	Congenital factor XIII deficiency is an inherited bleeding disorder due to reduced levels and activity of factor XIII (FXIII) and characterized by hemorrhagic diathesis frequently associated with spontaneous abortions and defective wound healing. Factor XIII deficiency is one of the most rare coagulation factor deficiencies.	Rare genetic hematologic disease
Orphanet:159	Carnitine-acylcarnitine translocase deficiency	SLC25A20	1	Carnitine-acylcarnitine translocase (CACT) deficiency is a life-threatening, inherited disorder of fatty acid oxidation which usually presents in the neonatal period with severe hypoketotic hypoglycemia, hyperammonemia, cardiomyopathy and/or arrhythmia, hepatic dysfunction, skeletal muscle weakness, and encephalopathy.	Rare inborn errors of metabolism;Rare genetic cardiac disease
Orphanet:79	Congenital alpha2-antiplasmin deficiency	SERPINF2	1	Congenital alpha2 antiplasmin deficiency is a rare hemorrhagic disorder (see this term)caused by congenital deficiency of alpha2 antiplasmin, leading to dysregulated fibrinolysis and is characterized by a hemorrhagic tendency presenting from childhood with prolonged bleeding and ecchymoses following minor trauma and spontaneous bleeding episodes (often in unusual locations like diaphysis of long bones). Congenital alpha2 antiplasmin deficiency is inherited in an autosomal recessive manner.	Rare genetic hematologic disease;Serpinopathy
Orphanet:2157	Histidinemia	HAL	1	Histidinemia is a rare metabolic disorder characterized by elevated histidine levels in blood, urine, and cerebrospinal fluid, generally with no clinical repercussions.	Rare inborn errors of metabolism
Orphanet:220402	Limited cutaneous systemic sclerosis	CAV1;HLA-DRB1;CTGF;IRF5;KIAA0319L;CCR6	6	Limited cutaneous systemic sclerosis (lcSSc) is a subtype of systemic sclerosis (SSc; see this term) characterized by the association of Raynaud's phenomenon with skin fibrosis limited to the hands, face, feet and forearms.	
Orphanet:220407	Limited systemic sclerosis	HLA-DRB1	1	Limited systemic sclerosis (lSSc) (or SSc sine scleroderma) is a subset of systemic sclerosis (SSc; see this term) characterized by organ involvement in the absence of fibrosis of the skin.	
Orphanet:3124	Saccharopinuria	AASS	1	Saccharopinuria is a disorder of lysine metabolism associated with hyperlysinaemia and lysinuria.	Rare inborn errors of metabolism
Orphanet:220386	Semilobar holoprosencephaly	FGFR1;PTCH1;SHH;SIX3;TGIF1;ZIC2;GLI2;TDGF1;FOXH1;FGF8;DISP1;CDON;NODAL;DLL1;GAS1	15	Semilobar holoprosencephaly is one of the classical forms of holoprosencephaly (HPE; see this term) in which the left and right frontal and parietal lobes are fused and the interhemispheric fissure is only present posteriorly.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease
Orphanet:2203	Hyperlysinemia	AASS	1	Hyperlysinaemia is a lysine metabolism disorder characterised by elevated levels of lysine in the cerebrospinal fluid and blood. Variable degrees of saccharopinuria are also present.	Rare inborn errors of metabolism
Orphanet:220393	Diffuse cutaneous systemic sclerosis	CAV1;HLA-DRB1;CTGF;IRF5;CCR6	5	Diffuse cutaneous systemic sclerosis (dcSSc) is a subtype of Systemic Sclerosis (SSc; see this term) characterized by truncal and acral skin fibrosis with an early and significant incidence of diffuse involvement (interstitial lung disease, oliguric renal failure, diffuse gastrointestinal disease, and myocardial involvement).	
Orphanet:332	Congenital intrinsic factor deficiency	GIF	1	Congenital intrinsic factor deficiency (IFD) is a rare disorder of vitamin B12 (cobalamin) absorption that is characterized by megaloblastic anemia and neurological abnormalities.	Rare inborn errors of metabolism;Rare genetic hematologic disease
Orphanet:220436	Quebec platelet disorder	PLAU	1	Quebec platelet syndrome (QPS) is a platelet granule disorder characterized by moderate to severe bleeding after trauma, surgery or obstetric interventions, frequent ecchymoses, mucocutaneous bleeding and muscle and joint bleeds.	Rare genetic hematologic disease
Orphanet:2195	Dicarboxylic aminoaciduria	SLC1A1	1	Dicarboxylicaminoaciduria is characterised by infantile-onset hypoglycaemia and hyperprolinaemia associated, in certain cases, with intellectual deficit.	Rare inborn errors of metabolism
Orphanet:220443	Bleeding diathesis due to thromboxane synthesis deficiency	TBXA2R	1	Bleeding diathesis due to thromboxane synthesis deficiency is a rare, genetic, isolated constitutional thrombocytopenia disease characterized by impaired platelet aggregation resulting from a defect in thromboxane synthesis or signaling, manifesting with mild to moderate mucocutaneous, gastrointestinal or surgical bleeding (e.g. easy bruising, prolonged epistaxis, excessive bleeding after a tooth extraction).	Rare genetic hematologic disease
Orphanet:2170	Methylcobalamin deficiency type cblG	MTR	1	NA	Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic hematologic disease
Orphanet:220295	Xeroderma pigmentosum-Cockayne syndrome complex	ERCC5;ERCC4;ERCC2;ERCC3	4	Xeroderma pigmentosum/Cockayne syndrome complex (XP/CS complex) is characterized by the cutaneous features of xeroderma pigmentosum (XP) (see this term) together with the systemic and neurological features of Cockayne syndrome (CS; see this term).	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder;Inherited cancer-predisposing syndrome;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic skin disease
Orphanet:414	Gyrate atrophy of choroid and retina	OAT	1	Gyrate atrophy of the choroid and retina (GACR) is a very rare, inherited retinal dystrophy, characterized by progressive chorioretinal atrophy, myopia and early cataract.	Rare genetic neurological disorder;Rare genetic eye disease;Rare inborn errors of metabolism
Orphanet:927	Hyperammonemia due to N-acetylglutamate synthase deficiency	NAGS	1	N-acetylglutamate synthase (NAGS) deficiency is a urea cycle disorder leading to hyperammonaemia.	Rare inborn errors of metabolism
Orphanet:2880	Phosphoenolpyruvate carboxykinase deficiency	PCK1;PCK2	2	Phosphoenolpyruvate carboxykinase (PEPCK) deficiency is a gluconeogenesis disorder that results from impairment in the enzyme PEPCK, and comprising cytosolic (PEPCK1) and mitochondrial (PEPCK2) forms of enzyme deficiency. Onset of symptoms is neonatal or a few months after birth and includes hypoglycemia associated with acute episodes of severe lactic acidosis, progressive neurological deterioration, severe liver failure, renal tubular acidosis and Fanconi syndrome. Patients also present progressive multisystem damage with failure to thrive, muscular weakness and hypotonia, developmental delay with seizures, spasticity, lethargy, microcephaly and cardiomyopathy. To date, there is no conclusive evidence of the existence of an isolated form of this disorder.	Rare inborn errors of metabolism
Orphanet:220465	Laron syndrome with immunodeficiency	STAT5B	1	This syndrome is characterized by severe growth retardation associated with immunodeficiency.	Rare genetic immune disease;Rare genetic gastroenterological disease;Rare genetic endocrine disease
Orphanet:941	D-glyceric aciduria	GLYCTK	1	 gene has been mapped to 3p21.	Rare inborn errors of metabolism
Orphanet:2843	Pentosuria	DCXR	1	Pentosuria is an inborn error of metabolism which is characterized by the excretion of 1 to 4 g of the pentose L-xylulose in the urine per day.	Rare inborn errors of metabolism
Orphanet:220497	Joubert syndrome with renal defect	NPHP1;RPGRIP1L;TMEM237	3	Joubert syndrome with renal defect is a rare subtype of Joubert syndrome and related disorders (JSRD, see this term) characterized by the neurological features of JS associated with renal disease, in the absence of retinopathy.	Rare genetic renal disease;Ciliopathy;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:220493	Joubert syndrome with ocular defect	AHI1;MKS1;INPP5E;CEP41;CEP120	5	Joubert syndrome with ocular defect is, along with pure JS, the most frequent subtype of Joubert syndrome and related disorders (JSRD, see these terms) characterized by the neurological features of JS associated with retinal dystrophy.	Rare genetic eye disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Ciliopathy
Orphanet:212	Cystathioninuria	CTH	1	Cystathioninuria is an autosomal recessive disorder caused by cystathionine gamma-lyase deficiency. It is usually pyridoxine-dependent, but in very rare cases it may be non-dependent. It is generally considered to be a benign condition without pathogenic relevance. However, association of cystathioninuria with intellectual impairment has been reported in several cases.	Rare inborn errors of metabolism
Orphanet:470	Lysinuric protein intolerance	SLC7A7	1	Lysinuric protein intolerance (LPI) is a very rare inherited multisystem condition caused by distrubance in amino acid metabolism.	Rare inborn errors of metabolism
Orphanet:145	Hereditary breast and ovarian cancer syndrome	PTEN;RAD51;BRCA1;BRCA2;BRIP1;CHEK2;TP53;MRE11;NBN;PALB2;BARD1;RAD51C;RAD50;RAD51D	14	Breast cancer (BC) is the most common cancer in women, accounting for 25% of all new cases of cancer. Most BC cases are sporadic, while 5-10% are estimated to be due to an inherited predisposition.	Rare genetic tumor
Orphanet:2965	Prolactinoma	CDH23;MEN1;AIP	3	Prolactinoma is a usually benign neoplasm of the pituitary gland that results in hyperprolactinemia. The most common clinical manifestations are amenorrhea and infertility in women; and impotence, decreased libido and infertility in men.	Rare genetic endocrine disease
Orphanet:538	Lymphangioleiomyomatosis	TSC1;TSC2	2	Lymphangioleiomyomatosis (LAM) is a multiple cystic lung disease characterized by progressive cystic destruction of the lung and lymphatic abnormalities, frequently associated with renal angiomyolipomas (AMLs). LAM occurs either sporadically or as a manifestation of tuberous sclerosis complex (TSC).	
Orphanet:1578	Pterin-4 alpha-carbinolamine dehydratase deficiency	PCBD1	1	Dehydratase deficiency or pterin-4 alpha-carbinolamine dehydratase (PCD) is considered a transient and benign form of hyperphenylalaninemia due to tetrahydrobiopterin deficiency (see this term), characterized by muscular hypotonia, irritability (detected by EEG), slow acquisition of psychomotor skills, age-dependent movement disorders, including dystonia and an accompanying excretion of 7-substituted pterins. Neurological developement is normal with dietary control of blood phenyalanine. PCD is inherited in an autosomal recessive manner.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:3208	Isolated succinate-CoQ reductase deficiency	SDHA;SDHB;SDHD;SDHAF1	4	A rare, mitochondrial oxidative phosphorylation disorder characterized by a highly variable phenotype. The severe, multisystemic disease involves brain, heart, muscles, liver, kidneys, and eyes and results in death in infancy. Mildly affected individuals have only isolated cardiac or muscle involvement in the adulthood. Histochemical and biochemical analysis reveals a global reduction of succinate dehydrogenase activity.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:24	Fumaric aciduria	FH	1	Fumaric aciduria (FA), an autosomal recessive metabolic disorder, is most often characterized by early onset but non-specific clinical signs: hypotonia, severe psychomotor impairment, convulsions, respiratory distress, feeding difficulties and frequent cerebral malformations, along with a distinctive facies. Some patients present with only moderate intellectual impairment.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:1561	Fatal infantile cytochrome C oxidase deficiency	SCO1;SCO2;COX15;COA5;COA6	5	Fatal infantile cytochrome C oxidase deficiency is a very rare mitochondrial disease characterized clinically by cardioencephalomyopathy resulting in death in infancy.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:221016	Rothmund-Thomson syndrome type 2	RECQL4	1	Rothmund-Thomson syndrome type 2 is a subform of Rothmund-Thomson syndrome (RTS; see this term) presenting with a characteristic facial rash (poikiloderma) and frequently associated with short stature, sparse scalp hair, sparse or absent eyelashes and/or eyebrows, congenital bone defects and an increased risk of osteosarcoma in childhood and squamous cell carcinoma later in life.	Inherited cancer-predisposing syndrome;Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:1460	Isolated complex III deficiency	BCS1L;MT-CYB;UQCRQ;UQCRB;TTC19;UQCRC2;CYC1;LYRM7;UQCC2;UQCC3	10	Isolated complex III deficiency is a rare, genetic, mitochondrial oxidative phosphorylation disorder characterized by a wide spectrum of clinical manifestations ranging from isolated myopathy or transient hepatopathy to severe multisystem disorder (that may include hypotonia, failure to thrive, psychomotor delay, cardiomyopathy, encephalopathy, renal tubulopathy, hearing impairment, lactic acidosis, hypoglycemia and other signs and symptoms).	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:851	Paris-Trousseau thrombocytopenia	FLI1	1	Paris-Trousseau thrombocytopenia (TCPT) is a contiguous gene syndrome characterized by mild bleeding tendency, variable thrombocytopenia (THC), dysmorphic facies, abnormal giant alpha-granules in platelets and dysmegakaryopoiesis.	Rare chromosomal anomaly;Rare genetic hematologic disease
Orphanet:221043	Hereditary fibrosing poikiloderma-tendon contractures-myopathy-pulmonary fibrosis syndrome	FAM111B	1	Hereditary fibrosing poikiloderma-tendon contractures-myopathy-pulmonary fibrosis syndrome is a rare, genetic, hereditary poikiloderma syndrome characterized by early-onset poikiloderma (mainly on the face), hypotrichosis, hypohidrosis, muscle and tendon contractures with varus foot deformity, progressive proximal and distal muscle weakness in all extremities, and progressive pulmonary fibrosis. Mild lymphedema of the extremities, growth retardation, liver impairment, exocrine pancreatic insufficiency and hematologic abnormalities are additional variable features.	Rare genetic neurological disorder;Rare genetic respiratory disease;Rare genetic skin disease
Orphanet:221046	Poikiloderma with neutropenia	USB1	1	Poikiloderma with neutropenia is a rare, genetic hereditary poikiloderma disorder characterized by early-onset poikiloderma (which typically begins in the extremities, progresses centripetally and eventually involves the trunk, face and ears) associated with chronic neutropenia, recurrent infections, pachyonychia and palmoplantar keratoderma. Growth and/or develomental delay and hepato- and/or splenomegaly are additional reported features.	Rare genetic immune disease;Rare genetic skin disease
Orphanet:745	Severe hereditary thrombophilia due to congenital protein C deficiency	PROC	1	Congenital protein C deficiency is an inherited coagulation disorder characterized by deep venous thrombosis symptoms due to reduced synthesis and/or activity levels of protein C.	Rare genetic hematologic disease;Rare genetic bone disease
Orphanet:849	Glanzmann thrombasthenia	ITGA2B;ITGB3	2	Glanzmann thrombasthenia (GT) is a bleeding syndrome characterized by spontaneous mucocutaneous bleeding and an exaggerated response to trauma due to a constitutional thrombocytopenia.	Rare genetic hematologic disease
Orphanet:221061	Familial cerebral cavernous malformation	CCM2;KRIT1;PDCD10	3	A rare, capillary-venous malformations characterized by closely clustered irregular dilated capillaries that can be asymptomatic or that can cause variable neurological manifestations such as seizures, non-specific headaches, progressive or transient focal neurologic deficits, and/or cerebral hemorrhages.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:225154	Familial infantile bilateral striatal necrosis	ADAR;MT-ATP6;NUP62	3	Familial infantile bilateral striatal necrosis is the familial form of infantile bilateral striatal necrosis (IBSN; see this term), a syndrome of bilateral symmetric spongy degeneration of the caudate nucleaus, putamen and globus pallidus characterized by developmental regression, choreoathetosis and dystonia progressing to spastic quadriparesis.	Rare genetic neurological disorder
Orphanet:225123	Hemochromatosis type 3	TFR2	1	Type 3 hemochromatosis is a form of rare hereditary hemochromatosis (HH) (see this term), a group of diseases characterized by excessive tissue iron deposition of genetic origin.	Rare genetic hepatic disease;Rare inborn errors of metabolism
Orphanet:221126	Fowler vasculopaty	FLVCR2	1	A rare, genetic neurological disorder characterized by hydranencephaly, distinctive glomeruloid vasculopathy in the central nervous system and retina, polyhydramnios and fetal akinesia with arthrogryposis. The disorder is usually prenatally lethal. In rare reported cases that survived beyond infancy, severe intellectual and neurologic disability with seizures, microcephaly and absence of functional movements were reported.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:221139	Combined immunodeficiency with faciooculoskeletal anomalies	KNSTRN;PIK3CD	2	Combined immunodeficiency with faciooculoskeletal anomalies is an extremely rare combined immunodeficiency disorder characterized by primary immunodeficiency manifesting with repeated bacterial, viral and fungal infections, in association with neurological manifestations (hypotonia, cerebellar ataxia, myoclonic seizures), developmental delay, optic atrophy, facial dysmorphism (high forehead, hypoplastic supraorbital ridges, palpebral edema, hypertelorism, flat nasal bridge, broad nasal root and tip, anteverted nares, thin lower lip overlapped by upper lip, square chin) and skeletal anomalies (short metacarpals/metatarsals with cone-shaped epiphyses, osteopenia).	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic immune disease
Orphanet:221145	Cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies	LTBP4;LTBP4	2	A rare, genetic, dermis elastic tissue disorder characterized by generalized cutis laxa associated with severe, usually early-onset, pulmonary emphysema, frequent and severe gastrointestinal and genitourinary involvement (i.e. bladder/intestine diverticula and/or tortuosity, gastrointestinal fragility, hydronephrosis), and mild cardiovascular involvement (typically limited to peripheral pulmonary artery stenosis only).	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:221150	Pitt-Hopkins-like syndrome	CNTNAP2;NRXN1	2	Pitt-Hopkins-like syndrome is a rare, genetic, syndromic intellectual disability disorder characterized by severe intellectual disability, lack of speech with normal, or mildly delayed, motor development, episodic breathing abnormalities, early-onset seizures and facial dysmorphism which only includes a wide mouth. Abnormal sleep-wake cycles, autistic behavior and stereotypic movements are commonly associated.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:228003	Severe combined immunodeficiency due to CORO1A deficiency	CORO1A	1	NA	Rare genetic immune disease
Orphanet:228000	Idiopathic CD4 lymphocytopenia	UNC119	1	Idiopathic CD4 lymphocytopenia is a rare primary immunodeficiency disorder characterized by persistent CD4 T-cell lymphopenia (less than 300 cells/µL on multiple occasions) not associated with any other underlying primary or secondary immune deficiency. Patients typically present opportunistic infections (with cryptococcal, mycobacterial, candidal, varicella zoster virus infections and progressive multifocal leukoencephalopathy being the most prevalent), malignancies (mainly lymphoproliferative disorders), or autoimmune disorders. Some individuals are asymptomatic and incidentally diagnosed.	Rare genetic immune disease
Orphanet:842	Testicular seminomatous germ cell tumor	KIT	1	Testicular seminomatous germ cell tumor is a rare testicular germ cell tumor (see this term), most commonly presenting with a painless mass in the scrotum, with a very high cure rate if caught in the early stages.	
Orphanet:227976	Autosomal recessive optic atrophy, OPA7 type	TMEM126A	1	A rare, syndromic, hereditary optic neuropathy disorder characterized by early-onset, severe, progressive visual impairment, optic disc pallor and central scotoma, variably associated with dyschromatopsia, auditory neuropathy (e.g. mild progressive sensorineural hearing loss), sensorimotor axonal neuropathy and, occasionally, moderate hypertrophic cardiomyopathy.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:227796	Fundus albipunctatus	PRPH2;RDH5;RLBP1	3	Fundus albipunctatus is a rare, genetic retinal dystrophy disorder characterized by the presence of numerous small, round, yellowish-white retinal lesions that are distributed throughout the retina but spare the fovea. Patients present in childhood with non-progressive night blindness with prolonged cone and rod adaptation times. The macula may or may not be involved, which may result in a decrease of central visual acuity with age.	Rare genetic eye disease
Orphanet:228012	Progressive sensorineural hearing loss-hypertrophic cardiomyopathy syndrome	MYO6	1	Progressive sensorineural hearing loss - hypertrophic cardiomyopathy is an extremely rare disorder described in one family to date that is characterized by progressive, late onset, autosomal dominant sensorineural hearing loss, QT interval prolongation, and mild cardiac hypertrophy.	Genetic otorhinolaryngologic disease;Rare genetic cardiac disease
Orphanet:543	Burkitt lymphoma	MYC	1	Burkitt lymphoma is a rare form of malignant mature B-cell non-Hodgkin lymphoma.	
Orphanet:319	Ewing sarcoma	ERG;ETV1;EWSR1;FLI1;ETV4	5	Ewing's sarcoma is a malignant small round cell bone tumor with strong metastatic potential.	
Orphanet:227535	Hereditary breast cancer	BRCA1;BRCA2;PALB2;XRCC2;KLLN;RAD54L;PPM1D;SLC22A18	8	NA	Rare genetic tumor
Orphanet:668	Osteosarcoma	CHEK2;RB1;TP53;TP53	4	Osteosarcoma is a primary malignant tumour of the skeleton characterised by the direct formation of immature bone or osteoid tissue by the tumour cells.	
Orphanet:227510	Multiple system atrophy, cerebellar type	COQ2	1	Multiple system atrophy, cerebellar type (MSA-c) is a form of multiple system atrophy (MSA; see this term) with predominant cerebellar features (gait and limb ataxia, oculomotor dysfunction, and dysarthria).	
Orphanet:2030	Fibrosarcoma	ETV6;NTRK3	2	NA	
Orphanet:2126	Solitary fibrous tumour/hemangiopericytoma	STAT6;NAB2	2	Solitary fibrous tumor (SFT) represents a diverse group of ubiquitous rare spindle cell neoplasms that may be benign or malignant and that most frequently arises from the pleura and peritoneum and rarely from other sites such as head and neck, liver and skeletal muscle. SFT may be clinically asymptomatic or may present with enlarging mass, compressive effects depending on the site involved and rarely with paraneoplastic manifestations (osteoarthropathy or hypoglycemia).	
Orphanet:758	Pseudoxanthoma elasticum	ABCC6;ENPP1	2	Pseudoxanthoma elasticum (PXE) is an inherited connective tissue disorder characterized by progressive calcification and fragmentation of elastic fibers in the skin, retina, and arterial walls.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic eye disease;Rare genetic neurological disorder;Rare genetic renal disease;Rare genetic cardiac disease
Orphanet:419	Hyperprolinemia type 1	PRODH	1	, 22q11.2).	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:1501	Adrenocortical carcinoma	TP53	1	A rare cancer that arises from the adrenal cortex.	
Orphanet:226316	Genetic transient congenital hypothyroidism	DUOX2	1	Genetic transient congenital hypothyroidism is a rare, thyroid disease characterized by a gene mutation induced, temporary deficiency of thyroid hormones at birth, which later reverts to normal with or without replacement therapy in the first few months or years of life.	Rare genetic endocrine disease
Orphanet:226307	Hypothyroidism due to deficient transcription factors involved in pituitary development or function	POU1F1;PROP1;HESX1;LHX3;LHX4	5	Hypothyroidism due to mutations in transcription factors involved in pituitary development or function is a type of central congenital hypothyroidism (see this term), a permanent thyroid deficiency that is present from birth, characterized by low levels of thyroid hormones caused by disorders in the development or function of the pituitary.	Rare genetic endocrine disease
Orphanet:3148	Malignant peripheral nerve sheath tumor	SH3PXD2A;HTRA1	2	Malignant peripheral nerve sheath tumor (MPNST) is a rare and often aggressive soft tissue sarcoma occurring in a wide range of anatomical sites.	
Orphanet:3273	Synovial sarcoma	SS18;SSX1;SSX2	3	Synovial sarcoma is an aggressive soft tissue sarcoma (see this term), occurring most commonly in adolescents and young adults (15 to 40 years), usually localized near the large joints of the extremities but also in the head and neck, mediastinum and viscera (lung, kidney etc), clinically presenting as a deep seated swelling or a painful mass often with an initial indolent course and is characterized by its local invasiveness and a propensity to metastasize. The origin of synovial sarcoma is likely from multipotent mesenchymal cells and not synovium (contrary to its name).	
Orphanet:503	Larsen syndrome	FLNB	1	An orofacial clefting syndrome characterized by congenital dislocation of large joints, foot deformities, cervical spine dysplasia, scoliosis, spatula-shaped distal phalanges and distinctive craniofacial abnormalities, including cleft palate.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:2542	Isolated microphthalmia-anophthalmia-coloboma	SIX6;SOX2;OTX2;VSX2;RAX;ALDH1A3;GDF3	7	A non-syndromic group of structural developmental eye defects characterized by the variable combination of microphthalmia, ocular coloboma, and anophthalmia, either unilaterally or bilaterally, with no other associated ocular conditions in the affected/contralateral eye, and no systemic anomalies.	NA
Orphanet:2478	Megalencephalic leukoencephalopathy with subcortical cysts	MLC1;HEPACAM	2	Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a form of leukodystrophy that is characterized by infantile-onset macrocephaly, often with mild neurologic signs at presentation (such as mild motor delay), which worsen with time, leading to poor ambulation, falls, ataxia, spasticity, increasing seizures and cognitive decline. Brain magnetic resonance imaging reveals diffusely abnormal and mildly swollen white matter as well as subcortical cysts in the anterior temporal and frontoparietal regions.	Rare genetic neurological disorder
Orphanet:3337	Primary Fanconi syndrome	EHHADH;SLC34A1	2	NA	Rare genetic renal disease
Orphanet:223	Nephrogenic diabetes insipidus	AVPR2;AQP2	2	Nephrogenic diabetes insipidus (NDI) is characterized by polyuria with polydipsia, recurrent bouts of fever, constipation, and acute hypernatremic dehydration after birth that may cause neurological sequelae. Polyuria may exceed 10 litres in children.	Rare genetic renal disease
Orphanet:228423	Monocytopenia with susceptibility to infections	GATA2	1	Monocytopenia with susceptibility to infections is a rare, genetic, primary immunodeficiency disorder characterized by profound circulating monocytopenia, B- and NK-cell lymphopenia and severe dentritic cell decrease, which manifests clinically with disseminated mycobacterial and viral infections, as well as opportunistic fungal and parasitic infections and frequent pulmonary alveolar proteinosis. Predisposition to developping myeloid neoplasms is associated.	Rare genetic immune disease
Orphanet:521	Chronic myeloid leukemia	BCR;ABL1;RUNX1	3	Chronic myeloid leukaemia (CML) is the most common myeloproliferative disorder accounting for 15-20% of all leukaemia cases.	
Orphanet:228415	5q35 microduplication syndrome	NSD1	1	The newly described 5q35 microduplication syndrome is associated with microcephaly, short stature, developmental delay and delayed bone maturation.	Rare chromosomal anomaly
Orphanet:132	Butyrylcholinesterase deficiency	BCHE	1	Butyrylcholinesterase (BChE) deficiency is a metabolic disorder characterised by prolonged apnoea after the use of certain anaesthetic drugs, including the muscle relaxants succinylcholine or mivacurium and other ester local anaesthetics. The duration of the prolonged apnoea varies significantly depending on the extent of the enzyme deficiency.	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:228426	Syndromic multisystem autoimmune disease due to Itch deficiency	ITCH	1	Syndromic multisystem autoimmune disease due to Itch deficiency is a rare, genetic, systemic autoimmune disease characterized by failure to thrive, global developmental delay, distictive craniofacial dysmorphism (relative macrocephaly, dolichocephaly, frontal bossing, orbital proptosis, flattened midface with a prominent occiput, low, posteriorly rotated ears, micrognatia), hepato- and/or splenomegaly, and multisystemic autoimmune disease involving the lungs, liver, gut and/or thyroid gland.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic immune disease;Rare genetic gastroenterological disease
Orphanet:2345	Isolated Klippel-Feil syndrome	GDF3;MEOX1;GDF6	3	Klippel-Feil Syndrome is characterised by improper segmentation of cervical segments resulting in congenitally fused cervical vertebrae.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:1333	Familial pancreatic carcinoma	BRCA1;BRCA2;CDKN2A;SMAD4;TP53;KRAS;PALB2;PALLD	8	Familial pancreatic carcinoma is defined by the presence of pancreatic cancer (PC) in two or more first-degree relatives.	Rare genetic gastroenterological disease
Orphanet:228387	Spondylo-megaepiphyseal-metaphyseal dysplasia	NKX3-2	1	Spondylo-megaepiphyseal-metaphyseal dysplasia is a rare, genetic primary bone displasia characterized by disproportionate short stature with short, stiff neck and trunk and relatively long limbs, fingers and toes (which may present flexion contractures), severe vertebral body ossification delay (with frequent kyknodysostosis), markedly enlarged round epiphyses of the long bones, absent ossification of pubic bones and multiple pseudoepiphyses of the short tubular bones in hands and feet. Neurological manifestations resulting from cervical spine instability may be observed.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:228390	Frontonasal dysplasia-alopecia-genital anomalies syndrome	ALX4	1	Frontonasal dysplasia with alopecia and genital anomaly is a new phenotype of frontonasal dysplasia associated with total alopecia and hypogonadism.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic skin disease
Orphanet:228410	Polyvalvular heart disease syndrome	TAB2;TAB2	2	Polyvalvular heart disease syndrome is a recently described syndrome characterized by the combination of polyvalvular heart disease, short stature, facial anomalies and intellectual deficit.	Rare genetic developmental defect during embryogenesis;Rare genetic cardiac disease
Orphanet:228402	2q23.1 microdeletion syndrome	MBD5	1	The newly described 2q23.1 microdeletion syndrome includes severe intellectual deficit with pronounced speech delay, behavioral abnormalities including hyperactivity and inappropriate laughter, short stature and seizures.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare chromosomal anomaly
Orphanet:228366	CLN7 disease	MFSD8	1	NA	Rare genetic eye disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:228363	CLN6 disease	CLN6	1	NA	Rare genetic eye disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:228360	CLN5 disease	CLN5	1	NA	Rare genetic eye disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:228384	5q14.3 microdeletion syndrome	MEF2C	1	The newly described 5q14.3 microdeletion syndrome includes severe intellectual deficit with no speech, stereotypic movements and epilepsy.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare chromosomal anomaly
Orphanet:228374	Charcot-Marie-Tooth disease type 2B5	NEFL	1	A rare axonal hereditary motor and sensory neuropathy characterized by infantile onset of slowly progressive distal motor weakness and atrophy (more severe in legs and moderate in arms) with mildly delayed motor development, hypotonia, and distal sensory impairment of all sensory modalities.	Rare genetic neurological disorder
Orphanet:228340	CLN4A disease	CLN6	1	NA	Rare genetic eye disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:228337	CLN10 disease	CTSD	1	NA	Rare genetic eye disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:228329	CLN1 disease	PPT1	1	NA	Rare genetic eye disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:228354	CLN8 disease	CLN8	1	NA	Rare genetic eye disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:228349	CLN2 disease	TPP1	1	NA	Rare genetic eye disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:228346	CLN3 disease	CLN3	1	NA	Rare genetic eye disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:228343	CLN4B disease	DNAJC5	1	NA	Rare genetic eye disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:228302	Carnitine palmitoyl transferase II deficiency, myopathic form	CPT2	1	The myopathic form of carnitine palmitoyltransferase II (CPT II) deficiency, an inherited metabolic disorder that affects mitochondrial oxidation of long chain fatty acids (LCFA), is the most common and the least severe form of CPT II deficiency (see this term).	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:228305	Carnitine palmitoyl transferase II deficiency, severe infantile form	CPT2	1	The severe infantile form of carnitine palmitoyltransferase II (CPT II) deficiency (see this term), an inherited disorder that affects mitochondrial oxidation of long chain fatty acids (LCFA), is the early-onset form of the disease.	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:228308	Carnitine palmitoyl transferase II deficiency, neonatal form	CPT2	1	The neonatal form of carnitine palmitoyltransferase II (CPT II) deficiency (see this term), an inherited disorder that affects mitochondrial oxidation of long chain fatty acids (LCFA), is the lethal form of the disease which presents with multisystem failure.	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:3203	Overhydrated hereditary stomatocytosis	RHAG	1	Overhydrated hereditary stomatocytosis (OHSt) is a disorder of red cell membrane permeability to monovalent cations and is characterized clinically by hemolytic anemia.	Rare genetic hematologic disease
Orphanet:3202	Dehydrated hereditary stomatocytosis	SLC4A1;PIEZO1;KCNN4	3	Dehydrated hereditary stomatocytosis (DHS) is a rare hemolytic anemia characterized by a decreased red cell osmotic fragility due to a defect in cation permeability, resulting in red cell dehydration and mild to moderate compensated hemolysis. Pseudohyperkalemia (loss of potassium ions from red cells on storage at room temperature) is sometimes observed.	Rare genetic hematologic disease
Orphanet:228140	Idiopathic ventricular fibrillation, non Brugada type	SCN5A;DPP6	2	A rare, genetic, cardiac rhythm disease characterized by ventricular fibrillation in the absence of any structural or functional heart disease, or known repolarization abnormalities. The presence of J waves is associated with a higher risk of nocturnal ventricular fibrillation events and a higher risk of recurrence.	Rare genetic cardiac disease
Orphanet:1018	X-linked Alport syndrome-diffuse leiomyomatosis	COL4A6;COL4A5	2	The association of X-linked Alport syndrome with leiomyomatosis of the esophagus, tracheobronchial tree or female genitals has been reported in more than 30 families.	Genetic otorhinolaryngologic disease;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare chromosomal anomaly;Rare genetic renal disease
Orphanet:306	Benign familial infantile epilepsy	SCN8A;SCN2A;KCNQ2;KCNQ3;PRRT2	5	Benign familial infantile epilepsy (BFIE) is a genetic epileptic syndrome characterized by the occurrence of afebrile repeated seizures in healthy infants, between the third and eighth month of life.	Rare genetic neurological disorder
Orphanet:228174	Autosomal dominant Charcot-Marie-Tooth disease type 2N	AARS	1	A mild form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy, characterized by distal legs sensory loss and weakness that can be asymmetric. Tendon reflexes are reduced in the knees and absent in ankles. Progression is slow.	Rare genetic neurological disorder
Orphanet:328	Congenital factor X deficiency	F10	1	Congenital factor X deficiency is an inherited bleeding disorder with a decreased antigen and/or activity of factor X (FX) and characterized by mild to severe bleeding symptoms.	Rare genetic hematologic disease
Orphanet:228169	Autosomal dominant striatal neurodegeneration	PDE8B	1	An adult-onset movement disorder characterized by bradykinesia, dysarthria and muscle rigidity.	Rare genetic neurological disorder
Orphanet:2132	Hemoglobin C disease	HBB	1	Hemoglobin C disease (HbC) is a hemoglobinopathy characterized by production of abnormal variant hemoglobin known as hemoglobin C, with no or mild clinical manifestations (hemolytic anemia).	Rare genetic hematologic disease
Orphanet:2133	Hemoglobin E disease	HBB	1	Hemoglobin E disease (HbE) is a hemoglobinopathy characterized by production of abnormal variant hemoglobin known as hemoglobin E, with a generally benign, asymptomatic presentation.	Rare genetic hematologic disease
Orphanet:288	Hereditary elliptocytosis	SPTA1;SPTB;EPB41;GYPC	4	Hereditary elliptocytosis (HE) is a rare clinically and genetically heterogeneous disorder of the red cell membrane characterized by manifestations ranging from mild to severe transfusion-dependent hemolytic anemia but with the majority of patients being asymptomatic.	Rare genetic hematologic disease
Orphanet:228179	Autosomal dominant Charcot-Marie-Tooth disease type 2M	DNM2	1	A form of axonal Charcot-Marie-Tooth disease, a peripheral motor and sensory neuropathy, characterized by congenital pstosis and early cataract associated to a mildly progressive peripheral neuropathy of variable onset from birth to the 6th decade, pes cavus, reduced to absent ankles tendon reflexes and sometimes neutropenia.	Rare genetic neurological disorder
Orphanet:231531	Hermansky-Pudlak syndrome type 7	DTNBP1	1	NA	Rare inborn errors of metabolism;Rare genetic eye disease;Rare genetic skin disease;Rare genetic hematologic disease
Orphanet:231537	Hermansky-Pudlak syndrome type 8	BLOC1S3	1	NA	Rare inborn errors of metabolism;Rare genetic eye disease;Rare genetic skin disease;Rare genetic hematologic disease
Orphanet:231512	Hermansky-Pudlak syndrome without pulmonary fibrosis	HPS3;HPS5;HPS6	3	Hermansky-Pudlak syndrome without pulmonary fibrosis as a complication includes three relatively mild types (HPS-3, HPS-5 and HPS-6) of Hermansky-Pudlak syndrome (HPS; see this term), a multi-system disorder characterized by ocular or oculocutaneous albinism, bleeding diathesis and, in some cases, granulomatous colitis.	Rare inborn errors of metabolism;Rare genetic eye disease;Rare genetic skin disease;Rare genetic hematologic disease
Orphanet:256	Early-onset generalized limb-onset dystonia	TOR1A	1	A rare movement disorder characterized by involuntary, repetitive, sustained muscle contractions or postures that typically begins in a single limb and, in most individuals, followed by progressive involvement of other limbs and the trunk, typically sparing the cranial and cervical region.	Rare genetic neurological disorder
Orphanet:231500	Hermansky-Pudlak syndrome with pulmonary fibrosis	HPS1;HPS4	2	Hermansky-Pudlak syndrome with pulmonary fibrosis as a complication includes two types (HPS-1 and HPS-4) of Hermansky-Pudlak syndrome (HPS; see this term), a multi-system disorder characterized by oculocutaneous albinism, bleeding diathesis and, in some cases, pulmonary fibrosis or granulomatous colitis.	Rare inborn errors of metabolism;Rare genetic eye disease;Rare genetic skin disease;Rare genetic hematologic disease
Orphanet:2073	Narcolepsy type 1	HCRT;HLA-DRB1;HLA-DQB1;MOG;TNFSF4;P2RY11;ZNF365;CTSH	8	Narcolepsy with cataplexy is a sleep disorder characterized by excessive day-time sleepiness associated with uncontrollable sleep urges and cataplexy (loss of muscle tone often triggered by pleasant emotions).	
Orphanet:231401	Alpha-thalassemia-myelodysplastic syndrome	ATRX	1	An acquired form of alpha-thalassemia characterized by a myelodysplastic syndrome (MDS) or more rarely a myeloproliferative disease (MPD) associated with hemoglobin H disease (HbH).	Rare genetic hematologic disease
Orphanet:231393	Beta-thalassemia-X-linked thrombocytopenia syndrome	GATA1	1	Beta-thalassemia - X-linked thrombocytopenia is a form of beta-thalassemia (see this term) characterized by splenomegaly and petechiae, moderate thrombocytopenia, prolonged bleeding time due to platelet dysfunction, reticulocytosis and mild beta-thalassemia.	Rare genetic hematologic disease
Orphanet:231249	Hemoglobin E-beta-thalassemia syndrome	HBB	1	Hemoglobin E - beta-thalassemia (HbE - BT) is a form of beta-thalassemia (see this term) that results in a mild to severe clinical presentation ranging from a condition indistinguishable from beta-thalassemia major to a mild form of beta-thalassemia intermedia (see these terms).	Rare genetic hematologic disease
Orphanet:2197	Idiopathic hypercalciuria	ADCY10	1	NA	Rare genetic renal disease
Orphanet:231242	Hemoglobin C-beta-thalassemia syndrome	HBB	1	Hemoglobin C - beta-thalassemia (HbC - BT) is a form of beta-thalassemia (see this term) resulting in moderate hemolytic anemia.	Rare genetic hematologic disease
Orphanet:231237	Delta-beta-thalassemia	HBB;HBG1;HBD	3	Delta-beta-thalassemia is a form of beta-thalassemia (see this term) characterized by decreased or absent synthesis of the delta- and beta-globin chains with a compensatory increase in expression of fetal gamma-chain synthesis.	Rare genetic hematologic disease
Orphanet:231226	Dominant beta-thalassemia	HBB	1	Dominant beta-thalassemia is a form of beta-thalassemia (see this term) resulting in moderate to severe anemia.	Rare genetic hematologic disease;Rare genetic endocrine disease;Rare genetic renal disease
Orphanet:231222	Beta-thalassemia intermedia	HBB	1	Beta-thalassemia (BT) intermedia is a form of BT (see this term) characterized by mild to moderate anemia which does not or only occasionally requires transfusion.	Rare genetic hematologic disease;Rare genetic endocrine disease;Rare genetic renal disease
Orphanet:231214	Beta-thalassemia major	HBB	1	Beta-thalassemia (BT) major is a severe early-onset form of BT (see this term) characterized by severe anemia requiring regular red blood cell transfusions.	Rare genetic hematologic disease;Rare genetic endocrine disease;Rare genetic renal disease
Orphanet:2841	Familial benign chronic pemphigus	ATP2C1	1	Benign chronic familial pemphigus of Hailey-Hailey is characterized by rhagades mostly located in the armpits, inguinal and perineal folds (scrotum, vulva).	Rare genetic skin disease
Orphanet:231183	Usher syndrome type 3	CEP78;CLRN1;MT-TS2;HARS	4	NA	Genetic otorhinolaryngologic disease;Rare genetic eye disease;Ciliopathy
Orphanet:347	Frasier syndrome	WT1	1	Frasier syndrome is characterised by the association of male pseudohermaphrodism and glomerular nephropathy. This syndrome is associated with a high risk of developing gonadoblastoma.	Inherited cancer-predisposing syndrome;Rare genetic renal disease;Rare genetic gynecological and obstetrical diseases;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease
Orphanet:231178	Usher syndrome type 2	USH2A;ADGRV1;MYO7A;WHRN;PDZD7	5	NA	Genetic otorhinolaryngologic disease;Rare genetic eye disease;Ciliopathy
Orphanet:2596	Myopathy and diabetes mellitus	MT-TE	1	A rare, genetic, mitochondrial DNA-related mitochondrial myopathy disorder characterized by slowly progressive muscular weakness (proximal greater than distal), predominantly involving the facial muscles and scapular girdle, associated with insulin-dependent diabetes mellitus. Neurological involvement and congenital myopathy may be variably observed.	Rare genetic neurological disorder;Rare genetic endocrine disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:231154	Combined immunodeficiency due to partial RAG1 deficiency	RAG1	1	Combined immunodeficiency due to partial RAG1 deficiency is a form of combined T and B cell immunodeficiency (CID; see this term) characterized by severe and persistent cytomegalovirus (CMV) infection and autoimmune cytopenia.	Rare genetic immune disease
Orphanet:231160	Familial cerebral saccular aneurysm	ANGPTL6;COL3A1;ENG;TGFBR3	4	A rare genetic neurovascular malformation characterized by sac-like bulging of cerebral arteries due to weakening of the endothelial layer. Familial occurrence is suspected when two or more affected first- to third-degree relatives are present in a family. Aneurysms may remain asymptomatic throughout life, or rupture and thereby cause potentially life-threatening subarachnoid hemorrhage. Patients with familial cerebral saccular aneurysm are more likely to develop more than one brain aneurysm, are at greater risk of rupture, and tend to have poorer outcome after rupture than patients with sporadic cerebral aneurysms.	Rare genetic neurological disorder
Orphanet:2966	Properdin deficiency	CFP	1	Properdin deficiency is a rare, hereditary, primary immunodeficiency due to a complement cascade protein anomaly characterized by significantly increased susceptibility to Neisseria species infections. It only affects males, typically presenting with severe or fulminant meningococcal disease.	Rare genetic immune disease
Orphanet:231169	Usher syndrome type 1	USH1K;CDH23;USH1C;USH1G;MYO7A;PCDH15;USH1E;USH1H;CIB2	9	NA	Genetic otorhinolaryngologic disease;Rare genetic eye disease;Ciliopathy
Orphanet:231140	Silver-Russell syndrome due to an imprinting defect of 11p15	H19;IGF2	2	NA	Inherited cancer-predisposing syndrome;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:231144	Silver-Russell syndrome due to 11p15 microduplication	H19;IGF2	2	NA	Inherited cancer-predisposing syndrome;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare chromosomal anomaly
Orphanet:231120	Beckwith-Wiedemann syndrome due to CDKN1C mutation	CDKN1C	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic renal disease;Inherited cancer-predisposing syndrome;Rare genetic cardiac disease
Orphanet:231127	Beckwith-Wiedemann syndrome due to 11p15 microdeletion	H19	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic renal disease;Inherited cancer-predisposing syndrome;Rare genetic cardiac disease;Rare chromosomal anomaly
Orphanet:231108	Familial rhabdoid tumor	SMARCB1;SMARCA4	2	NA	Rare genetic tumor
Orphanet:231117	Beckwith-Wiedemann syndrome due to imprinting defect of 11p15	H19;KCNQ1OT1;IGF2	3	NA	Rare genetic developmental defect during embryogenesis;Rare genetic renal disease;Inherited cancer-predisposing syndrome;Rare genetic cardiac disease
Orphanet:231040	Familial generalized lentiginosis	SASH1	1	Familial generalized lentiginosis is a rare, inherited, skin hyperpigmentation disorder characterized by widespread lentigines without associated noncutaneous abnormalities. Patients present multiple brown to dark brown, non-elevated macula of 0.2 to 1 cm in diameter, spread over the entire body, sometimes including palms or soles, but never oral mucosa.	Rare genetic skin disease
Orphanet:3318	Essential thrombocythemia	TET2;JAK2;MPL;CALR;SH2B3;TP53	6	 450 x 109/L) with a tendency for thrombosis and hemorrhage.	
Orphanet:230857	Ehlers-Danlos/osteogenesis imperfecta syndrome	COL1A1;COL1A2	2	A rare systemic disease characterized by the association of the features of Ehlers-Danlos syndrome with those of osteogenesis imperfecta. Predominant clinical manifestations include generalized joint hypermobility and dislocations, skin hyperextensibility and/or translucency, easy bruising, and invariable association with mild signs of osteogenesis imperfecta, including short stature, blue sclera, and osteopenia or fractures.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic skin disease
Orphanet:230851	Cardiac-valvular Ehlers-Danlos syndrome	FLNA;COL1A2	2	Ehlers-Danlos syndrome, cardiac valvular type is a form of Ehlers-Danlos syndrome characterized by soft skin, skin hyperextensibility, easy bruisability, atrophic scar formation, joint hypermobility and cardiac valvular defects comprising mitral and/or aortic valve insufficiency.	Rare genetic cardiac disease;Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic systemic or rheumatologic disease
Orphanet:82	Hereditary thrombophilia due to congenital antithrombin deficiency	SERPINC1	1	Hereditary thrombophilia due to congenital antithrombin deficiency is a rare, genetic, hematological disease characterized by decreased levels of antithrombin activity in plasma resulting in impaired inactivation of thrombin and factor Xa. Patients have an increased risk for venous thromboembolism, usually in the deep veins of the arms, legs and pulmonary system and, on occasion, in other venous territories (e.g. cerebral veins or sinus, mesenteric, portal, hepatic, renal and/or retinal veins).	Serpinopathy;Rare genetic hematologic disease;Rare genetic bone disease
Orphanet:230845	Vascular-like classical Ehlers-Danlos syndrome	COL1A1	1	NA	NA
Orphanet:230839	Classical-like Ehlers-Danlos syndrome type 1	TNXB	1	Ehlers-Danlos syndrome due to tenascin-X deficiency is a type of Ehlers-Danlos syndrome characterized by generalized joint hypermobility, skin hyperextensibility and easy bruising without atrophic scarring. Other common features include foot and hand deformities (piezogenic papules, pes planus, broad forefeet, brachydactyly, and acrogenic skin of hands), severe fatigue and neuromuscular symptoms including muscle weakness and myalgia.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic systemic or rheumatologic disease;Rare genetic odontologic disease
Orphanet:238269	AApoAII amyloidosis	APOA2	1	NA	Rare genetic renal disease;Rare genetic systemic or rheumatologic disease
Orphanet:238446	15q11q13 microduplication syndrome	UBE3A	1	The 15q11-q13 microduplication (dup15q11-q13) syndrome is characterized by neurobehavioral disorders, hypotonia, cognitive deficit, language delay and seizures. Prevalence is unknown.	Rare chromosomal anomaly
Orphanet:238329	Severe X-linked mitochondrial encephalomyopathy	AIFM1	1	Severe X-linked mitochondrial encephalomyopathy is an extremely rare mitochondrial respiratory chain disease resulting in a neurodegenerative disorder characterized by psychomotor delay, hypotonia, areflexia, muscle weakness and wasting in the two patients reported to date.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:231568	Generalized dominant dystrophic epidermolysis bullosa	COL7A1	1	Generalized dominant dystrophic epidermolysis bullosa (DDEB-gen) is a subtype of dystrophic epidermolysis bullosa (DEB, see this term), formerly known as DDEB, Pasini and Cockayne-Touraine types, characterized by generalized blistering, milia formation, atrophic scarring, and dystrophic nails.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:231671	Isolated growth hormone deficiency type IB	GH1;GHRHR	2	NA	Rare genetic endocrine disease
Orphanet:1900	Kyphoscoliotic Ehlers-Danlos syndrome due to lysyl hydroxylase 1 deficiency	PLOD1	1	Ehlers-Danlos syndrome, kyphoscoliotic type (EDKT) is a form of Ehlers-Danlos syndrome characterized by severe hypotonia and kyphoscoliosis at birth, generalized joint hyperextensibility and ocular globe fragility.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic systemic or rheumatologic disease
Orphanet:231679	Isolated growth hormone deficiency type II	GH1;POU1F1	2	NA	Rare genetic endocrine disease
Orphanet:286	Vascular Ehlers-Danlos syndrome	COL3A1;COL5A1	2	Ehlers-Danlos syndrome type IV, also known as the vascular type of Ehlers-Danlos syndrome (EDS), is an inherited connective tissue disorder defined by characteristic facial features (acrogeria) in most patients, translucent skin with highly visible subcutaneous vessels on the trunk and lower back, easy bruising, and severe arterial, digestive and uterine complications, which are rarely, if at all, observed in the other forms of EDS.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic systemic or rheumatologic disease;Rare genetic vascular disease
Orphanet:285	Hypermobile Ehlers-Danlos syndrome	TNXB	1	Ehlers-Danlos syndrome, hypermobility type (HT-EDS) is the most frequent form of EDS (see this term), a group of hereditary connective tissue diseases, and is characterized by joint hyperlaxity, mild skin hyperextensibility, tissue fragility and extra-musculoskeletal manifestations.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic systemic or rheumatologic disease
Orphanet:231662	Isolated growth hormone deficiency type IA	GH1;RNPC3	2	NA	Rare genetic endocrine disease
Orphanet:257	Epidermolysis bullosa simplex with muscular dystrophy	PLEC	1	Epidermolysis bullosa simplex with muscular dystrophy (EBS-MD) is a basal subtype of epidermolysis bullosa simplex (EBS, see this term) characterized by generalized blistering associated with muscular dystrophy.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic skin disease
Orphanet:1901	Dermatosparaxis Ehlers-Danlos syndrome	ADAMTS2	1	, has been localised to 5q23. The homozygous mutation Q225X was present in 80% of cases subjected to molecular analysis. There is no specific treatment available for this disease, but symptomatic management should be offered in a specialised centre.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic systemic or rheumatologic disease
Orphanet:231720	Non-acquired combined pituitary hormone deficiency-sensorineural hearing loss-spine abnormalities syndrome	LHX3	1	Non-acquired combined pituitary hormone deficiency-sensorineural hearing loss-spine abnormalities syndrome is a rare, genetic, non-acquired, combined pituitary hormone deficiency disorder characterized by panhypopituitarism (with or without ACTH deficiency) associated with spine abnormalities, including frequent rigid cervical spine and short neck with limited rotation, and variable degrees of sensorineural hearing loss. The anterior pituitary gland is usually abnormal (typically hypoplastic) and rarely a mild developmental delay or intellectual disability may be associated.	Genetic otorhinolaryngologic disease;Rare genetic endocrine disease
Orphanet:839	Congenital nephrotic syndrome, Finnish type	NPHS1	1	 or during the first 3 months of life.	Rare genetic renal disease
Orphanet:531	Miller-Dieker syndrome	HIC1;YWHAE;PAFAH1B1	3	Miller-Dieker Syndrome (MDS) is a contiguous gene deletion syndrome of chromosome 17p13.3, characterised by classical lissencephaly (lissencephaly type 1) and distinct facial features. Additional congenital malformations can be part of the condition.	Rare chromosomal anomaly;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:1083	Microlissencephaly	NDE1;KATNB1	2	Microlissencephaly describes a heterogenous group of a rare cortical malformations characterized by lissencephaly in combination with severe congenital microcephaly, presenting with spasticity, severe developmental delay, and seizures and with survival varying from days to years.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:452	X-linked lissencephaly with abnormal genitalia	ARX	1	X-linked lissencephaly with abnormal genitalia (XLAG) is a rare, genetic, central nervous system malformation disorder characterized, in males, by lissencephaly (with posterior predominance and moderately thickened cortex), complete absence of corpus callosum, neonatal-onset (mainly perinatal) intractable seizures, postnatal microcephaly, severe hypotonia, poor responsiveness and hypogonadism (micropenis, hypospadias, cryptorchidism, small scrotal sac). Defective temperature regulation and chronic diarrhea may be additionally observed.	Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease;Rare genetic neurological disorder
Orphanet:238763	Glaucoma secondary to spherophakia/ectopia lentis and megalocornea	LTBP2	1	Glaucoma secondary to spherophakia/ectopia lentis and megalocornea is a rare, genetic, non-syndromic developmental defect of the eye disorder characterized by congenital megalocornea associated with spherophakia and/or ectopia lentis leading to pupillary block and secondary glaucoma. Additional features may include flat irides, iridodonesis, axial myopia, very deep anterior chambers, miotic, oval pupils without well-defined borders, ocular pain and irritability manifesting as conjunctival injection, corneal edema and central scarring, as well as a high arched palate.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:238722	Familial congenital mirror movements	DNAL4;RAD51;DCC;NTN1	4	A rare, genetic, movement disorder characterized by involuntary movements on one side of the body that mirror intentional movements on the opposite side of the body, which are present in various first-degree members of a family, persist beyond the first decade of life, and have no associated comorbidities.	Rare genetic neurological disorder
Orphanet:238769	1q44 microdeletion syndrome	HNRNPU	1	1q44 microdeletion syndrome is a newly described syndrome associated with facial dysmorphism, developmental delay, in particular of expressive speech, seizures and hypotonia.	Rare chromosomal anomaly
Orphanet:238505	Combined immunodeficiency due to CD27 deficiency	ITK;CD27	2	A rare combined T and B cell immunodeficiency with a predisposition to lymphoproliferative syndrome. It is characterized by persistent symptomatic EBV-viremia and hypogammaglobulinemia variably presenting with fever, lymphadenopathy and systemic inflammatory conditions including hepatitis, pneumonia and sepsis. It may be associated with lymphoma, hemophagocytic lymphohistiocytosis, and aplastic anemia.	Rare genetic immune disease;Inherited cancer-predisposing syndrome
Orphanet:238475	Familial hypercholanemia	EPHX1;TJP2;BAAT	3	Familial hypercholanemia is a very rare genetic disorder characterized clinically by elevated serum bile acid concentrations, itching, and fat malabsorption reported in patients of Old Order Amish descent.	Rare genetic hepatic disease;Rare inborn errors of metabolism
Orphanet:238455	Infantile dystonia-parkinsonism	SLC6A3	1	Infantile dystonia-parkinsonism (IPD) is an extremely rare inherited neurological syndrome that presents in early infancy with hypokinetic parkinsonism and dystonia and that can be fatal.	Rare genetic neurological disorder
Orphanet:238459	SLC35A1-CDG	SLC35A1	1	SLC35A1-CDG is an extremely rare form of CDG syndrome (see this term) characterized clinically in the single reported case by repeated hemorrhagic incidents, including severe pulmonary hemorrhage.	Rare inborn errors of metabolism;Rare genetic neurological disorder;Rare genetic renal disease
Orphanet:238578	Familial clubfoot due to 17q23.1q23.2 microduplication	TBX4	1	17q23.1-q23.2 microduplication is a newly described cause of familial isolated clubfoot.	Rare chromosomal anomaly;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:238557	Chuvash erythrocytosis	VHL	1	Chuvash erythrocytosis is a rare, genetic, congenital secondary polycythemia disorder characterized by increased hemoglobin, hematocrit and erythropoietin serum levels and normal oxygen affinity, which usually manifests with headache, dizziness, dyspnea and/or plethora. Patients present an increased risk of hemorrhage, thrombosis and early death.	Rare genetic hematologic disease
Orphanet:238569	Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections syndrome	IL10;IL10RA;IL10RB	3	A rare immune dysregulation disease with immunodeficiency characterized by severe, progressive infantile onset inflammatory bowel disease with pancolitis, perianal disease (ulceration, fistulae), recurrent respiratory, genitourinary and cutaneous infections, arthritis and a high risk of B-cell lymphoma.	Rare genetic immune disease;Rare genetic gastroenterological disease
Orphanet:238523	Atypical hypotonia-cystinuria syndrome	SLC3A1;PREPL;CAMKMT	3	A form of hypotonia-cystinuria type 1 syndrome characterized by mild to moderate intellectual disability in addition to classic hypotonia-cystinuria syndrome phenotype (cystinuria type 1, generalised hypotonia, poor feeding, growth retardation, and minor facial dysmorphism).	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare chromosomal anomaly;Rare genetic renal disease
Orphanet:238613	Beckwith-Wiedemann syndrome due to NSD1 mutation	NSD1	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic renal disease;Inherited cancer-predisposing syndrome;Rare genetic cardiac disease
Orphanet:238670	Isolated thyrotropin-releasing hormone deficiency	TRH	1	NA	Rare genetic endocrine disease
Orphanet:240885	NA	UGT1A1	1	NA	NA
Orphanet:240887	NA	NAT2	1	NA	NA
Orphanet:240869	NA	CYP2B6	1	NA	NA
Orphanet:240867	NA	CYP2D6	1	NA	NA
Orphanet:240871	NA	HLA-B	1	NA	NA
Orphanet:240921	NA	CYP2C19	1	NA	NA
Orphanet:240905	NA	UGT1A1	1	NA	NA
Orphanet:240071	Classic progressive supranuclear palsy syndrome	MAPT	1	Classical progressive supranuclear palsy, also known as Richardson's syndrome, is the most common clinical variant of progressive supranuclear palsy (PSP; see this term), a rare late-onset neurodegenerative disease characterized by postural instability, progressive rigidity, supranuclear gaze palsy and mild dementia.	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:240112	Progressive supranuclear palsy-progressive non-fluent aphasia syndrome	MAPT	1	PSP-progressive non fluent aphasia (PSP-PNFA) is an atypical variant of progressive supranuclear palsy (PSP; see this term), a rare late-onset neurodegenerative disease. Unlike classic PSP (Richardson syndrome) patients present with an isolated speech production problem years before developing other motor features of PSP.	NA
Orphanet:240103	Progressive supranuclear palsy-corticobasal syndrome	MAPT	1	PSP-corticobasal syndrome (PSP-CBS) is an atypical variant of progressive supranuclear palsy (PSP; see this term), a rare late-onset neurodegenerative disease.	NA
Orphanet:240094	Progressive supranuclear palsy-pure akinesia with gait freezing syndrome	MAPT	1	PSP-Pure akinesia with gait freezing (PSP-PAGF) is an atypical variant of progressive supranuclear palsy (PSP; see this term), a rare late-onset neurodegenerative disease.	NA
Orphanet:240085	Progressive supranuclear palsy-parkinsonism syndrome	MAPT	1	PSP-parkinsonism (PSP-P) is an atypical variant of progressive supranuclear palsy (PSP; see this term), a rare late-onset neurodegenerative disease.	
Orphanet:240863	NA	TPMT;COMT	2	NA	NA
Orphanet:240839	NA	TYMS;DPYD	2	NA	NA
Orphanet:240841	NA	HLA-B	1	NA	NA
Orphanet:240760	Nijmegen breakage syndrome-like disorder	MRE11;RAD50	2	Nijmegen breakage syndrome-like disorder is a rare, genetic multiple congenital anomalies/dysmorphic syndrome characterized by growth retardation, short stature, developmental delay, intellectual disability, craniofacial dysmorphism (i.e. severe microcephaly, sloping forehead, prominent eyes, broad nasal ridge, hypoplastic nasal septum, epicanthal folds), spontaneous chromosomal instability, cellular hypersensitivity to ionizing radiation and radioresistant DNA synthesis, without severe infections, immunodeficiency or cancer predisposition. Additional reported features include mild spasticity, slight and nonprogressive ataxia, hyperopia, multiple pigmented nevi, widely spaced nipples, and clinodactyly.	Rare genetic developmental defect during embryogenesis;Inherited cancer-predisposing syndrome;Rare genetic immune disease
Orphanet:240845	NA	HLA-B	1	NA	NA
Orphanet:241043	NA	CYP3A5;CYP3A4	2	NA	NA
Orphanet:240947	NA	CYP2D6	1	NA	NA
Orphanet:240935	NA	P2RY12;CYP2C19	2	NA	NA
Orphanet:331226	Susceptibility to infection due to TYK2 deficiency	TYK2	1	Susceptibility to infection due to TYK2 deficiency is a rare primary immunodeficiency characterized by increased susceptibility to intracellular bacterial and viral infection, with or without increased serum IgE. Clinical manifestations are highly variable, depending on the infection type and location, and can include recurrent otitis, sinusitis, pulmonary and cutaneous infections, meningitis and internal abscesses.	Rare genetic immune disease
Orphanet:331176	Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency	G6PC3	1	 gene. Cardiac malformations (e.g. atrial septal defects, patent ductus arteriosus,valvular defects), urogenital anomalies (incl. cryptorchidism), growth and developmental delay, facial dysmorphism (e.g. frontal bossing, upturned nose, malar hypoplasia), and intermittent thrombocytopenia are frequently associated.	Rare genetic immune disease
Orphanet:331187	Immunodeficiency due to MASP-2 deficiency	MASP2	1	Immunodeficiency due to MASP-2 deficiency is a rare, genetic immunodeficiency due to a complement cascade protein anomaly characterized by low serum levels of MASP-2 and a variable susceptibility to bacterial infections (e.g. pulmonary tuberculosis, pneumococcal pneumonia, skin abscesses and sepsis), and autoimmune diseases (e.g. inflammatory lung disease, cystic fibrosis, systemic lupus erythematosus). In many cases it remains asymptomatic.	Rare genetic immune disease
Orphanet:331190	Immunodeficiency due to ficolin3 deficiency	FCN3	1	 to childhood-onset recurrent pulmonary infections leading to brain abscesses and pulmonary fibrosis, to membranous nephropathy. In some patients, clinical consequences of ficolin3 deficiency were not clear.	Rare genetic immune disease
Orphanet:331206	Severe combined immunodeficiency due to complete RAG1/2 deficiency	RAG1;RAG2	2	Severe combined immunodeficiency due to complete RAG1/2 deficiency is a rare, genetic T-B- severe combined immunodeficiency disorder due to null mutations in recombination activating gene (RAG) 1 and/or RAG2 resulting in less than 1% of wild type V(D)J recombination activity. Patients present with neonatal onset of life-threatening, severe, recurrent infections by opportunistic fungal, viral and bacterial micro-organisms, as well as skin rashes, chronic diarrhea, failure to thrive and fever. Immunologic observations include profound T- and B-cell lymphopenia, normal NK counts and low or absent serum immunoglobulins; some patients may have eosinophilia.	Rare genetic immune disease
Orphanet:330032	Hemoglobin Lepore-beta-thalassemia syndrome	HBB;HBD	2	NA	Rare genetic hematologic disease
Orphanet:330041	Hemoglobin M disease	HBA2;HBB;HBA1	3	NA	Rare genetic hematologic disease
Orphanet:330050	DNM1L-related encephalopathy due to mitochondrial and peroxisomal fission defect	DNM1L	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:330054	Congenital cataract-progressive muscular hypotonia-hearing loss-developmental delay syndrome	GFER	1	Congenital cataract-progressive muscular hypotonia-hearing loss-developmental delay syndrome is a rare, genetic, mitochondrial myopathy disorder characterized by congenital cataract, progressive muscular hypotonia that particularly affects the lower limbs, reduced deep tendon reflexes, sensorineural hearing loss, global development delay and lactic acidosis. Muscle biopsy reveals reduced complex I, II and IV respiratory chain activity.	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:329802	5p13 microduplication syndrome	NIPBL	1	A rare partial autosomal trisomy/tetrasomy characterized by global developmental delay, intellectual disability, autistic behavior, muscular hypotonia, macrocephaly and facial dysmorphism (frontal bossing, short palpebral fissures, low set, dysplastic ears, short or shallow philtrum, high arched or narrow palate, micrognathia). Other associated clinical features include sleep disturbances, seizures, aplasia/hypoplasia of the corpus callosum, skeletal abnormalities (large hands and feet, long fingers and toes, talipes).	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare chromosomal anomaly
Orphanet:329475	Spastic paraplegia-Paget disease of bone syndrome	VCP	1	Spastic paraplegia-Paget disease of bone syndrome is an extremely rare, complex form of hereditary spastic paraplegia characterized by a slowly progressive spastic paraplegia (with increased muscle tone, decreased strength in the anterior tibial muscles and hyperreflexia in the lower extremities with Babinski sign) presenting in adulthood, associated with Paget disease of the bone. Cognitive decline, dementia and myopathic changes at muscle biopsy have not been reported.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic neurological disorder
Orphanet:329481	Lipoprotein glomerulopathy	APOE	1	NA	Rare genetic renal disease;Rare inborn errors of metabolism;Rare genetic endocrine disease
Orphanet:329478	Adult-onset distal myopathy due to VCP mutation	VCP	1	A rare, genetic distal myopathy disorder characterized by middle age-onset of distal leg muscle weakness, atrophy in the anterior compartment resulting in foot drop, without proximal or scapular skeletal muscle weakness. Rapidly progressive dementia, Paget disease of bone and hand weakness have been reported. Muscle biopsy shows pronounced myopathic changes with rimmed vacuoles.	Rare genetic neurological disorder
Orphanet:329931	C3 glomerulonephritis	CFHR1;CFHR5	2	NA	
Orphanet:329971	Generalized juvenile polyposis/juvenile polyposis coli	BMPR1A;SMAD4;ENG	3	NA	Rare genetic gastroenterological disease;Inherited cancer-predisposing syndrome
Orphanet:329967	Intermittent hydrarthrosis	MEFV;TNFRSF1A	2	NA	
Orphanet:329903	Immunoglobulin-mediated membranoproliferative glomerulonephritis	CFH;DGKE	2	NA	Rare genetic renal disease
Orphanet:329308	Fatty acid hydroxylase-associated neurodegeneration	FA2H	1	Fatty acid hydroxylase-associated neurodegeneration (FAHN) is a very rare, autosomal recessive form of neurodegeneration with brain iron accumulation (NBIA) characterized by childhood-onset focal dystonia, progressive spastic paraplegia that progresses to tetra paresis, ataxia, dysarthria, intellectual decline, and oculomotor disturbances (optic atrophy), accompanied by iron deposition in the globus pallidus.	Rare genetic neurological disorder;Rare genetic eye disease;Rare inborn errors of metabolism
Orphanet:329314	Adult-onset multiple mitochondrial DNA deletion syndrome due to DGUOK deficiency	DGUOK	1	An extremely rare multiple mitochondrial DNA deletion syndrome with markedly decreased deoxyguanosine kinase (DGUOK) activity in skeletal muscle characterized by a highly variable phenotype. Clinical manifestations include progressive external ophthalmoplegia, mitochondrial myopathy, recurrent rhabdomyolysis, lower motor neuron disease, mild cognitive impairment, sensory axonal neuropathy, optic atrophy, ataxia, hypogonadism and/or parkinsonism.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:329319	Thrombocythemia with distal limb defects	THPO	1	Thrombocythemia with distal limb defects is a rare, genetic syndrome with limb reduction defects characterized by thrombocytosis, unilateral transverse limb defects (ranging from absence of phalanges to absence of hand or forearm) and splenomegaly.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic hematologic disease
Orphanet:329284	Beta-propeller protein-associated neurodegeneration	WDR45	1	Beta-propeller protein-associated neurodegeneration (BPAN), also known as static encephalopathy of childhood with neurodegeneration in adulthood, is a rare form of neurodegeneration with brain iron accumulation (NBIA) characterized by early-onset developmental delay and further neurological deterioration in early adulthood.	Rare genetic neurological disorder
Orphanet:329457	Distal arthrogryposis type 5D	ECEL1	1	Distal arthrogryposis type 5D is a rare subtype of distal arthrogryposis syndrome characterized by arthrogryposis multiplex congenita affecting the hands, feet, ankle, shoulders and/or neck, with camptodactyly of the fingers and limited knee and hip extension, associated with asymmetric ptosis and, less frequently, other ocular manifestations (e.g. ophthalmoplegia, strabismus). Affected individuals frequently have a bulbous nose, furrowed tongue, micro/retrognathia, a short neck, congenital hip dislocation, club feet, scoliosis and short stature.	Rare genetic developmental defect during embryogenesis
Orphanet:329466	Autosomal dominant focal dystonia, DYT25 type	GNAL	1	A form of focal dystonia characterized by cervical, laryngeal and hand-forearm dystonia.	Rare genetic neurological disorder
Orphanet:329469	Acute megakaryoblastic leukemia without Down syndrome	GLIS2;CBFA2T3	2	NA	
Orphanet:329336	Adult-onset chronic progressive external ophthalmoplegia with mitochondrial myopathy	RRM2B;RNASEH1	2	A rare mitochondrial disease characterized by adult onset of progressive external ophthalmoplegia, exercise intolerance, muscle weakness, manifestations of spinocerebellar ataxia (e.g. impaired gait, dysarthria) and mild motor peripheral neuropathy. Respiratory insufficiency has been reported in some cases.	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:329228	Microcephalic primordial dwarfism due to ZNF335 deficiency	ZNF335	1	Microcephalic primordial dwarfism due to ZNF335 deficiency is characterized by severe antenatal microencephaly, simplified gyration, agenesis of the corpus callosum, absence of basal ganglia (very rare), pontocerebellar atrophy and involvement of the white matter with secondary cerebral atrophy. Congenital cataract, choanal atresia, multiple arthrogryposis and spastic tetraparesis can occur.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:329224	Intellectual disability-craniofacial dysmorphism-cryptorchidism syndrome	PACS1	1	Intellectual disability-craniofacial dysmorphism-cryptorchidism syndrome is a rare, genetic, syndromic intellectual disability syndrome characterized by mild to moderate intellectual disability, developmental delay (with speech and language development more severely affected) and facial dysmorphism which typically includes full, arched eyebrows, hypertelorism, down-slanting palpebral fissures, long eyelashes, ptosis, low-set, simple ears, bulbous nasal tip, flat philtrum, wide mouth with downturned corners and thin upper lip and diastema of the teeth. Association with infantile hypotonia, seizures, cryptorchidism in males and congenital abnormalities, including cardiac, cerebral or occular defects, may be observed.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:329217	Cerebral sinovenous thrombosis	F2;F5;PROZ	3	A rare, potentially life-threatening, circulatory system disease characterized by variable signs and symptoms which may include headache, seizures, altered mental status, intracranial hypertension and cavernous sinus syndrome, among others.	
Orphanet:329211	Autosomal dominant neovascular inflammatory vitreoretinopathy	CAPN5	1	A rare, genetic, vitreoretinal degeneration characterized by a slowly progressive vitreoretinopathy with onset during the second or third decade of life. The disease initially presents as autoimmune uveitis with reduction in the b-wave on electroretinography, and progresses with development of photoreceptor degeneration, vitreous hemorrhage, cystoid macular edema, retinal neovascularization, intraocular fibrosis, secondary glaucoma, and retinal detachment leading to phthisis and complete blindness.	Rare genetic eye disease
Orphanet:329195	Developmental delay with autism spectrum disorder and gait instability	HERC2	1	Developmental delay with autism spectrum disorder and gait instability is a rare, genetic, neurological disorder characterized by infant hypotonia and feeding difficulties, global development delay, mild to moderated intellectual disability, delayed independent ambulation, broad-based gait with arms upheld and flexed at the elbow with brisk walking or running, and limited language skills. Behavior patterns are highly variable and range from sociable and affectionate to autistic behavior.	Rare genetic neurological disorder
Orphanet:329191	Tall stature-scoliosis-macrodactyly of the great toes syndrome	NPR2	1	Tall stature-scoliosis-macrodactyly of the great toes syndrome is a rare, genetic, overgrowth or tall stature syndrome with skeletal involvement characterized by early and proportional overgrowth, osteopenia, lumbar scoliosis, arachnodactyly of the hands and feet, macrodactyly of the hallux, coxa valga with epiphyseal dysplasia of the femoral capital epiphyses and susceptibility to slipped capital femoral epiphysis.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:329178	Congenital muscular dystrophy with intellectual disability and severe epilepsy	DPM2	1	Congenital muscular dystrophy with intellectual disability and severe epilepsy is a rare, fatal, inborn error of metabolism disorder characterized by respiratory distress and severe hypotonia at birth, severe global developmental delay, early-onset intractable seizures, myopathic fascies with craniofacial dysmorphism (trigonocephaly/progressive microcephaly, low anterior hairline, arched eyebrows, hypotelorism, strabismus, small nose, prominent philtrum, thin upper lip, high-arched palate, micrognathia, malocclusion), severe, congenital flexion joint contractures and elevated serum creatine kinase levels. Scoliosis, optic atrophy, mild hepatomegaly, and hypoplastic genitalia may also be associated.	Rare inborn errors of metabolism;Rare genetic hepatic disease;Rare genetic neurological disorder
Orphanet:329258	Autosomal dominant Charcot-Marie-Tooth disease type 2Q	DHTKD1	1	A rare subtype of autosomal dominant Charcot-Marie-Tooth disease type 2, characterized by adolescent to adulthood-onset of symmetrical, slowly progressive distal muscle weakness and atrophy (with a predominant weakness of the distal lower limbs) associated with reduced or absent deep tendon reflexes, pes cavus and mild to moderated deep sensory impairment.	Rare genetic neurological disorder
Orphanet:329249	Severe early-onset obesity-insulin resistance syndrome due to SH2B1 deficiency	SH2B1	1	A rare, genetic form of obesity characterized by severe early-onset obesity, hyperphagia, insulin resistance with hyperinsulinemia, reduced adult final height, delayed speech and language development and a tendency for social isolation and aggressive behavior.	Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease
Orphanet:329242	Congenital chronic diarrhea with protein-losing enteropathy	PLVAP;DGAT1	2	Congenital chronic diarrhea with protein-losing enteropathy is a rare, genetic, intestinal disease characterized by early-onset, chronic, non-infectious, non-bloody, watery diarrhea associated with protein-losing enteropathy which results in hypoalbuminemia, hypogammaglobulinemia and elevated stool alpha-1-antitrypsin. Patients typically present severe, intractable diarrhea, failure to thrive, recurrent infections and edema.	Rare genetic gastroenterological disease
Orphanet:329235	X-linked central congenital hypothyroidism with late-onset testicular enlargement	IGSF1	1	X-linked central congenital hypothyroidism with late-onset testicular enlargement is a rare, genetic, endocrine disease characterized by central hypothyroidism, testis enlargement in adolescence resulting in adult macroorchidism, delayed pubertal testosterone rise with a subsequent delayed pubertal growth spurt, small thyroid gland, and variable prolactin and growth hormone deficiency.	Rare genetic endocrine disease
Orphanet:329173	Autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis	RBCK1;RNF31	2	A rare, genetic, mixed autoinflammatory and autoimmune syndrome characterized by chronic systemic autoinflammation (presenting as recurrent fever in the neonatal or infantile period) and combined immunodeficiency (manifesting as recurrent viral and invasive bacterial infections). Muscular amylopectinosis may be subclinical or be complicated by myopathy/cardiomyopathy.	Rare genetic immune disease;Rare genetic systemic or rheumatologic disease
Orphanet:329	Congenital factor XI deficiency	F11	1	Congenital factor XI deficiency is an inherited bleeding disorder characterized by reduced levels and activity of factor XI (FXI) resulting in moderate bleeding symptoms, usually occurring after trauma or surgery.	Rare genetic hematologic disease
Orphanet:1243	Best vitelliform macular dystrophy	BEST1	1	Best vitelliform macular dystrophy (BVMD) is a genetic macular dystrophy characterized by loss of central visual acuity, metamorphopsia and a decrease in the Arden ratio secondary to an egg yolk-like lesion located in the foveal or parafoveal region.	Rare genetic eye disease
Orphanet:325524	Classic congenital lipoid adrenal hyperplasia due to STAR deficency	STAR	1	NA	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Genetic infertility
Orphanet:325448	Leydig cell hypoplasia due to LHB deficiency	LHB	1	NA	Genetic infertility;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease
Orphanet:325529	Non-classic congenital lipoid adrenal hyperplasia due to STAR deficency	STAR	1	NA	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease
Orphanet:324999	JMP syndrome	PSMB8	1	Joint contractures, muscle atrophy, microcytic anemia and panniculitis-induced lipodystrophy (JMP) syndrome is a rare autoinflammatory disorder belonging to the proteasome disability syndrome (see this term) group and characterized by sclerodermic skin with the presence of erythematous lesions, joint contractures, generalized or partial lipodystrophy, muscle atrophy and short stature.	Rare genetic skin disease;Rare genetic endocrine disease;Rare genetic systemic or rheumatologic disease
Orphanet:325004	CANDLE syndrome	PSMB8	1	Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome is a rare autoinflammatory disorder belonging to the proteasome disability syndrome (see this term) group and is characterized by early-onset recurrent fever, swollen violaceous eyelids, progressive lipodystrophy, arthralgia, purpuric skin lesions and delayed physical development.	Rare genetic skin disease;Rare genetic endocrine disease;Rare genetic immune disease;Rare genetic systemic or rheumatologic disease
Orphanet:324718	ABetaA21G amyloidosis	APP	1	Hereditary cerebral hemorrhage with amyloidosis (HCHWA), Flemish type is a form of HCHWA (see this term) characterized by an age of onset of 45 years of age, progressive Alzheimer's disease-like dementia and lobar intracerebral hemorrhage in some patients.	Rare genetic neurological disorder;Rare genetic systemic or rheumatologic disease
Orphanet:324713	ABeta amyloidosis, Italian type	APP	1	Hereditary cerebral hemorrhage with amyloidosis (HCHWA), Italian type is a form of HCHWA (see this term) characterized by an age of onset of 50 years of age, dementia and lobar intracerebral hemorrhage.	Rare genetic neurological disorder;Rare genetic systemic or rheumatologic disease
Orphanet:324737	SRD5A3-CDG	SRD5A3	1	SRD5A3-CDG is a rare, non X-linked congenital disorder of glycosylation due to steroid 5 alpha reductase type 3 deficiency characterized by a highly variable phenotype typically presenting with severe visual impairment, variable ocular anomalies (such as optic nerve hypoplasia/atrophy, iris and optic nerve coloboma, congenital cataract, glaucoma), intellectual disability, cerebellar abnormalities, nystagmus, hypotonia, ataxia, and/or ichthyosiform skin lesions. Other reported manifestations include retinitis pigmentosa, kyphosis, congenital heart defects, hypertrichosis and abnormal coagulation.	Rare inborn errors of metabolism;Rare genetic skin disease;Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:324723	ABeta amyloidosis, Arctic type	APP	1	Hereditary cerebral hemorrhage with amyloidosis (HCHWA), Arctic type is a form of HCHWA (see this term) characterized by an age of onset of 54-61 years and progressive Alzheimer's disease-like dementia, without intracerebral hemorrhages.	Rare genetic neurological disorder;Rare genetic systemic or rheumatologic disease
Orphanet:324708	ABeta amyloidosis, Iowa type	APP	1	Hereditary cerebral hemorrhage with amyloidosis (HCHWA), Iowa type is a form of HCHWA (see this term) characterized by age of onset between 50-66 years of age, memory impairment, myoclonic jerks, expressive dysphagia, short-stepped gait, personality changes and lobar intracerebral hemorrhages.	Rare genetic neurological disorder;Rare genetic systemic or rheumatologic disease
Orphanet:324703	ABetaL34V amyloidosis	APP	1	Hereditary cerebral hemorrhage with amyloidosis (HCHWA), Piedmont type is a form of HCHWA (see this term) characterized by an age of onset between 50-70 years of age, recurrent lobar intracerebral hemorrhages and cognitive decline.	Rare genetic neurological disorder;Rare genetic systemic or rheumatologic disease
Orphanet:324611	Autosomal dominant Charcot-Marie-Tooth disease type 2 due to KIF5A mutation	KIF5A	1	A rare form of axonal peripheral sensorimotor neuropathy characterized by classical CMT2 signs and symptoms (progressive weakness and atrophy of distal limb muscles, mild sensory deficits of position, vibration and pain/temperature, pes cavus, and symmetrically absent or reduced muscle and sensory action potentials with relatively preserved nerve conduction velocities in neurophysiological studies) as well as pyramidal tract involvement (spasticity, hyperreflexia). Spasticity and pain may be the presenting symptoms.	Rare genetic neurological disorder
Orphanet:324604	Classic multiminicore myopathy	SELENON;TTN;MYH7	3	NA	Rare genetic neurological disorder
Orphanet:324588	Familial dyskinesia and facial myokymia	ADCY5	1	Familial dyskinesia and facial myokymia is a rare paroxysmal movement disorder, with childhood or adolescent onset, characterized by paroxysmal choreiform, dystonic, and myoclonic movements involving the limbs (mostly distal upper limbs), neck and/or face, which can progressively increase in both frequency and severity until they become nearly constant. Patients may also present with delayed motor milestones, perioral and periorbital dyskinesias, dysarthria, hypotonia, and weakness.	Rare genetic neurological disorder
Orphanet:324601	X-linked cleft palate and ankyloglossia	TBX22	1	X-linked cleft palate and ankyloglossia is a rare, genetic developmental defect during embryogenesis syndrome characterized by the association of complete, partial or submucous cleft palate and ankyloglossia. Patients may also present abnormal uvula (e.g. absent, bifid, shortened or laterally deviated), short lingual frenulum and dental anomalies (e.g. buccal crossbite, absent and/or misshapen teeth). Digital abnormalities, such as mild clinodactyly and/or syndactyly, have also been reported.	Rare genetic developmental defect during embryogenesis
Orphanet:324581	Benign Samaritan congenital myopathy	RYR1	1	Benign Samaritan congenital myopathy is a rare, genetic, skeletal muscle disease characterized by severe neonatal hypotonia with respiratory insufficiency, delay in motor milestones, and dysmorphic features including bitemporal narrowing, epicanthal folds and hypertelorism. Affected individuals show gradual improvement in hypotonia and muscle weakness within the first two years of life resulting in minimal clinical manifestations in adulthood.	Rare genetic neurological disorder
Orphanet:324585	Autosomal dominant intermediate Charcot-Marie-Tooth disease with neuropathic pain	MPZ	1	A rare subtype of autosomal dominant intermediate Charcot-Marie-Tooth disease characterized by debilitating neuropathic pain associated with mild, distal, symmetrical lower limb sensory loss and mild or absent motor dysfunction. Patients typically manifest with burning, aching, shooting, or throbbing pain and intermittent paraesthesia in toes, heels and ankles.	Rare genetic neurological disorder
Orphanet:324569	Pontocerebellar hypoplasia type 8	CHMP1A	1	 gene. MRI demonstrates a pontocerebellar hypoplasia with vermis and hemispheres equally affected and mild to severely reduced cerebral white matter volume with a fully formed very thin corpus callosum.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:324575	Hyperinsulinism due to HNF1A deficiency	HNF1A	1	Hyperinsulinism due to HNF1A deficiency is a form of diazoxide-sensitive diffuse hyperinsulinism (DHI), characterized by transient or persistent hyperinsulinemic hypoglycemia (HH) in infancy that is responsive to diazoxide, evolving in to maturity-onset diabetes of the young subtype 1 (MODY-1; see this term) later in life.	Rare genetic endocrine disease;Rare genetic developmental defect during embryogenesis
Orphanet:324561	Hypopigmentation-punctate palmoplantar keratoderma syndrome	ENPP1	1	A rare, genetic, epidermal disease characterized by punctate keratoderma on palms and soles associated with irregularly shaped hypopigmented macules (typically localized on the extremities). Ectopic calcification (e.g. early-onset calcific tendinopathy, calcinosis cutis) and pachyonychia may be occasionally associated.	Rare genetic skin disease
Orphanet:324530	Autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation	PLCG2	1	A rare, mixed autoinflammatory and autoimmune syndrome disorder characterized by recurrent neutrophilic blistering skin lesions, arthralgia, ocular inflammation, inflammatory bowel disease, absence of autoantibodies, and mild immunodeficiency manifested by recurrent sinopulmonary infections and deficiency of circulating antibodies. Inflammatory phenotype is not provoked by cold temperatures.	Rare genetic systemic or rheumatologic disease
Orphanet:324535	Combined oxidative phosphorylation defect type 11	RMND1	1	A rare, genetic, mitochondrial oxidative phosphorylation disorder characterized by a highly variable phenotype which ranges from a fatal neonatal/infantile encephalomyopathy with lactic acidosis, hyporeflexia/areflexia, severe hypotonia and respiratory failure to less severe cases presenting with central hypotonia, global developmental delay, congenital sensorineural hearing loss, and renal disease. Additional, variably observed, clinical features include intellectual disability, seizures, and cardiomyopathy.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:324525	Hypertrophic cardiomyopathy and renal tubular disease due to mitochondrial DNA mutation	MT-TL1	1	A mitochondrial oxidative phosphorylation disorder characterized by hypertrophic and dilated cardiomyopathy, failure to thrive, myopathy with generalized hypotonia and increased creatine kinase, developmental delay and/or regression with cerebral atrophy on brain MRI, renal manifestations including chronic renal failure, renal tubular acidosis and lactic acidosis. Additional clinical features include seizures and respiratory failure.	Rare genetic cardiac disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic renal disease
Orphanet:324442	Autosomal recessive axonal neuropathy with neuromyotonia	HINT1	1	A rare peripheral neuropathy characterized by slowly progressive axonal, motor greater than sensory, polyneuropathy combined with neuromytonia (including spontaneous muscular activity at rest (myokymia), impaired muscle relaxation (pseudomyotonia), and contractures of hands and feet) and neuromyotonic or myokymic discharges on needle EMG. It presents with distal lower limb weakness with gait impairment, muscle stiffness, fasciculations and cramps in hands and legs worsened by cold, decreased to absent tendon reflexes, intrinsic hand muscle atrophy and, variably, mild distal sensory impairment.	Rare genetic neurological disorder
Orphanet:324422	ALG13-CDG	ALG13	1	 (Xq23).	Rare genetic hepatic disease;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:324410	X-linked intellectual disability-cardiomegaly-congestive heart failure syndrome	CLIC2	1	X-linked intellectual disability-cardiomegaly-congestive heart failure syndrome is a rare X-linked syndromic intellectual disability disorder characterized by profound intellectual disability, global developmental delay with absent speech, seizures, large joint contractures, abnormal position of thumbs and middle-age onset of cardiomegaly and atrioventricular valve abnormalities, resulting in subsequent congestive heart failure. Additional features include variable facial dysmorphism (notably large ears with overfolded helix) and large testes.	Rare genetic neurological disorder;Rare genetic cardiac disease
Orphanet:324321	Sinoatrial node dysfunction and deafness	CACNA1D	1	Sinoatrial node dysfunction and deafness is a rare genetic disease characterized by congenital severe to profound deafness with no evidence of vestibular dysfunction, associated with sinoatrial node dysfunction with pronounced bradycardia and increased variability of heart rate at rest and episodic syncopes that may be triggered by enhanced physical activity and stress.	Genetic otorhinolaryngologic disease;Rare genetic cardiac disease
Orphanet:324299	Multiple paragangliomas associated with polycythemia	EPAS1	1	A rare, endocrine disease characterized by early onset of polycythemia, and later occuring multiple parangliomas. Clinical presentation includes hypertension, headaches, fatigue, nausea, anxiety, and high concentration of red blood cells, leading to increased risk of stroke and pulmonary thrombembolism.	
Orphanet:324294	T-cell immunodeficiency with epidermodysplasia verruciformis	RHOH	1	A rare primary immunodeficiency characterized by increased susceptibility to infection by human papillomavirus, presenting in childhood with disseminated flat wart-like cutaneous lesions. Burkitt lymphoma has also been reported. Whilst total T-cell counts are normal, there is impaired TCR signaling, profound peripheral naive T-cell lymphopenia with memory T-cells displaying an exhaustion phenotype.	Rare genetic immune disease
Orphanet:324290	Early-onset Lafora body disease	PRDM8	1	Early-onset Lafora body disease is an extremely rare, inherited form of progressive myoclonic epilepsy characterized by progressive myoclonus epilepsy and Lafora bodies, with an early onset (at around 5 years) and a prolonged disease course. Other manifestations include progressive dysarthria, ataxia, cognitive decline, psychosis, dementia, spasticity, dysarthria, myoclonus, and ataxia. The disease course typically extends for several decades.	Rare genetic neurological disorder
Orphanet:324262	Autosomal recessive congenital cerebellar ataxia due to MGLUR1 deficiency	GRM1	1	A rare, genetic, slowly progressive neurodegenerative disease resulting from MGLUR1 deficiency characterized by global developmental delay (beginning in infancy), mild to severe intellectual deficit with poor or absent speech, moderate to severe stance and gait ataxia, pyramidal signs (e.g. hyperreflexia) and mild dysdiadochokinesia, dysmetria, tremors, and/or dysarthria. Oculomotor signs, such as nystagmus, strabismus, ptosis and hypometric saccades, may also be associated. Brain imaging reveals progressive, generalized, moderate to severe cerebellar atrophy, inferior vermian hypoplasia, and/or constitutionally small brain.	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:320360	MT-ATP6-related mitochondrial spastic paraplegia	MT-ATP6	1	MT-ATP6-related mitochondrial spastic paraplegia is a rare, genetic, complex hereditary spastic paraplegia disorder characterized by adulthood-onset of slowly progressive, bilateral, mainly lower limb spasticity and distal weakness associated with lower limb pain, hyperreflexia, and reduced vibration sense. Axonal neuropathy is frequently observed on electromyography and nerve conduction examination.	Rare genetic neurological disorder
Orphanet:320355	Autosomal dominant spastic paraplegia type 41	SPG41	1	A pure form of hereditary spastic paraplegia characterized by onset in adolescence or early adulthood of slowly progressive spastic paraplegia, proximal muscle weakness of the lower extremities and small hand muscles, hyperreflexia, spastic gait and mild urinary compromise.	Rare genetic neurological disorder
Orphanet:320370	Autosomal recessive spastic paraplegia type 43	C19ORF12	1	Autosomal recessive spastic paraplegia type 43 is a rare, complex hereditary spastic paraplegia characterized by a childhood to adolescent onset of progressive lower limb spasticity, associated with mild to severe gait disturbances, extensor plantar responses, muscle weakness and severe distal atrophy, frequently with upper limb involvement. Additional features may include joint contractures, distal sensory loss and brisk or absent deep tendon reflexes. Other signs, such as depression, memory loss, optic atrophy (with vision loss) and brain iron deposition (revealed by brain imagery), have also been reported.	Rare genetic neurological disorder
Orphanet:320365	Autosomal dominant spastic paraplegia type 36	SPG36	1	A complex form of hereditary spastic paraplegia, characterized by an onset in childhood or adulthood of progressive spastic paraplegia (with spastic gait, spasticity, lower limb weakness, pes cavus and urinary urgency) associated with the additional manifestation of peripheral sensorimotor neuropathy.	Rare genetic neurological disorder
Orphanet:320380	Autosomal recessive spastic paraplegia type 54	DDHD2	1	 gene (8p11.23) encoding phospholipase DDHD2.	Rare genetic neurological disorder
Orphanet:320375	Autosomal recessive spastic paraplegia type 55	C12ORF65	1	 gene (12q24.31) encoding probable peptide chain release factor C12orf65, mitochondrial.	Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:320391	Autosomal recessive spastic paraplegia type 46	GBA2	1	 gene (9p13.2) encoding non-lysosomal glucosylceramidase.	Rare genetic neurological disorder
Orphanet:320385	Hereditary sensory and autonomic neuropathy due to TECPR2 mutation	TECPR2	1	Hereditary sensory and autonomic neuropathy due to TECPR2 mutation is a rare genetic peripheral neuropathy characterized by early hypotonia evolving to spastic paraparesis, areflexia, decreased pain and temperature sensitivity, autonomic neuropathy, gastroesophageal reflux disease, recurrent pneumonia and respiratory problems. Patients also have intellectual disability and dysmorphic features, including mild brachycephalic microcephaly, short broad neck, low anterior hairline and coarse face.	Rare genetic neurological disorder
Orphanet:320401	Autosomal recessive spastic paraplegia type 44	GJC2	1	 gene (1q41-q42) encoding the gap junction gamma-2 protein.	Rare genetic neurological disorder
Orphanet:320396	Autosomal recessive spastic paraplegia type 45	NT5C2	1	Autosomal recessive spastic paraplegia type 45 is a rare, pure or complex form of hereditary spastic paraplegia characterized by onset in infancy of progressive lower limb spasticity, abnormal gait, increased deep tendon reflexes and extensor plantar responses, that may be associated with intellectual disability. Additional signs, such as contractures in the lower limbs, amyotrophy, clubfoot and optic atrophy, have also been reported.	Rare genetic neurological disorder
Orphanet:320411	Autosomal recessive spastic paraplegia type 56	CYP2U1	1	A rare form of hereditary spastic paraplegia characterized by delayed walking, toe walking, unsteady and spastic gait, hyperreflexia of the lower limbs, and extensor plantar responses. Upper limbs spasticity and dystonia, subclinical axonal neuropathy, cognitive impairment and intellectual disability have also been associated.	Rare genetic neurological disorder
Orphanet:320406	Spastic paraplegia-optic atrophy-neuropathy syndrome	FLRT1;KLC2	2	 gene (11q13.1), encoding kinesin light chain 2.	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:319547	Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiency	IFNGR2	1	Mendelian susceptibily to mycobacterial diseases (MSMD) due to complete interferon gamma receptor 2 (IFN-gammaR2) deficiency is a genetic variant of MSMD (see this term) characterized by a complete deficiency in IFN-gammaR2, leading to an undetectable response to IFN-gamma, and consequently, to severe and often fatal infections with bacillus Calmette-Guérin (BCG) and other environmental mycobacteria (EM).	Rare genetic immune disease
Orphanet:319519	Combined oxidative phosphorylation defect type 14	FARS2	1	Combined oxidative phosphorylation defect type 14 is a rare mitochondrial disease due to a defect in mitochondrial protein synthesis characterized by neonatal or infancy-onset of seizures that are refractory to treatment, delayed or absent psychomotor development and lactic acidosis. Additional manifestations reported include poor feeding, failure to thrive, microcephaly, hypotonia, anemia and thrombocytopenia.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:319524	Combined oxidative phosphorylation defect type 15	MTFMT	1	Combined oxidative phosphorylation defect type 15 is a rare mitochondrial disease due to a defect in mitochondrial protein synthesis characterized by onset in infancy or early childhood of muscular hypotonia, gait ataxia, mild bilateral pyramidal tract signs, developmental delay (affecting mostly speech and coordination) and subsequent intellectual disability. Short stature, obesity, microcephaly, strabismus, nystagmus, reduced visual acuity, lactic acidosis, and a brain neuropathology consistent with Leigh syndrome are also reported.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:319509	Combined oxidative phosphorylation defect type 9	MRPL3	1	Combined oxidative phosphorylation defect type 9 is a rare mitochondrial disease due to a defect in mitochondrial protein synthesis characterized by initially normal growth and development followed by the infantile-onset of failure to thrive, psychomotor delay, poor feeding, dyspnea, severe hypertrophic cardiomyopathy and hepatomegaly. Laboratory studies report increased plasma lactate and alanine, abnormal liver enzymes and decreased activity of mitochondrial respiratory chain complexes I, III, IV, and V.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:319514	Combined oxidative phosphorylation defect type 13	PNPT1	1	Combined oxidative phosphorylation defect type 13 is a rare mitochondrial disease due to a defect in mitochondrial protein synthesis characterized by normal early development followed by the sudden onset in infancy of poor feeding, dysphagia, truncal (followed by global) hypotonia, motor regression, abnormal movements (i.e. severe dystonia of limbs, choreoathetosis, facial dyskinesias) and reduced tendon reflexes. The disease course is severe but nonprogressive.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:319589	Autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency	IFNGR2	1	A rare, genetic variant of mendelian susceptibility to mycobacterial diseases (MSMD) characterized by a partial deficiency in IFN-gammaR2, leading to impaired response to IFN-gamma and, consequently, to recurrent, moderately severe infections with bacillus Calmette-Guérin (BCG) and other environmental mycobacteria (EM).	Rare genetic immune disease
Orphanet:319595	Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency	STAT1	1	Mendelian susceptibility to mycobacterial diseases (MSMD) due to partial STAT1 (signal transducer and activator of transcription 1) deficiency is a genetic variant of MSMD (see this term) characterized by a partial defect in the interferon (IFN)-gamma pathway, leading to mild mycobacterial infections.	Rare genetic immune disease
Orphanet:319574	Autosomal recessive mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency	IFNGR2	1	Autosomal recessive mendelian susceptibility to mycobacterial diseases (MSMD) due to partial IFNgammaR2 deficiency is a genetic variant of MSMD (see this term) characterized by a partial deficiency in IFN-gammaR2, leading to a residual response to IFN-gamma and consequently to recurrent, moderately severe infections with bacillus Calmette-Guérin (BCG) and other environmental mycobacteria (EM).	Rare genetic immune disease
Orphanet:319581	Autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency	IFNGR1	1	A rare, genetic variant of mendelian susceptibility to mycobacterial diseases (MSMD) characterized by a partial deficiency leading to impaired IFN-gamma immunity and, consequently, recurrent, moderately severe infections with bacillus Calmette-Guérin (BCG) and other environmental mycobacteria (EM).	Rare genetic immune disease
Orphanet:319563	Mendelian susceptibility to mycobacterial diseases due to complete ISG15 deficiency	ISG15	1	Mendelian susceptibility to mycobacterial diseases (MSMD) due to complete ISG15 deficiency is a genetic variant of MSMD (see this term) characterized by Bacille Calmette-Guérin (BCG) infections.	Rare genetic systemic or rheumatologic disease;Rare genetic immune disease
Orphanet:319569	Autosomal recessive mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency	IFNGR1	1	A genetic variant of mendelian susceptibility to mycobacterial diseases (MSMD) characterized by a partial deficiency in IFN-gammaR1, leading to a residual response to IFN-gamma and, consequently, to recurrent, moderately severe infections with bacillus Calmette-Guérin (BCG) and other environmental mycobacteria (EM).	Rare genetic immune disease
Orphanet:319552	Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency	IL12RB1	1	 infections.	Rare genetic immune disease
Orphanet:319558	Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency	IL12B	1	 infections.	Rare genetic immune disease
Orphanet:319651	Constitutional megaloblastic anemia with severe neurologic disease	DHFR	1	NA	Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic hematologic disease
Orphanet:319646	PGM1-CDG	PGM1	1	A rare, genetic, congenital disorder of glycosylation and glycogen storage disease characterized by a wide range of clinical manifestations, most commonly presenting with bifid uvula with or without cleft palate at birth, associated with growth delay, hepatopathy with elevated aminotransferase serum levels, myopathy (including exercise-related fatigue, exercise intolerance, muscle weakness), intermittent hypoglycemia, and dilated cardiomyopathy and/or cardiac arrest, due to decreased phosphoglucomutase 1 enzyme activity. Less common manifestations include malignant hyperthermia, rhabdomyolysis, and hypogonadotropic hypogonadism with delayed puberty.	Rare inborn errors of metabolism;Rare genetic hepatic disease;Rare genetic cardiac disease
Orphanet:319640	Retinal macular dystrophy type 2	PROM1	1	Retinal macular dystrophy type 2 is a rare, genetic macular dystrophy disorder characterized by slowly progressive ''bull's eye'' maculopathy associated, in most cases, with mild decrease in visual acuity and central scotomata. Usually, only the central retina is involved, however some cases of more widespread rod and cone anomalies have been reported. Rare additional features include empty sella turcica, impaired olfaction, renal infections, hematuria and recurrent miscarriages.	Rare genetic eye disease
Orphanet:319635	Amyloidosis cutis dyschromia	GPNMB	1	A rare primary cutaneous amyloidosis characterized by macular or reticulate hyperpigmentation with symmetrically distributed guttate hypo- and hyperpigmented lesions which progress gradually over the years to involve almost the entire body (with relative sparing of the face, hands, feet and neck). Patients are usually asymptomatic, however mild pruritus may be associated. Amyloid deposition in the papillary dermis is observed on skin biopsy. Systemic amyloidosis is not present and association with generalized morphea, atypical Parkinsonism, spasticity, motor weakness or colon carcinoma is rare.	
Orphanet:319623	X-linked mendelian susceptibility to mycobacterial diseases due to CYBB deficiency	CYBB	1	NA	Rare genetic immune disease
Orphanet:319612	X-linked mendelian susceptibility to mycobacterial diseases due to IKBKG deficiency	IKBKG	1	NA	Rare genetic immune disease
Orphanet:319600	Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency	IRF8	1	Mendelian susceptibility to mycobacterial diseases (MSMD) due to partial IRF8 (interferon regulatory factor 8) deficiency is a rare genetic variant of MSMD (see this term) characterized by a selective susceptibility to relatively mild infections with bacillus Calmette-Guérin (BCG)..	Rare genetic immune disease
Orphanet:319678	Encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome	COQ9	1	Encephalopathy-hypertrophic cardiomyopathy-renal tubular disease syndrome is a rare mitochondrial disease due to a defect in coenzyme Q10 biosynthesis that manifests with a broad spectrum of signs and symptoms which may include: neonatal lactic acidosis, global developmental delay, tonus disorder, seizures, reduced spontaneous movements, ventricular hypertrophy, bradycardia, renal tubular dysfunction with massive lactic acid excretion in urine, severe biochemical defect of respiratory chain complexes II/III when assayed together and deficiency of coenzyme Q10 in skeletal muscle. Cerebral and cerebellar atrophy can be seen on magnetic resonance imaging and multiple choroid plexus cysts and symmetrical hyperechoic signal alterations in basal ganglia have been observed on ultrasound.	Rare genetic cardiac disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:319675	Microcephalic primordial dwarfism, Dauber type	NIN	1	Microcephalic primordial dwarfism, Dauber type is a rare, genetic developmental defect during embryogenesis characterized by severe pre- and postnatal growth retardation, severe microcephaly, severe developmental delay and intelletual disability, severe adult short stature and facial dysmorphism (incl. hypotelorism, small ears, prominent nose). Other reported features include skeletal anomalies (Madelung deformity, clinodactyly, mild lumbar scoliosis, bilateral hip dysplasia) and seizures. Absence of thelarche and menarche is also associated.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:319671	Microcephalic primordial dwarfism, Alazami type	LARP7	1	Microcephalic primordial dwarfism, Alazami type is a rare, genetic developmental defect during embryogenesis syndrome characterized by severe intellectual disability, distinct dysmorphic facial features (i.e. triangular face with prominent forehead, narrow palpebral fissures, deep-set eyes, low-set ears, broad nose, malar hypoplasia, short philtrum, macrostomia, widely spaced teeth) and pre and postnatal proportionate short stature, ranging from primordial dwarfism (height below -3.5 SD) to a milder phenotype with less severe growth restriction (height below -2.5 SD). Other reported features include skeletal findings (e.g. scoliosis), microcephaly, involuntary hand movements, hypersensitivity to stimuli and behavioral problems, such as anxiety.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:319269	NA	CCR5	1	NA	NA
Orphanet:319276	Clear cell renal carcinoma	TMEM127	1	A rare renal tumor arising from proximal tubular epithelial cells of the renal cortex, characterized histologically by malignant epithelial cells with typical clear cytoplasm in conventional staining methods due to a high glycogen and lipid content, featuring a nested growth pattern. Clinically it may present with hematuria, flank pain, anemia or, less commonly, a palpable abdominal mass.	
Orphanet:319298	Papillary renal cell carcinoma	MET;MITF	2	Papillary renal cell carcinoma is a rare subtype of renal cell carcinoma, arising from the renal tubular epithelium and showing a papillary growth pattern, which typically manifests with hematuria, flank pain, palpable abdominal mass or nonspecific symptoms, such as fatigue, weight loss or fever. Symptoms related to metastatic spread, such as bone pain or persistent cough, are frequently associated since early diagnosis is not common. It is typically multifocal, bilateral, and in most cases sporadic, although different hereditary syndromes, such as Hereditary leiomyoma renal cell carcinoma, Birt-Hogg-Dubé syndrome and Tuberous sclerosis, may predispose to the development of papillary renal cell carcinoma.	
Orphanet:319303	Chromophobe renal cell carcinoma	HNF1A	1	Chromophobe renal cell carcinoma is a rare subtype of renal cell carcinoma, originating from the intercalating cells of the collecting ducts and macroscopically manifesting as a well-circumscribed, highly lobulated, solid tumor that is usually diagnosed at an early stage. It is frequently asymptomatic, or may present with nonspecific symptoms, such as weight loss, fever or fatigue. The classic presentation observed in renal tumors (hematuria, flank pain and palpable mass) is occasionally observed and usually indicates an advanced stage of the disease. It is most frequently sporadic however, several familial cases, associated with Birt-Hogg Dubé syndrome, have been described.	
Orphanet:319308	MiT family translocation renal cell carcinoma	PRCC;TFE3;ASPSCR1;TFEB;CLTC;SFPQ;NONO	7	and include hematuria, flank pain, palpable abdominal mass and/or systemic symptoms of anemia, fatigue and fever.	
Orphanet:319332	Autosomal recessive myogenic arthrogryposis multiplex congenita	SYNE1	1	Autosomal recessive myogenic arthrogryposis multiplex congenita is a rare inherited neuromuscular disease characterized by prenatal presentation (usually in the second trimester) of reduced fetal movements and abnormal positioning resulting in joint abnormalities that may involve both lower and upper extremities and is usually symmetric, severe hypotonia at birth with bilateral club foot, motor development delay, mild facial weakness without opthalmoplegia, absent deep tendon reflexes, normal motor and sensory nerve conduction velocities, no cerebellar or pyramidal involvement, and progressive disease course with loss of ambulation after the first decade of life.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:319340	Carney complex-trismus-pseudocamptodactyly syndrome	MYH8	1	Carney complex-trismus-pseudocamptodactyly syndrome is a rare genetic heart-hand syndrome characterized by typical manifestations of the Carney complex (spotty pigmentation of the skin, familial cardiac and cutaneous myxomas and endocrinopathy) associated with trismus and distal arthrogryposis (presenting as involuntary contraction of distal and proximal interphalangeal joints of hands evident only on dorsiflexion of wrist and similar lower-limb contractures producing foot deformities).	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic tumor
Orphanet:319487	Familial papillary or follicular thyroid carcinoma	MINPP1;FOXE1;HABP2	3	Familial papillary or follicular thyroid carcinoma is a rare, hereditary nonmedullary thyroid carcinoma characterized by the presence of differentiated thyroid cancer of follicular cell origin in two or more first-degree relatives, in the absence of other familial tumor syndromes or radiation exposure. Frequent capsular invasion is observed. Biopsy reveals multicentric tumors with multiple adenomatous nodules with or without oxyphilia and follicular or papillary carcinoma histology.	Rare genetic tumor
Orphanet:319480	Acute myeloid leukemia with CEBPA somatic mutations	CEBPA	1	 gene in the bone marrow, blood and, rarely, other tissues. It can present with anemia, thrombocytopenia, and other nonspecific symptoms related to ineffective hematopoesis (fatigue, bleeding and bruising, recurrent infections, bone pain) and/or extramedullary site involvement (gingivitis, splenomegaly).	Rare genetic tumor
Orphanet:319504	Combined oxidative phosphorylation defect type 8	AARS2	1	Combined oxidative phosphorylation defect type 8 is a mitochondrial disease due to a defect in mitochondrial protein synthesis resulting in deficiency of respiratory chain complexes I, III and IV in the cardiac and skeletal muscle and brain characterized by severe hypertrophic cardiomyopathy, pulmonary hypoplasia, generalized muscle weakness and neurological involvement.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:319465	Inherited acute myeloid leukemia	CEBPA;TGM6;GATA2	3	Inherited acute myeloid leukemia (AML) is a rare, malignant hematopologic disease characterized by clonal proliferation of myeloid blasts, primarily involving the bone marrow, in association with congenital disorders (e.g. Fanconi anemia, dyskeratosis congenita, Bloom syndrome, Down syndrome, congenital neutropenia, neurofibromatosis, etc.) and genetic defects predisposing to AML. Patients present with signs and symptoms related to ineffective hematopoesis (fatigue, bleeding and bruising, recurrent infections, bone pain) and/or extramedullary site involvement (gingivitis, splenomegaly, etc.). Depending on the underlying genetic defect, there may be additional cancer risks and other health problems present.	Rare genetic tumor
Orphanet:319462	Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations	BRCA2	1	Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations is a rare cancer-predisposing syndrome, associated with the D1 subgroup of Fanconi anemia (FA), characterized by progressive bone marrow failure, cardiac, brain, intestinal or skeletal abnormalities and predisposition to various malignancies. Bone marrow suppression and the incidence of developmental abnormalities are less frequent than in other FA, but cancer risk is very high with the spectrum of childhood cancers including Wilms tumor, brain tumor (often medulloblastoma) and ALL/AML.	Inherited cancer-predisposing syndrome
Orphanet:319199	Autosomal recessive spastic paraplegia type 53	VPS37A	1	 gene (8p22) encoding vacuolar protein sorting-associated protein 37A.	Rare genetic neurological disorder
Orphanet:319160	Congenital myopathy with internal nuclei and atypical cores	CCDC78	1	Congenital myopathy with internal nuclei and atypical cores is a rare genetic skeletal muscle disease characterized by neonatal hypotonia, distal more than proximal muscle weakness, progressive exercise intolerance with prominent myalgias, and mild-to-moderate overall motor impairment with preserved ambulation. Face, extraocular, cardiac, and respiratory muscles are unaffected. Mild cognitive impairment is also noted in most patients.	Rare genetic neurological disorder
Orphanet:319189	Familial cortical myoclonus	NOL3	1	Familial cortical myoclonus is a rare, genetic movement disorder characterized by autosomal dominant, adult-onset, slowly progressive, multifocal, cortical myoclonus. Patients present somatosensory-evoked, brief, jerky, involuntary movements in the face, arms and legs, associated in most cases with sustained, multiple, sudden falls without loss of consciousness. Seizures or other neurological deficits, aside from mild cerebellar ataxia late in the course of the illness, are absent.	Rare genetic neurological disorder
Orphanet:319182	Wiedemann-Steiner syndrome	SMC1A;KMT2A	2	Wiedemann-Steiner syndrome is a rare, genetic multiple congenital anomalies/dysmorphic syndrome characterized by short stature, hypertrichosis cubiti, facial dysmorphism (hypertelorism, long eyelashes, thick eyebrows, downslanted, vertically narrow, long palpebral fissures, wide nasal bridge, broad nasal tip, long philtrum), developmental delay, and mild to moderate intellectual disability. It has a variable clinical phenotype with additional manifestations reported including muscular hypotonia, patent ductus arteriosus, small hands and feet, hypertrichosis on the back, behavioral difficulties, and seizures.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:317428	Combined immunodeficiency due to ORAI1 deficiency	ORAI1	1	 deficiency is a form of CID due to Calcium release activated Ca2+ (CRAC) channel dysfunction (see this term) characterized by recurrent infections, congenital myopathy, ectodermal dysplasia and anhydrosis.	Rare genetic immune disease
Orphanet:317425	Severe combined immunodeficiency due to DNA-PKcs deficiency	PRKDC	1	Severe combined immunodeficiency (SCID) due to DNA-PKcs deficiency is an extremely rare type of SCID (see this term) characterized by the classical signs of SCID (severe and recurrent infections, diarrhea, failure to thrive), absence of T and B lymphocytes, and cell sensitivity to ionizing radiation.	Rare genetic immune disease
Orphanet:317430	Combined immunodeficiency due to STIM1 deficiency	STIM1	1	 deficiency is a form of CID due to Calcium release activated Ca2+(CRAC) channel dysfunction (see this term) characterized by recurrent infections, autoimmunity, congenital myopathy and ectodermal dysplasia.	Rare genetic immune disease
Orphanet:317473	Pancytopenia due to IKZF1 mutations	IKZF1	1	A rare syndrome with combined immunodeficiency characterized by a variable clinical presentation ranging from asymptomatic individuals to potentially life-threatening, recurrent bacterial infections associated with progressive loss of serum immunoglobulins and B cells.	Rare genetic immune disease
Orphanet:317476	X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia	MAGT1	1	X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia is a rare combined T and B cell immunodeficiency characterized by recurrent sinopulmonary and viral infections, persistent elevated Epstein-Barr virus (EBV) viremia and increased susceptibility to EBV-associated B-cell lymphoproliferative disorders. Immunological analyses show normal lymphocyte count or mild to moderate lymphopenia, inverted CD4:CD8 T-cell ratio and hypogammaglobulinemias.	Rare genetic immune disease
Orphanet:315311	Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, simple virilizing form	CYP21A2	1	The simple virilizing form of classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency (classical 21 OHD CAH; see this term) is characterized by genital ambiguity and virilization of the external genitalia in females, hypocortisolism and precocious pseudopuberty without salt-wasting.	Genetic infertility;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease;Rare genetic gynecological and obstetrical diseases
Orphanet:315306	Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, salt wasting form	CYP21A2	1	The salt wasting form of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (classical 21 OHD CAH; see this term) is characterized by virilization of the external genitalia in females, hypocortisolism, precocious pseudopuberty and renal salt loss due to aldosterone deficiency.	Genetic infertility;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease;Rare genetic gynecological and obstetrical diseases
Orphanet:314978	X-linked non progressive cerebellar ataxia	ATP2B3	1	X-linked non progressive cerebellar ataxia is a rare hereditary ataxia characterized by delayed early motor development, severe neonatal hypotonia, non-progressive ataxia and slow eye movements, presenting normal cognitive abilities and absence of pyramidal signs. Frequently patients also manifest intention tremor, mild dysphagia, and dysarthria. Brain MRI reveals global cerebellar atrophy with absence of other malformations or degenerations of the central and peripheral nervous systems.	Rare genetic neurological disorder
Orphanet:314950	Primary hypereosinophilic syndrome	FGFR1;FIP1L1;PDGFRA;PDGFRB;ETV6	5	NA	
Orphanet:314918	Mild Canavan disease	ASPA	1	Mild Canavan disease (CD) is a neurodegenerative disorder characterized by mild speech delay or motor development.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:314911	Severe Canavan disease	ASPA	1	Severe Canavan disease (CD) is a rapidly progressing neurodegenerative disorder characterized by leukodystrophy with macrocephaly, severe developmental delay and hypotonia.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:314679	Cerebrofacioarticular syndrome	DCHS1;FAT4	2	Cerebrofacioarticular syndrome is a rare multiple congenital anomalies syndrome characterized by mild to severe intellectual disability, a distinctive facial gestalt (blepharophimosis, maxillary hypoplasia, telecanthus, microtia and atresia of the external auditory meatus) as well as skeletal and articular abnormalities (e.g. camptodactyly of the fingers, cutaneous syndactyly, talipes equinovarus, flexion contractures of the proximal interphalangeal joints, hip or elbow subluxation, joint laxity). Affected individuals also present neonatal hypotonia, variable respiratory manifestations, chronic feeding difficulties and gray matter heterotopia.	Rare genetic developmental defect during embryogenesis
Orphanet:314667	TMEM165-CDG	TMEM165	1	 (4q12).	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic hepatic disease;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:314689	Combined immunodeficiency due to STK4 deficiency	STK4	1	A rare, genetic, combined T and B cell immunodeficiency characterized by T- and B-cell lymphopenia, hypergammaglobulinemia and intermittent neutropenia. It presents with recurrent opportunistic viral, bacterial and fungal infections involving skin (cutaneous papillomatosis, molluscum contagiosum, skin abscesses, mucocutaneous candidiasis), upper and lower respiratory tract or septicemia. Other clinical features include autoimmune manifestations (autoimmune hemolytic anemia) and congenital heart defects (atrial septal defects, patent foramen ovale, mitral, triscupid and pulmonary valve insufficiency).	Rare genetic immune disease
Orphanet:314652	Variant ABeta2M amyloidosis	B2M	1	A rare form of amyloidosis characterized by accumulation and extensive visceral deposition of anamyloidogenic variant of beta 2 microglobulin leading to progressive gastrointestinal dysfunction, Sjögren syndrome and autonomic neuropathy.	Rare genetic systemic or rheumatologic disease
Orphanet:314647	Non-progressive cerebellar ataxia with intellectual disability	CAMTA1	1	Non-progressive cerebellar ataxia with intellectual deficit is a rare subtype of autosomal dominant cerebellar ataxia type 1 (ADCA type 1; see this term) characterized by the onset in infancy of cerebellar ataxia, neonatal hypotonia (in some), mild developmental delay and, in later life, intellectual disability. Less common features include dysarthria, dysmetria and dysmorphic facial features (long face, bulbous nose long philtrum, thick lower lip and pointed chin).	Rare genetic neurological disorder
Orphanet:314662	Segmental progressive overgrowth syndrome with fibroadipose hyperplasia	PIK3CA	1	A rare PIK3CA-related overgrowth syndrome disease characterized by segmental and progressive overgrowth, predominantly involving the adipose tissue, or a mixture of adipose and fibrous tissue, with variable involvement of subcutaneous and muscular tissue, as well as skeletal overgrowth. Overgrowth severity and range is highly variable, although frequently it is asymmetric and disproportionate, it affects lower extremities more than the upper ones, and progresses in a distal to proximal patten. Congenital overgrowth is typically associated.	Rare genetic developmental defect during embryogenesis
Orphanet:314655	Severe neonatal hypotonia-seizures-encephalopathy syndrome due to 5q31.3 microdeletion	PURA	1	NA	Rare genetic developmental defect during embryogenesis;Rare chromosomal anomaly
Orphanet:314629	CLN11 disease	GRN	1	NA	Rare genetic eye disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:314637	Mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency	MTO1	1	A rare mitochondrial oxidative phosphorylation disorder with complex I and IV deficiency characterized by lactic acidosis, hypotonia, hypertrophic cardiomyopathy and global developmental delay. Other clinical features include feeding difficulties, failure to thrive, seizures, optic atrophy and ataxia.	Rare genetic cardiac disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:314632	ATP13A2-related juvenile neuronal ceroid lipofuscinosis	ATP13A2	1	A rare neuronal ceroid lipofiscinosis disorder characterized by juvenile-onset of progressive spinocerebellar ataxia, bulbar syndrome (manifesting with dysarthria, dysphagia and dysphonia), pyramidal and extrapyramidal involvement (including myoclonus, amyotrophy, unsteady gait, akinesia, rigidity, dysarthric speech) and intellectual deterioration. Muscle biopsy displays autofluorescent bodies and lipofuscin deposits in brain and, occasionally the retina, upon post mortem.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:314802	Short stature due to partial GHR deficiency	GHR	1	Short stature due to partial GHR deficiency is a rare, genetic, endocrine disease characterized by idiopathic short stature due to diminished GHR function (decreased ligand binding or reduced availability of receptor), thus resulting in partial insensitivity to growth hormone.	Rare genetic endocrine disease
Orphanet:314811	Short stature due to GHSR deficiency	GHSR	1	Short stature due to GHSR deficiency is a rare, genetic, endocrine growth disease, resulting from growth hormone secretagogue receptor (GHSR) deficiency, characterized by postnatal growth delay that results in short stature (less than -2 SD). The pituitary gland is typically without morphological changes, although anterior pituitary gland hypoplasia has been reported.	Rare genetic endocrine disease
Orphanet:314777	Familial isolated pituitary adenoma	CDH23;AIP	2	A rare, hereditary endocrine tumor characterized by a benign pituitary adenoma that is either secreting (e.g. prolactin, growth hormone, thyroid stimulating hormone) or non-secreting. Symptoms may occur due to either the hormonal hypersecretion and/or the mass effect of the lesion on local structures in the brain.	Rare genetic endocrine disease
Orphanet:314786	Silent pituitary adenoma	MEN1;AIP	2	NA	Rare genetic endocrine disease
Orphanet:314790	Null pituitary adenoma	MEN1;AIP	2	NA	Rare genetic endocrine disease
Orphanet:314795	SHOX-related short stature	SHOX	1	SHOX-related short stature is a primary bone dysplasia characterized by a height that is 2 standard deviations below the corresponding mean height for a given age, sex and population group, in the absence of obvious skeletal abnormalities and other diseases and with normal developmental milestones. Patients present normal bone age with normal limbs, shortening of the extremities (significantly lower extremities-trunk and sitting height-to-height ratios), normal hGH values, normal karyotype, and Leri-Weill dyschondrosteosis-like radiological signs (e.g. triangularization of distal radial epiphyses, pyramidalization of distal carpal row, and lucency of the distal radius on the ulnar side). Mesomelic disproportions and Madelung deformity are not apparent at a young age, but may develop later in life or never.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:314718	Lethal arteriopathy syndrome due to fibulin-4 deficiency	EFEMP2	1	Lethal arteriopathy syndrome due to fibulin-4 deficiency is a rare, genetic, vascular disorder characterized by severe aneurysmal dilatation, elongation, and tortuosity of the thoracic aorta, its branches and pulmonary arteries with stenosis at various typical locations, typically resulting in infantile demise. Variable associated features may include cutis laxa, long philtrum with thin vermillion border, hypertelorism, sagging cheeks, arachnodactyly, joint laxity and pectus deformities.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:314721	Atypical dentin dysplasia due to SMOC2 deficiency	SMOC2	1	A rare, genetic, dentin dysplasia disease characterized by extreme microdontia, oligodontia, and abnormal tooth shape (including globular teeth, incisal notches and double tooth formation). Short roots with a variable pulp phenotype (including taurodontia and flame-shaped pulp), enamel hypoplasia and anterior open bite may also be associated.	Rare genetic odontologic disease
Orphanet:370114	Combined cervical dystonia	ATM	1	NA	NA
Orphanet:370109	Ataxia-telangiectasia variant	ATM	1	A rare, genetic, persistent combined dystonia characterized by clinical signs similar to ataxia-telangiectasia but with a later (usually adulthood) onset and slower progression. Patients typically present extrapyramidal signs, such as resting tremor, choreathetosis, and dystonia, as the initial symptoms and later often develop mild cerebellar ataxia (with gait usually preserved). Telangiectasia and immunodeficiency may be absent but secondary features of ataxia-telangiectasia, such as risk of malignancy, dysarthria and peripheral neuropathy, are frequently present.	Rare genetic neurological disorder
Orphanet:370103	Primary dystonia, DYT17 type	DYT17	1	Primary dystonia, DYT17 type is a rare, genetic, isolated dystonia initially presenting as torticollis, and later progressing to segmental or generalized dystonia. Dysphonia and dysarthria also occur later in the disease course.	Rare genetic neurological disorder
Orphanet:370097	Oculocutaneous albinism type 6	SLC24A5	1	 gene (15q21.1).	Rare inborn errors of metabolism;Rare genetic eye disease;Rare genetic skin disease
Orphanet:370396	Small cell carcinoma of the ovary	SMARCA4	1	Small cell carcinoma of the ovary is a rare, highly aggressive, poorly differentiated ovarian neoplasm, often associated with paraneoplastic hypercalcemia. It is usually diagnosed in childhood or young adulthood at an advanced stage and presents with abdominal or pelvic mass or, rarely, symptoms related to hypercalcemia. Occasional familial cases have been reported.	
Orphanet:370348	Peripheral primitive neuroectodermal tumor	FLI1	1	A rare, aggressive, malignant, neoplastic disease characterized by a usually ill-defined, solid, multilobulated mass, frequently having necrosis, located on any site of the body (except the central nervous system), composed of small, round, poorly differentiated cells, with or without Homer-Wright rosettes, showing varying degrees of neuroectodermal differentiation. Manifestations are variable depending on location, with osteolytic destruction being common when arising from bone.	
Orphanet:370334	Extraskeletal Ewing sarcoma	ERG;EWSR1;FLI1;SMARCA5	4	Extraskeletal Ewing sarcoma is a rare, poorly differentiated, highly malignant, soft tissue tumor, derived from neuroectoderm, that is morphologically indistinguishable from skeletal Ewing sarcoma but is located in extraosseous locations, with the most common being: chest wall, paravertebral region, abdominopelvic area (with predilection for the retroperitoneal space), gluteal region and lower extremities. Clinical presentation is highly variable and depends on tumor localization. Local recurrence is common and metastatic disease most frequently involves the bones and lungs.	
Orphanet:370022	Ataxia-intellectual disability-oculomotor apraxia-cerebellar cysts syndrome	LAMA1	1	A rare neuro-ophthalmological disease characterized by nonprogressive cerebellar ataxia, delayed motor and language development and intellectual disability, in addition to ophthalmological abnormalities (e.g. oculomotor apraxia, strabismus, amblyopia, retinal dystrophy and myopia). Cerebellar cysts, cerebellar dysplasia and cerebellar vermis hypoplasia, seen on magnetic resonance imaging, are also characteristic of the disease.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:370026	Acute myeloid leukemia with t(8;16)(p11;p13) translocation	CREBBP;KAT6A	2	 or in therapy-related AML cases, and is characterized by frequent extramedullary involvement (mainly hepatomegaly, splenomegaly, lymphadenopathies, cutaneous infiltration, but also gum, bone, central nervous system, testicles involvement), severe coagulation disorder (disseminated intravascular coagulopathy or primary fibrinolysis) and poor prognosis. Morphologically, a blast population with a myelomonocytic stage of differentiation is observed.	
Orphanet:370088	Acute infantile liver failure-multisystemic involvement syndrome	LARS	1	A rare, genetic, parenchymal hepatic disease characterized by acute liver failure, that occurs in the first year of life, which manifests with failure to thrive, hypotonia, moderate global developmental delay, seizures, abnormal liver function tests, microcytic anemia and elevated serum lactate. Other associated features include hepatosteatosis and fibrosis, abnormal brain morphology, and renal tubulopathy. Minor illness exacerbates deterioration of liver failure.	Rare genetic hepatic disease
Orphanet:370997	Muscle-eye-brain disease with bilateral multicystic leucodystrophy	DAG1	1	A rare, genetic, congenital muscular alpha-dystroglycanopathy with brain and eye anomalies disease characterized by a severe muscle-eye-brain disease-like phenotype associated with intellectual disability, muscular dystrophy, macrocephaly and extended bilateral multicystic white matter disease.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:370921	STT3A-CDG	STT3A	1	 (11q23.3).	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:370924	STT3B-CDG	STT3B	1	 (3p24.1).	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:370927	SSR4-CDG	SSR4	1	 (Xq28).	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:370930	XYLT1-CDG	XYLT1	1	XYLT1-CDG is a rare congenital disorder of glycosylation characterized by moderate intellectual disability, short stature, mild skeletal changes and distinctive facial features with coarse face, synophyrs and deep nasolabial ridges. Skeletal features include broad ribs, stocky long bones, short femoral necks with coxa valga, clinodactyly and broad thumbs.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:370959	Congenital muscular dystrophy with cerebellar involvement	POMGNT1;POMT1;POMT2;FKRP;POMK;GMPPB	6	Congenital muscular dystrophy with cerebellar involvement is a rare, congenital muscular dystrophy due to dystroglycanopathy characterized by proximal muscule weakness with a tendency for muscle hypertrophy and pseudohypertrophy, variable cognitive impairment, microcephaly, cerebellar hypoplasia with or without cysts, and other structural brain anomalies.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:370968	Congenital muscular dystrophy with intellectual disability	POMT1;POMT2;FKRP;LARGE1;GMPPB	5	Congenital muscular dystrophy with intellectual disability is a rare, genetic, congenital muscular dystrophy due to dystroglycanopathy disorder characterized by a wide phenotypic spectrum which includes hypotonia and muscular weakness present at birth or early infancy and delayed or arrested motor development, associated with mild to severe intellectual disability and variable brain abnormalities on neuroimaging studies. Feeding difficulties, joint and spinal deformities, respiratory insufficiency, and ocular anomalies (e.g. strabismus, retinal dystrophy, oculomotor apraxia) may be associated. Decreased or absent alpha-dystroglycan on immunohistochemical muscle staining and elevated serum creatine kinase are observed.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:370980	Congenital muscular dystrophy without intellectual disability	POMT1;FKTN;FKRP;ISPD	4	Congenital muscular dystrophy without intellectual disability is a rare, genetic, congenital muscular dystrophy due to dystroglycanopathy disorder characterized by a wide phenotypic spectrum which includes hypotonia and muscular weakness present at birth or early infancy, delayed or arrested motor development, and normal intellectual abilities with normal (or only mild abnormalities) neuroimaging studies. Feeding difficulties, joint and spinal deformities, and respiratory insufficiency may be associated. Decreased alpha-dystroglycan on immunohistochemical muscle staining and elevated serum creatine kinase are observed.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:370938	Salt-and-pepper syndrome	ST3GAL5	1	A rare, genetic, congenital disorder of glycosylation with neurological involvement disorder characterized by the association of severe intellectual disability with altered dermal pigmentation (scattered hyper-and hypo-pigmented macules ranging from 1 to 5 mm on the face, trunk and extremities). Additional variable manifestations include scoliosis, choreoathetosis, seizures, spasticity and nonspecific abnormal electrocardiogram. Reported facial dysmorphism includes microcephaly, midface hypoplasia, and prominent lower face. Radiographic examination shows decreased bone mineralization.	Rare genetic skin disease;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:370943	Autism spectrum disorder-epilepsy-arthrogryposis syndrome	SLC35A3	1	 (1p21).	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:369929	Primary hyperaldosteronism-seizures-neurological abnormalities syndrome	CACNA1D	1	A rare, genetic, neurologic disease characterized by primary hyperaldosteronism presenting with early-onset, severe hypertension, hypokalemia and neurological manifestations (including seizures, severe hypotonia, spasticity, cerebral palsy and profound developmental delay/intellectual disability).	Rare genetic endocrine disease
Orphanet:369920	Pontocerebellar hypoplasia type 9	AMPD2	1	Pontocerebellar hypoplasia type 9 is a rare, genetic, subtype of non-syndromic pontocerebellar hypoplasia characterized by progressive cerebellum and brainstem atrophy, corpus callosum hypo-/aplasia and progressive post-natal microcephaly. Patients typically present profound global developmental delay, spastic tetraparesis, seizures, cortical visual impairment and, on neuroimaging, abnormal brain morphology that includes pontocerebellar hypoplasia, ''figure of 8'' midbrain appearance, and, more variably, interhemispheric cysts, ventriculomegaly and cerebral dysmyelination.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:369942	CADDS	ABCD1;BCAP31	2	CADDS is a rare, genetic, neurometabolic disease characterized by severe intrauterine growth retardation, failure to thrive, profound neonatal hypotonia, severe global development delay, elevated very long chain fatty acids in plasma, and neonatal cholestasis leading to hepatic failure and death. Other features include ocular abnormalities (e.g. blindness and cataracts), sensorineural deafness, seizures, and abnormal brain morphology (notably delayed CNS myelination and ventriculomegaly).	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic hepatic disease;Rare inborn errors of metabolism
Orphanet:369939	Severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome	BCAP31	1	A rare, genetic, neurological disorder characterized by intrauterine growth retardation, failure to thrive, infantile onset of sensorineural deafness, severe global developmental delay or absent psychomotor development, paraplegia or quadriplegia with dystonia and pyramidal signs, microcephaly, ocular abnormalities (strabismus, optic atrophy), mildly dysmorphic features (deep-set eyes, prominent nasal bridge, micrognathia), seizures and abnormalities of brain morphology (hypomyelinating white matter changes, cerebral atrophy).	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder
Orphanet:369955	Methylmalonic acidemia with homocystinuria, type cblJ	ABCD4	1	NA	Rare inborn errors of metabolism;Rare genetic hematologic disease
Orphanet:369970	Microcornea-myopic chorioretinal atrophy-telecanthus syndrome	ADAMTS18	1	Microcornea-myopic chorioretinal atrophy-telecanthus syndrome is rare, genetic, developmental defect of the eye disease characterized by childhood onset of mild to severe myopia with microcornea and chorioretinal atrophy, typically associated with telecanthus and posteriorly rotated ears. Other variable features include early-onset cataracts, ectopia lentis, ecotpia pupilae and retinal detachment.	Rare genetic eye disease
Orphanet:369962	Methylmalonic acidemia with homocystinuria, type cblX	HCFC1	1	NA	Rare inborn errors of metabolism;Rare genetic hematologic disease
Orphanet:369992	Severe dermatitis-multiple allergies-metabolic wasting syndrome	DSP;DSG1	2	Severe dermatitis-multiple allergies-metabolic wasting syndrome is a rare, genetic, epidermal disorder characterized by congenital erythroderma with severe psoriasiform dermatitis, ichthyosis, severe palmoplantar keratoderma, yellow keratosis on the hands and feet, elevated immunoglobulin E, multiple food allergies, and metabolic wasting. Other variable features may include hypotrichosis, nail dystrophy, recurrent infections, mild global developmental delay, eosinophillia, nystagmus, growth impairment and cardiac defects.	Rare genetic immune disease;Rare genetic skin disease
Orphanet:370002	Focal palmoplantar keratoderma with joint keratoses	DSG1	1	Focal palmoplantar keratoderma with joint keratoses is a rare, genetic, isolated palmoplantar keratoderma disorder characterized by focal hyperkeratotic lesions affecting the pressure- and mechanical trauma-bearing areas of the palms and soles, as well as hyperkeratotic plaques involving joints, including knees, elbows, ankles and dorsa of interphalangeal joints.	Rare genetic skin disease
Orphanet:369999	Diffuse palmoplantar keratoderma with painful fissures	DSG1	1	Diffuse palmoplantar keratoderma with painful fissures is a rare, genetic, isolated palmoplantar keratoderma disorder characterized by non-epidermolytic, diffuse hyperkeratotic lesions affecting both the palms and the soles, associated with a tendency of painful fissuring. Contrary to the clinical findings, histologic examination reveals findings suggestive of keratosis palmoplantaris striata, with orthohyperkeratosis featuring widening of the intercellular spaces and disadhesion of keratocytes in the upper epidermal layers.	Rare genetic skin disease
Orphanet:369837	Intellectual disability-seizures-hypophosphatasia-ophthalmic-skeletal anomalies syndrome	PIGT	1	Intellectual disability-seizures-hypotonia-ophthalmologic-skeletal anomalies syndrome is a rare congenital disorder of glycosylation characterized by neonatal hypotonia, global development delay, developmental regress and severe to profound intellectual disability, infantile onset seizures that are initially associated with febrile episodes with subsequent transition to unprovoked seizures, impaired vision with esotropia and nystagmus, progressive cerebral and cerebellar atrophy, skeletal abnormalities (including brachycephaly, scoliosis, slender long bones, delayed bone age, pectus excavatum and osteopenia), inverted nipples and dysmorphic features including high and narrow forehead, frontal bossing, short nose, depressed nasal bridge, anteverted nares, high palate and wide open mouth consistent with facial hypotonia. Other features may include cardiac abnormalities (such as patent ductus arteriosus, atrial septal defects), urogenital abnormalities (such as nephrocalcinosis, urolithiasis), and low plasma concentration of alkaline phosphatase.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare inborn errors of metabolism
Orphanet:369840	Autosomal recessive limb-girdle muscular dystrophy type 2S	TRAPPC11	1	A form of limb-girdle muscular dystrophy characterized by childhood-onset of progressive proximal muscle weakness (leading to reduced ambulation) with myalgia and fatigue, in addition to infantile hyperkinetic movements, truncal ataxia, and intellectual disability. Additional manifestations include scoliosis, hip dysplasia, and less commonly, ocular features (e.g. myopia, cataract) and seizures.	Rare genetic neurological disorder
Orphanet:369847	Intellectual disability-hyperkinetic movement-truncal ataxia syndrome	TRAPPC11	1	A rare, genetic, syndromic intellectual disability disease characterized by global developmental delay, microcephaly, mild to moderate intellectual disability, truncal ataxia, trunk and limb, or generalized, choreiform movements, and elevated serum creatine kinase levels. Variably associated features include mild cerebral atrophy, muscular weakness or hypotonia in early childhood, and/or seizures. Ocular abnormalities (e.g. exophoria, anisometropia, amblyopia) have been reported.	Rare genetic neurological disorder
Orphanet:369852	Congenital neutropenia-myelofibrosis-nephromegaly syndrome	VPS45;RBSN	2	Congenital neutropenia-myelofibrosis-nephromegaly syndrome is rare, genetic, primary immunodeficiency disorder characterized by severe congenital neutropenia, bone marrow fibrosis and neutrophil dysfunction which is refractory to granulocyte colony-stimulating factor, manifesting with life-threatening infections and/or deep-seated abscesses, hepato-/splenomegaly, thrombocytopenia, hypergammaglobulinemia, anemia with reticulocytosis and nephromegaly. Other reported features include osteosclerosis and neurological abnormalities (e.g. developmental delay, cortical blindness, hearing loss, thin corpus callosum or dysrhythima on EEG).	Rare genetic immune disease
Orphanet:369861	Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome	TRNT1	1	Congenital sideroblastic anemia -B cell immunodeficiency- periodic fever-developmental delay syndrome is a form of constitutional sideroblastic anemia (see this term), characterized by severe microcytic anemia, B-cell lymphopenia , panhypogammaglobulinemia and variable neurodegeneration. The disease presents in infancy with recurrent febrile illnesses, gastrointestinal disturbances, developmental delay, seizures, ataxia and sensorineural deafness. Most patients require regular blood transfusion, iron chelation, and intravenous immunoglobulin (IVIG) replacement. Stem cell transplantation has been reported to be successful.	Rare genetic immune disease;Rare genetic hematologic disease
Orphanet:369867	Autosomal recessive intermediate Charcot-Marie-Tooth disease type C	PLEKHG5	1	A rare subtype of autosomal recessive intermediate Charcot-Marie-Tooth (CMT) disease characterized by childhood to adulthood-onset of progressive, moderate to severe, predominantly distal, mostly lower limb muscle weakness and atrophy, foot deformities (including pes cavus and hammer toes), absent deep tendon reflexes and distal sensory loss associated with decreased motor and sensory nerve conduction velocities and features of both demyelinating and axonal neuropathy on sural nerve biopsy.	Rare genetic neurological disorder
Orphanet:369873	Obesity due to SIM1 deficiency	SIM1	1	A rare, genetic form of obesity characterized by severe early-onset obesity, hyperphagia, and variable presence of cognitive impairment and behavioral disorder, including autistic spectrum behavior, impaired concentration and memory deficit. Some patients present with Prader-Willi-like features such as hypotonia, developmental delay, intellectual disability, short stature, hypopituitarism and dysmorphic facial features.	Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease
Orphanet:369881	2p21 microdeletion syndrome without cystinuria	PREPL;CAMKMT	2	2p21 microdeletion syndrome without cystinuria is a rare partial autosomal monosomy characterized by weak fetal movements, severe infantile hypotonia and feeding difficulties that spontaneously improve with time, urogenital abnormalities (hypospadias or hypoplastic labia majora), global development delay, mild intellectual disability and facial dysmorphism (dolichocephaly, frontal bossing, bilateral ptosis, midface retrusion, open mouth with tented upper lip vermilion). Affected individuals have borderline elevated serum lactate but no cystinuria.	Rare chromosomal anomaly
Orphanet:369891	Developmental delay-facial dysmorphism syndrome due to MED13L deficiency	MED13L	1	A rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by varying degrees of intellectual disability, global developmental delay (notably with severe speech and language impairment), muscular hypotonia, and facial dysmorphism (i.e. broad forehead, bitemporal narrowing, upslanting palpebral fissures, low-set ears, flat nasal bridge, bulbous nose and, variably, macroglossia). Highly variable additional features include cardiac defects (including persistent foramen ovale, ventricular septal defects, tetralogy of Fallot), coordination problems, seizures, abnormal growth parameters (including microcephaly, low birth and postnatal weight), and brain morphology anomalies (such as ventriculomegaly and myelination defects).	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic cardiac disease
Orphanet:369897	Mitochondrial DNA depletion syndrome, encephalomyopathic form with variable craniofacial anomalies	FBXL4	1	NA	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic gastroenterological disease;Rare genetic neurological disorder
Orphanet:369913	Combined oxidative phosphorylation defect type 17	ELAC2	1	Combined oxidative phosphorylation defect type 17 is a rare, genetic, mitochondrial disorder due to a defect in mitochondrial protein synthesis characterized by infantile-onset of severe hypertrophic cardiomyopathy (that occasionally progresses to dilated cardiomyopathy) associated with failure to thrive, global development delay, muscular hypotonia, elevated serum lactate and complex I deficiency in skeletal muscle biopsy. Intellectual disability, pericardial effusion and a mild cardiac phenotype have been also reported.	Rare genetic cardiac disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:364063	Infantile epileptic-dyskinetic encephalopathy	ARX	1	A monogenic disease with epilepsy characterized by developmental delay and infantile spasms in the first months of life, followed by chorea and generalized dystonia and progressing to quadriplegic dyskinesia, recurrent status dystonicus, intractable focal epilepsy and severe intellectual disability.	Rare genetic neurological disorder
Orphanet:364055	Severe early-childhood-onset retinal dystrophy	RPE65;LCA5;LRAT;SPATA7	4	Severe early childhood onset retinal dystrophy (SECORD) is an inherited retinal dystrophy characterized by a severe congenital night blindness, progressive retinal dystrophy and nystagmus. Best corrected visual acuity can reach 0.3 in the first decade of life and can pertain well into the second decade of life. Blindness is often complete by the age of 30 years.	Rare genetic eye disease
Orphanet:364043	ALK-positive large B-cell lymphoma	ALK	1	A very rare variant of diffuse large B-cell lymphoma (DLBCL) mainly affecting middle-aged immunocompetent men and characterized by a consistent primary involvement of lymph nodes (mainly in the cervical and mediastinum lymph nodes) and with infrequent extra nodal involvement of the bone marrow and other extra-nodal sites (head and neck region, liver, spleen, and gastrointestinal tract). It has an aggressive disease course, and is associated with a poor prognosis.	
Orphanet:364028	X-linked intellectual disability due to GRIA3 mutations	GRIA3	1	A rare, genetic, X-linked syndromic intellectual disability disorder characterized by moderate to severe intellectual disability associated with epilepsy, short stature, autistic features and behavioral problems, such as self injury and aggressive outbursts. Observed facial dysmorphism includes brachycephaly, prominent supraorbital ridges, and deep set eyes. Additional variable manifestations include malposition of feet, asthenic habitus, hyporeflexia, bowel occlusions, hydronephrosis, ren arcuatus, delayed motor development and disturbed sleep-wake cycle.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:772	Infantile Refsum disease	PEX2;PEX1;PEX10;PEX12;PEX13;PEX14;PEX16;PEX19;PEX26;PEX3;PEX5;PEX6;PEX11B	13	Infantile Refsum disease (IRD) is the mildest variant of the peroxisome biogenesis disorders, Zellweger syndrome spectrum (PBD- ZSS; see this term), characterized by hypotonia, retinitis pigmentosa, developmental delay, sensorineural hearing loss and liver dysfunction. Phenotypic overlap is seen between IRD and neonatal adrenoleukodystrophy (NALD) (see this term).	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic hepatic disease;Rare inborn errors of metabolism
Orphanet:1194	TMEM70-related mitochondrial encephalo-cardio-myopathy	TMEM70	1	 mutation is characterized by early neonatal onset of hypotonia, hypetrophic cardiomyopathy and apneic spells within hours after birth accompanied by lactic acidosis, hyperammonemia and 3-methylglutaconic aciduria.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:1048	Isolated anencephaly/exencephaly	MTHFR;VANGL2	2	A neural tube defect. This malformation is characterized by the total or partial absence of the cranial vault and the covering skin, the brain being missing or reduced to a small mass. Most cases are stillborn, although some infants have been reported to survive for a few hours or even a few days.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:363989	Familial benign flecked retina	PLA2G5	1	Familial benign flecked retina is a rare retinal dystrophy characterized by diffuse bilateral white-yellow fleck-like lessions extending to the far periphery of the retina but sparing the foveal region, with asymptomatic clinical phenotype and absence of electrophysiologic deficits.	Rare genetic eye disease
Orphanet:363992	Ichthyosis-short stature-brachydactyly-microspherophakia syndrome	ADAMTS17;CERS3	2	A rare, syndromic ichthyosis characterized by a collodion membrane at birth, generalized congenital ichthyosis, microspherophakia, myopia, ectopia lentis, short stature with brachydactyly and joint stiffness, and occasionally mitral valve dysplasia.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic eye disease
Orphanet:363981	Charcot-Marie-Tooth disease type 4B3	SBF1	1	Charcot-Marie-Tooth disease type 4B3 (CMT4B3) is a subtype of Charcot-Marie-Tooth type 4 characterized by a childhood onset of slowly progressing, demyelinating sensorimotor neuropathy, focally folded myelin sheaths in nerve biopsy, reduced nerve conduction velocities (less than 38 m/s), and the typical CMT phenotype (i.e. distal muscle weakness and atrophy, and sensory loss).	Rare genetic neurological disorder
Orphanet:363969	Autosomal recessive cerebral atrophy	TMPRSS4	1	A rare, genetic, neurodegenerative disorder characterized by ventriculomegaly and progressive, symmetrical atrophy of the cerebral cortex grey and white matter (sparing the midbrain, brainstem, cerebellum and infratentorial segments), manifesting in early infancy with acquired microcephaly, irritability, regression of developmental milestones, feeding difficulties, akathisia, exaggerated startle response, spasticity (fisted hands, stiff arms, leg scissoring), abnormal muscle tone with hypotonic trunk and hypertonic extremities, visual impairment and seizures.	Rare genetic neurological disorder
Orphanet:363972	Noonan syndrome-like disorder with juvenile myelomonocytic leukemia	CBL	1	Noonan syndrome-like disorder with juvenile myelomonocytic leukemia is a rare, genetic, polymalformative syndrome with increased risk of developing cancer characterized by a Noonan-like phenotype, including typical dysmorphic facial features (i.e. high forehead, hypertelorism, downslanting palpebral fissures, ptosis, low-set ears, prominent philtrum and short neck with or without pterygium colli), thoracic abnormalities, congenital heart defects and short stature, associated with a very frequent ocurrence of juvenile myelomonocytic leukemia. Developmental delay, ectodermal anomalies, joint laxity, and hypotonia may also be associated.	Inherited cancer-predisposing syndrome;Rare genetic cardiac disease;Rare genetic neurological disorder;RASopathy;Rare genetic developmental defect during embryogenesis
Orphanet:363965	Koolen-De Vries syndrome due to a point mutation	KANSL1	1	NA	Rare genetic developmental defect during embryogenesis
Orphanet:363958	17q21.31 microdeletion syndrome	KANSL1	1	NA	Rare chromosomal anomaly;Rare genetic developmental defect during embryogenesis
Orphanet:363727	X-linked dyserythropoietic anemia with abnormal platelets and neutropenia	GATA1	1	X-linked dyserythropoietic anemia with abnormal platelets and neutropenia is a rare, genetic, constitutional dyserythropoietic anemia disorder characterized by moderate to severe anemia without thrombocytopenia, variable degrees of neutropenia, and bone marrow biopsy findings of trilineage dysplasia and hypocellularity of erythroid and granulocytic lineages. Peripheral blood findings include anisocytosis, macrocytosis, poikilocytosis, elliptocytes, and fragmented erythrocytes.	Rare genetic hematologic disease
Orphanet:363722	Alexander disease type II	GFAP	1	An astrogliopathy and a form of Alexander disease (AxD) characterized by ataxia, bulbar symptoms, spastic paraparesis, palatal myoclonus, and autonomic symptoms.	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:363717	Alexander disease type I	GFAP	1	An astrogliopathy and the most severe and common form of Alexander disease (AxD), presenting before the age of 4 and characterized by seizures, megalencephaly and developmental delay with progressive deterioration.	Rare genetic neurological disorder
Orphanet:363710	Spinocerebellar ataxia type 37	DAB1;SCA37	2	Spinocerebellar ataxia type 37 (SCA37) is a subtype of autosomal dominant cerebellar ataxia type 1 (ADCA type 1; see this term), characterized by a cerebellar syndrome along with altered vertical eye movements.	Rare genetic neurological disorder
Orphanet:363700	Neurofibromatosis type 1 due to NF1 mutation or intragenic deletion	NF1	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic skin disease;Rare genetic renal disease;Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic tumor
Orphanet:363694	Hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome	SARS2	1	Hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome is a rare, genetic, mitochondrial disease characterized by early-onset progressive renal failure, manifesting with hyperuricemia, hyponatremia, hypomagnesemia, hypochloremic metabolic alkalosis, elevated BUN and polyuria, associated with systemic manifestations which include pulmonary hypertension, failure to thrive, global developmental delay, hypotonia and ventricular hypertrophy. Additional features include prematurity, elevated serum lactate, diabetes mellitus and, in some, pancytopenia.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:363686	Severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome	GATAD2B	1	Severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome is a rare, genetic, syndromic intellectual disability disorder characterized by global development delay with very limited or absent speech and language, severe intellectual disability, long slender fingers, ocular abnormalities (typically strabismus or hypermetropia), and facial dysmorphism that includes a grimacing facial expression, a tubular-shaped nose with a prominent, broad base and tip, and other variable features, such as broad forehead, hypertelorism, deep-set eyes, narrow palpebral fissures, short philtrum and/or broad mouth.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:363677	Childhood-onset autosomal recessive myopathy with external ophthalmoplegia	MYH2	1	 distal) muscles. Muscle biopsy shows type 1 fiber uniformity, absent, or abnormally small, type 2A fibers, increased variability of fiber size, internalized nuclei and/or fatty infiltration.	Rare genetic eye disease;Rare genetic neurological disorder
Orphanet:364195	NA	BLMH	1	NA	NA
Orphanet:363417	Temtamy preaxial brachydactyly syndrome	CHSY1	1	Temtamy preaxial brachydactyly syndrome is a rare, genetic dysostosis syndrome characterized by bilateral, symmetrical, preaxial brachydactyly associated with hyperphalangy, motor developmental delay and intellectual disability, growth retardation, sensorineural hearing loss, dental abnormalities (incuding misalignment of teeth, talon cusps, microdontia), and facial dysmorphism that includes plagiocephaly, round face, hypertelorism, malar hypoplasia, malformed ears, microstomia and micro/retrognathia.	Rare inborn errors of metabolism;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic neurological disorder;Genetic otorhinolaryngologic disease
Orphanet:363409	Fetal akinesia-cerebral and retinal hemorrhage syndrome	DNM2	1	Fetal akinesia-cerebral and retinal hemorrhage syndrome is a rare, lethal, congenital myopathy syndrome characterized by decreased fetal movements and polyhydraminos in utero and the presence of akinesia, severe hypotonia with respiratory insufficiency, absent reflexes, joint contractures, skeletal abnormalities with thin ribs and bones, intracranial and retinal hemorrhages and decreased birth weight in the neonate.	Rare genetic neurological disorder
Orphanet:363412	Hypomyelination with brain stem and spinal cord involvement and leg spasticity	DARS	1	Hypomyelination with brain stem and spinal cord involvement and leg spasticity is a rare, genetic, leukodystrophy disorder characterized by diffuse hypomyelination in the supratentorial brain white matter, brain stem and spinal cord. Patients usually present nystagmus, lower limb spasticity, hypotonia, and motor developmental delay, as well as MRI signal abnormalities involving the corpus callosum, anterior brainstem, pyramidal tracts, superior and inferior cerebellar peduncles, dorsal columns and/or lateral corticospinal tracts.	Rare genetic neurological disorder
Orphanet:363432	Autosomal recessive congenital cerebellar ataxia due to GRID2 deficiency	GRID2	1	A rare, genetic, slowly progressive neurodegenerative disease resulting from GRID2 deficiency characterized by motor, speech and cognitive delay, hypotonia, truncal and appendicular ataxia, and eye movement abnormalities (tonic upgaze, nystagmus, oculomotor apraxia). Intention tremor may also be associated. Brain imaging reveals progressive cerebellar atrophy with cerebellar flocculus particularly affected.	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:363424	Multiple mitochondrial dysfunctions syndrome type 3	IBA57	1	A rare neurometabolic disease, due to a lipoic acid biosynthesis defect, with a highly variable phenotype, typically characterized by early-onset acute or subacute developmental delay or regression frequently associated with feeding difficulties. Clinical severity is variable and may range from mild cases which present a later onset with slow neurological deterioration and general improvement over time to severe cases with clinical signs since birth and leading to early death. Associated manifestations include hypotonia, vision loss, respiratory failure, seizures, and intellectual disability. Brain magnetic resonance imaging frequently shows cavitating leukoencephalopathy with lesions in the periventricular/central white matter and parieto-occiîtal lobes.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:363396	High myopia-sensorineural deafness syndrome	SLITRK6	1	High myopia-sensorineural deafness syndrome is a rare genetic disease characterized by high myopia, typically ranging from -6.0 to -11.0 diopters, and moderate to profound, bilateral, progressive sensorineural hearing loss with prelingual-onset. Affected individuals do not present other systemic, ocular or connective tissue manifestations.	Genetic otorhinolaryngologic disease;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:363400	Severe neurodegenerative syndrome with lipodystrophy	BSCL2	1	Severe neurodegenerative syndrome with lipodystrophy is a rare, genetic, neurodegenerative disorder characterized by progressive psychomotor and cognitive regression (manifesting with gait ataxia, spasticity, loss of language, mild to severe intellectual disability, pyramidal and extrapyramidal signs and, frequently, development of tretraplegia or tetraparesis) associated with variable degrees of lipodystrophy, hepatomegaly, hypertriglyceridemia and muscular hypertorphy. Hyperactivity, tremor and development of seizures may also be associated.	Rare genetic neurological disorder;Rare genetic skin disease;Rare genetic endocrine disease
Orphanet:363618	LMNA-related cardiocutaneous progeria syndrome	LMNA	1	LMNA-related cardiocutaneous progeria syndrome is a rare, genetic, premature aging syndrome characterized by adulthood-onset cutaneous manifestations that result in a prematurely aged appearance (i.e. premature thinning and graying of scalp hair, loss of subcutaneous fat, tightening of skin) associated with prominent cardiovascular manifestations, such as accelerated atherosclerosis, calcific valve disease, and cardiomyopathy. Patients present loss of eyebrows and eyelashes in childhood and have a predisposition to develop malignancies.	Rare genetic skin disease;Laminopathy
Orphanet:363623	Autosomal recessive limb-girdle muscular dystrophy type 2T	GMPPB	1	A form of limb-girdle muscular dystrophy, that can present from birth to early childhood, characterized by hypotonia, microcephaly, mild proximal muscle weakness (leading to delayed walking and difficulty climbing stairs), mild intellectual disability and epilepsy. Additional manifestations reported in some patients include cataracts, nystagmus, cardiomyopathy, and respiratory insufficiency.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:363649	Mandibular hypoplasia-deafness-progeroid features-lipodystrophy syndrome	POLD1	1	Mandibular hypoplasia-deafness-progeroid syndrome is a rare, genetic, premature aging disease characterized by sensorineural deafness, generalized lack of subcutaneous fatty tissue (although with increased truncal deposition) noted from childhood, scleroderma, and facial dysmorphism which includes prominent eyes, a beaked nose, small mouth, crowded teeth and mandibular hypoplasia. Other associated features include growth delay, joint contractures, telangiectasia, hypogonadism (with lack of breast development in females), cryptorchidism, skeletal muscle atrophy, hypertriglycemia and diabetes mellitus/insulin resistance.	Genetic otorhinolaryngologic disease;Rare genetic skin disease;Rare genetic endocrine disease;Rare genetic developmental defect during embryogenesis
Orphanet:363654	X-linked parkinsonism-spasticity syndrome	ATP6AP2	1	A rare, genetic, neurological disorder characterized by parkinsonian features (including resting or action tremor, cogwheel rigidity, hypomimia and bradykinesia) associated with variably penetrant spasticity, hyperactive deep tendon reflexes and Babinski sign.	Rare genetic neurological disorder
Orphanet:363665	Acroosteolysis-keloid-like lesions-premature aging syndrome	PDGFRB	1	A rare, genetic, progeroid syndrome disorder characterized by a prematurely aged appearance (including lipoatrophy, thin, translucent skin, sparse, thin hair, and skeletal muscle atrophy), delayed tooth eruption, keloid-like lesions on pressure regions, and skeletal abnormalities including marked acroosteolysis, brachydactyly with small hands and feet, kyphoscoliosis, osteopenia, and progressive joint contractures in the fingers and toes. Craniofacial features include a thin calvarium, delayed closure of the anterior fontanel, flat occiput, shallow orbits, malar hypoplasia and narrow nose.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:363540	Leukoencephalopathy with mild cerebellar ataxia and white matter edema	CLCN2	1	NA	Rare genetic neurological disorder
Orphanet:363543	Autosomal recessive limb-girdle muscular dystrophy type 2R	DES	1	NA	Rare genetic neurological disorder
Orphanet:363549	Acute encephalopathy with biphasic seizures and late reduced diffusion	ADORA2A	1	A rare childhood-onset epilepsy syndrome associated with infection and characterized by a biphasic clinical course. The initial symptom is a prolonged febrile seizure on day 1 (the first phase). Afterwards, patients have variable levels of consciousness from normal to coma. Irrespective of the consciousness levels, magnetic resonance imaging (MRI) during the first 2 days shows no abnormality. During the second phase (usually days 4 - 6), patients show a cluster of seizures and deterioration of consciousness. Diffusion-weighted images (DWI) on MRI reveal the brain lesions with reduced diffusion predominantly in the subcortical white matter. After the second acute phase, consciousness levels improve with the emerging focal neurological signs. Neurological outcomes of AESD vary from normal to mild or severe sequelae including cerebral atrophy, mental retardation, paralysis and epilepsy.	Rare genetic neurological disorder
Orphanet:363611	Intellectual disability-feeding difficulties-developmental delay-microcephaly syndrome	CTCF	1	Intellectual disability-feeding difficulties-developmental delay-microcephaly syndrome is a rare, genetic, syndromic intellectual disability disorder characterized by borderline to severe intellectual disability, global development delay, feeding difficulties, microcephaly, short stature and mild facial dysmorphism, including thick eyebrows, long eyelashes, prominent incisors and/or thin upper lip. Other associated features may include hypermetropia with or without esotropia, behavioral anomallies (e.g. autistic behavior, sleeping disturbances), urogenital abnormalities (e.g. crytorchidism, inguinal hernia), single palmar crease, fifth-finger clinodactyly and cardiac defects (e.g. ASD, PDA).	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:363494	Non-seminomatous germ cell tumor of testis	KITLG;SPRY4	2	Testicular non seminomatous germ cell tumor describes a group of testicular germ cell tumors (see this term) occurring in the third decade of life (mean age: 25 years) with a usually painless unilateral mass in the scrotum or in some cases with gynaecomastia and/or back and flack pain and characterized by a more aggressive clinical course than testicular seminomatous germ cell tumors (see this term) with rapid involvement of blood vessels and a poorer prognosis. Histologically, they can be either undifferentiated (embryonal carcinoma), differentiated (teratoma, yolk sac tumor, choriocarcinoma), or can consist of a mixture of seminomatous and nonseminomatous components.	
Orphanet:363523	Hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome	COG6	1	Hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome is a rare, genetic, syndromic intellectual disability disorder characterized by severe intellectual disability with significant speech and language impairment, hypohydrosis (often resulting in hyperthermia) with normal sweat gland appearance, tooth enamel hypoplasia, palmoplantar hyperkeratosis and a high frequency of acquired microcephaly. Mild facial dysmorphism, including lateral flaring of the eyebrows, broad nasal tip, and thick vermilion border, may also be observed.	Rare genetic neurological disorder;Rare genetic skin disease
Orphanet:363534	Mitochondrial DNA depletion syndrome, hepatocerebrorenal form	TWNK	1	#64258;exia, ataxia, sensory neuropathy, epilepsy, sensorineural hearing impairment, psychomotor regression, athetosis, nystagmus, and/or ophthalmoplegia. Patients typically present with recurrent vomiting, severe failure to thrive, feeding difficulties, and fasting hypoglycemia.	Rare genetic renal disease;Rare genetic neurological disorder;Rare genetic hepatic disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic gastroenterological disease
Orphanet:363528	Intellectual disability-strabismus syndrome	ADAT3	1	Intellectual disability-strabismus syndrome is a rare, genetic, syndromic intellectual disability disorder characterized by moderate to severe intellectual disability and esotropia. Other associated features may include growth failure (underweight, failure to thrive, short stature), microcephaly, tone abnormalities (hypotonia, spasticity), epilepsy, behavioral problems (hyperactivity, aggressiveness), and/or abnormal brain morphology, including arachnoid cyst, cerebral atrophy, mild ventriculomegaly, abnormal CNS myelination or corpus callosum agenesis.	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:363444	THOC6-related developmental delay-microcephaly-facial dysmorphism syndrome	THOC6	1	THOC6-related developmental delay-microcephaly-facial dysmorphism syndrome is a rare, genetic, syndromic intellectual disability disorder characterized by global development delay, microcephaly, moderate to severe intellectual disability and facial dysmorphism which includes tall forehead, high anterior hairline, short upslanting palpebral fissures, deep-set eyes and a long nose with a low-hanging columella. Additionally, congenital renal and cardiac malformations (such as horseshoe kidney, unilateral renal agenesis atrioventricular septal defects, patent ductus arteriosus), as well as corpus callosum dysplasia, may be associated.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:363454	BICD2-related autosomal dominant childhood-onset proximal spinal muscular atrophy	BICD2	1	NA	Rare genetic neurological disorder
Orphanet:357191	NA	EGFR;KRAS;ALK;EML4	4	NA	NA
Orphanet:357194	NA	KRAS	1	NA	NA
Orphanet:357329	Combined immunodeficiency due to IL21R deficiency	IL21R	1	A rare, genetic, non-severe combined immunodeficiency disorder characterized by variable B- and T-cell defects (including defective B-cell differentiation and impaired T-cell proliferation to mitogens and bacterial antigens) and natural killer cell dysfunction (ranging from impaired cytotoxity to lymphopenia) due to IL21R deficiency, manifesting with recurrent respiratory and/or gastrointestinal tract infections and, in some cases, with severe, chronic, progressive cholangitis and liver cirrhosis associated with cryptosporidial infection.	Rare genetic immune disease
Orphanet:357237	Severe combined immunodeficiency due to CARD11 deficiency	CARD11	1	Severe combined immunodeficiency due to CARD11 deficiency is a rare combined T and B cell immunodeficiency characterized by normal numbers of T and B lymphocytes, increased numbers of transitional B cells and hypo- to agammaglobulinemia, decreased numbers of regulatory T cells and defects in T-cell functions. It presents with severe susceptibility to infections, including opportunistic infections.	Rare genetic immune disease
Orphanet:356978	D,L-2-hydroxyglutaric aciduria	SLC25A1	1	A rare inborn error of metabolism characterized by severe neonatal epileptic encephalopathy, episodes of apnea and respiratory distress, severe global developmental delay or absent psychomotor development, severe muscular hypotonia or absent voluntary movements, feeding difficulties and failure to thrive, absence of visual contact, abnormal brain morphology (including cerebral atrophy, ventriculomegaly and hypoplasia or dysplasia of the corpus callosum), mild dysmorphic features (frontal bossing, hypertelorism, downslanting palpebral fissures, flat nasal bridge), elevated CSF and plasma lactate and urinary Krebs cycle metabolites.	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:356961	SLC35A2-CDG	SLC35A2	1	A rare, congenital disorder of glycosylation characterized by severe or profound global developmental delay, early epileptic encephalopathy, muscular hypotonia, dysmorphic features (coarse facies, thick eyebrows, broad nasal bridge, thick lips, inverted nipples), variable ocular defects and brain morphological abnormalities on brain MRI (cerebral atrophy, thin corpus callosum).	Rare inborn errors of metabolism;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:357008	Hemolytic uremic syndrome with DGKE deficiency	DGKE	1	NA	Rare genetic hematologic disease;Rare genetic renal disease
Orphanet:356996	ANK3-related intellectual disability-sleep disturbance syndrome	ANK3	1	 gene). Additional features observed may incude muscular hypotonia and spasticity. Epilepsy, chronic hunger, and dysmorphic facial features have been reported.	Rare genetic neurological disorder
Orphanet:357043	Amyotrophic lateral sclerosis type 4	SETX	1	A rare, genetic motor neuron disease characterized by late childhood- or adolescent-onset of slowly progressive, severe, distal limb muscle weakness and wasting, in association with pyramidal signs, normal sensation, and absence of bulbar involvement, leading to degeneration of motor neurons in the brain and spinal cord.	Rare genetic neurological disorder
Orphanet:357034	Non-hereditary retinoblastoma	RB1;MYCN	2	NA	
Orphanet:357027	Hereditary retinoblastoma	RB1;MYCN	2	NA	Rare genetic eye disease;Rare genetic tumor
Orphanet:357074	Autosomal recessive cutis laxa type 2, classic type	ATP6V1E1;ATP6V1A;ATP6V0A2	3	NA	Rare inborn errors of metabolism;Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic neurological disorder
Orphanet:357064	Autosomal recessive cutis laxa type 2B	PYCR1	1	A rare, hereditary, developmental defect with connective tissue involvement characterized by cutis laxa of variable severity, in utero growth restriction, congenital hip dislocation and joint hyperlaxity, wrinkling of the skin, in particular the dorsum of hands and feet, and progeroid facial features. Hypotonia, developmental delay, and intellectual disability are common. In addition, cataracts, corneal clouding, wormian bones, lipodystrophy and osteopenia have been reported.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare inborn errors of metabolism;Rare genetic skin disease
Orphanet:352654	Early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome	UCHL1	1	A rare, genetic, neurodegenerative disease characterized by normal early development followed by childhood onset optic atrophy with progressive vision loss and eventually blindness, followed by progressive neurological decline that typically includes cerebellar ataxia, nystagmus, dorsal column dysfunction (decreased vibration and position sense), spastic paraplegia and finally tetraparesis.	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:352662	Corneal intraepithelial dyskeratosis-palmoplantar hyperkeratosis-laryngeal dyskeratosis syndrome	NLRP1	1	Corneal intraepithelial dyskeratosis-palmoplantar hyperkeratosis-laryngeal dyskeratosis syndrome is a rare, genetic, corneal dystrophy disorder characterized by corneal opacification and dyskeratosis (which may cause visual impairment), associated with systemic features including palmoplantar hyperkeratosis, laryngeal dyskeratosis, pruritic hyperkeratotic scars, chronic rhintis, dyshidrosis and/or nail thickening.	Rare genetic skin disease;Rare genetic eye disease
Orphanet:352641	Autosomal recessive cerebellar ataxia with late-onset spasticity	GBA2	1	A rare, genetic neurodegenerative disease characterized by childhood or adolescent-onset of cerebellar ataxia with dysarthria which slowly progresses and associates pyramidal signs, including lower limb spasticity, brisk reflexes, and Babinski and Hoffman signs. Patients typically present cerebellar ataxia with development of increasing asymmetric spasticity in upper and lower limbs, and variable axonal sensory or sensorimotor neuropathy. Additional heterogeneous features, including pes cavus, scoliolis, and abnormalities of the brain (e.g. cerebral atrophy), may also be associated.	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:352649	Brain dopamine-serotonin vesicular transport disease	SLC18A2	1	A rare infantile-onset neurometabolic disease characterized by dystonia, parkinsonism, nonambulation, autonomic dysfunction, developmental delay and mood disturbances.	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:352596	Progressive myoclonic epilepsy with dystonia	TBC1D24	1	Progressive myoclonic epilepsy with dystonia is a rare, genetic epilepsy syndrome characterized by neonatal or early infantile onset of severe, progressive, typically frequent and prolonged myoclonic seizures that are refractory to treatment, associated with localized and/or generalized paroxysmal dystonia (which later becomes persistent). Other features include severe hypotonia, hemiplegia, psychomotor regression (or lack of psychomotor development) and progressive cerebral and cerebellar atrophy, with affected individuals becoming progressively non-reactive to environmental stimuli.	Rare genetic neurological disorder
Orphanet:352577	Severe feeding difficulties-failure to thrive-microcephaly due to ASXL3 deficiency syndrome	ASXL3	1	Severe feeding difficulties-failure to thrive-microcephaly due to ASXL3 deficiency syndrome is rare, genetic, syndromic intellectual disability disorder with a variable phenotypic presentation typically characterized by microcephaly, severe feeding difficulties, failure to thrive, severe global development delay that frequently results in absent/poor speech, moderate to profound intellectual disability, hypotonia and a distinctive facies that includes prominent forehead, high-arched, thin eyebrows, hypertelorism, downslanting palpebral fissures, long, tubular nose with broad tip and prominent nasal bridge and wide mouth with full, everted lower lip.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:352587	Focal epilepsy-intellectual disability-cerebro-cerebellar malformation	TBC1D24	1	Focal epilepsy-intellectual disability-cerebro-cerebellar malformation is a rare, genetic neurological disorder characterized by early infantile-onset of seizures, borderline to moderate intellectual disability, cerebellar features including dysarthria and ataxia and cerebellar atrophy and cortical thickening observed on MRI imaging. Seizures are typically focal (with prominent eye blinking, facial and limb jerking), precipitated by fever and often commence with an oral sensory aura (anesthetized tongue sensation). When not properly controlled by anti-epileptic medication, weekly frequency and persistance into adult life is observed.	Rare genetic neurological disorder
Orphanet:352582	Familial infantile myoclonic epilepsy	CPLX1;TBC1D24	2	A rare, genetic, infantile epilepsy syndrome disease characterized by neonatal- to infancy-onset myoclonic focal seizures occurring in various members of a family, associated in some with mild dysarthria, ataxia and borderline-to-moderate intellectual disability.	Rare genetic neurological disorder
Orphanet:352734	Minimal pigment oculocutaneous albinism type 1	TYR	1	An extremely rare form of OCA1 with minimal pigment present, characterized by blond hair, variable iris transillumination, visual acuity ranging from 20/80-20/200 and white skin, with or without skin nevi.	Rare inborn errors of metabolism;Rare genetic eye disease;Rare genetic skin disease
Orphanet:352737	Temperature-sensitive oculocutaneous albinism type 1	TYR	1	An extremely rare form of OCA1 characterized by the production of temperature sensitive tyrosinase proteins leading to dark hair on the legs, arms and chest (cooler body areas) and white hair on the scalp, axilla and pubic area (warmer body areas).	Rare inborn errors of metabolism;Rare genetic eye disease;Rare genetic skin disease
Orphanet:352709	CLN13 disease	CTSF	1	NA	Rare genetic eye disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:352712	Facial dysmorphism-immunodeficiency-livedo-short stature syndrome	POLE	1	Facial dysmorphism-immunodeficiency-livedo-short stature syndrome is a rare genetic disease characterized by facial dysmorphism with malar hypoplasia and high forehead, immunodeficiency resulting in recurrent infections, impaired growth (with normal growth hormone production and response) resulting in short stature, and livedo affecting face and extremities. Immunological analyses show low memory B-cell and naïve T cell counts, decreased T cell proliferation, and reduced IgM, IgG2 and IgG4 titers. Patients do not exhibit increased susceptibility to cancer.	Rare genetic developmental defect during embryogenesis;Rare genetic immune disease
Orphanet:352718	Progressive retinal dystrophy due to retinol transport defect	RBP4	1	Progressive retinal dystrophy due to retinol transport defect is a rare, genetic, metabolite absorption and transport disorder characterized by progressive rod-cone dystrophy, usually presenting with impaired night vision in childhood, progressive loss of visual acuity and severe retinol deficiency without keratomalacia. Association with ocular colobomas, severe acne and hypercholesterolemia has been reported.	Rare genetic eye disease;Rare inborn errors of metabolism
Orphanet:352723	Attenuated Chédiak-Higashi syndrome	LYST	1	A very rare and atypical form of Chédiak-Higashi syndrome (CHS), a genetic disorder characterized by partial oculocutaneous albinism, severe immunodeficiency, mild bleeding, neurological dysfunction and lymphoproliferative disorder.	Rare genetic neurological disorder
Orphanet:352665	Neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-skeletal anomalies syndrome due to 9q21.3 microdeletion	HNRNPK	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic cardiac disease;Rare genetic bone disease;Rare chromosomal anomaly
Orphanet:352670	Autosomal dominant intermediate Charcot-Marie-Tooth disease type F	GNB4	1	A rare hereditary motor and sensory neuropathy disorder characterized by the typical CMT phenotype (slowly progressive distal muscle atrophy and weakness in upper and lower limbs, distal sensory loss in extremities, reduced or absent deep tendon reflexes and foot deformities) with nerve biopsy demonstrating demyelinating and axonal changes and nerve conduction velocities varying from the demyelinating to axonal range.	Rare genetic neurological disorder
Orphanet:352675	X-linked Charcot-Marie-Tooth disease type 6	PDK3	1	X-linked Charcot-Marie-Tooth disease type 6 is a rare, genetic, principally axonal, peripheral sensorimotor neuropathy characterized by an X-linked dominant inheritance pattern and the childhood-onset of slowly progressive, moderate to severe, distal muscle weakness and atrophy of the lower extremities, as well as distal, panmodal sensory abnormalities, bilateral foot deformities (pes cavus, clawed toes), absent ankle reflexes and gait abnormalities (steppage gait). Females are usually asymptomatic or only present mild manifestations (mild postural hand tremor, mild wasting of hand intrinsic muscles).	Rare genetic neurological disorder;Genetic otorhinolaryngologic disease
Orphanet:352682	Cobblestone lissencephaly without muscular or ocular involvement	LAMB1	1	A rare, genetic, cobblestone lissencephaly disease characterized by the presence of a constellation of brain malformations, including cortical gyral and sulcus anomalies, white matter signal abnormalities, cerebellar dysplasia and brainstem hypoplasia, existing alone or in conjunction with minimal muscular and ocular abnormalities, typically manifesting with severe developmental delay, increased head circumference, hydrocephalus and seizures.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:353277	Rubinstein-Taybi syndrome due to CREBBP mutations	CREBBP	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic renal disease;Inherited cancer-predisposing syndrome;Rare genetic endocrine disease;Rare genetic eye disease;Rare genetic bone disease
Orphanet:353220	Familial primary localized cutaneous amyloidosis	OSMR;IL31RA	2	NA	Rare genetic skin disease
Orphanet:353217	Epileptic encephalopathy with global cerebral demyelination	SLC25A12	1	Epileptic encephalopathy with global cerebral demyelination is a rare mitochondrial substrate carrier disorder characterized by severe muscular hypotonia, seizures (with or without episodic apnea) beginning in the first year of life, and arrested psychomotor development (affecting mainly motor skills). Severe spasticity with hyperreflexia has also been reported. Global cerebral hypomyelination is a characteristic imaging feature of this disease.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:352745	Oculocutaneous albinism type 7	LRMDA	1	Oculocutaneous albinism type 7 (OCA7), formerly called OCA5, is a form of oculocutaneous albinism (OCA; see this term) characterized by skin and hair hypopigmentation, nystagmus and iris transillumination.	Rare inborn errors of metabolism;Rare genetic eye disease;Rare genetic skin disease
Orphanet:352740	Ocular albinism with congenital sensorineural deafness	TYR;MITF	2	Ocular albinism with congenital sensorineural deafness is a rare, genetic, oculocutaneous disorder characterized by profound, congenital, sensorineural hearing loss in association with moderate to severe hypopigmentation of the ocular fundus, blue irides or partial heterochromia, and patchy or generalized hypopigmentation of the skin. White forelock, premature graying of hair, freckles, lentigines and café-au-lait macules are frequently associated. Other highly variable features include reduced visual acuity, strabismus, and an iris transillumination defect.	Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:353320	Pyruvate carboxylase deficiency, benign type	PC	1	Benign pyruvate carboxylase (PC) deficiency (Type C) is a rare, very mild form of PC deficiency characterized by episodic metabolic acidosis and normal or mildly delayed neurological development.	Rare inborn errors of metabolism
Orphanet:353327	Congenital myasthenic syndromes with glycosylation defect	ALG2;DPAGT1;GFPT1;ALG14;GMPPB	5	NA	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:353308	Pyruvate carboxylase deficiency, infantile type	PC	1	Infantile pyruvate carboxylase (PC) deficiency (Type A) is a rare, severe form of PC deficiency characterized by infantile-onset, mild to moderate lactic acidemia, and a generally severe course.	Rare inborn errors of metabolism
Orphanet:353314	Pyruvate carboxylase deficiency, severe neonatal type	PC	1	Severe neonatal pyruvate carboxylase (PC) deficiency (Type B) is a rare, extremely severe form of PC deficiency characterized by severe, early-onset metabolic acidosis, and a generally fatal outcome in early infancy.	Rare inborn errors of metabolism
Orphanet:353298	Roifman syndrome	RNU4ATAC	1	Roifman syndrome is a rare, genetic immuno-osseous dysplasia disorder characterized by pre- and post-natal growth retardation, hypotonia, borderline to moderate intellectual disability, retinal dystrophy, spondyloepiphyseal dysplasia (epiphyseal dysplasia, epiphyses ossification delay, vertebral changes) and skeletal anomalies (brachydactyly, fifth finger clinodactyly), as well as humeral immunodeficiency characterized by inability to generate specific antibodies and low circulating B-cells. Craniofacial dysmorphism, that typically inlcudes microcephaly, hypertelorism, long palpebral fissures, prominent eyelashes, a narrow, tubular, upturned nose with hypoplastic alae nasi, long philtrum and thin upper lip, are also associated.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare genetic immune disease;Rare genetic bone disease
Orphanet:353281	Rubinstein-Taybi syndrome due to 16p13.3 microdeletion	CREBBP	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic renal disease;Inherited cancer-predisposing syndrome;Rare genetic endocrine disease;Rare genetic eye disease;Rare chromosomal anomaly;Rare genetic bone disease
Orphanet:353284	Rubinstein-Taybi syndrome due to EP300 haploinsufficiency	EP300	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic renal disease;Inherited cancer-predisposing syndrome;Rare genetic endocrine disease;Rare genetic eye disease;Rare genetic bone disease
Orphanet:352403	Spectrin-associated autosomal recessive cerebellar ataxia	SPTBN2	1	 mutations, characterized by global development delay in infancy, followed by childhood-onset gait ataxia with limb dysmetria and dysdiadochokinesia, mild to severe intellectual disability, development of cerebellar atrophy, and abnormal eye movements (including a convergent squint, hypometric saccades, jerky pursuit movements and incomplete range of movement).	Rare genetic neurological disorder
Orphanet:352333	Congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome	ELOVL4	1	NA	Rare genetic neurological disorder;Rare genetic skin disease;Rare inborn errors of metabolism
Orphanet:352328	MEGDEL syndrome	SERAC1	1	MEGDEL syndrome is a rare, genetic, neurometabolic disorder characterized by neonatal hypoglycemia, features of sepsis that are not linked to infection, development of feeding problems, failure to thrive, transient liver dysfunction, and truncal hypotonia followed by dystonia and spasticity which results in psychomotor development arrest and/or regression. Progressive sensorineural deafness, intellectual disability and absent speech are also associated. Laboratory tests demonstrate 3-methylglutaconic aciduria and temporary elevated serum lactate and transaminases.	Genetic otorhinolaryngologic disease;Rare inborn errors of metabolism;Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:352447	Progressive external ophthalmoplegia-myopathy-emaciation syndrome	MGME1	1	Progressive external ophthalmoplegia-myopathy-emaciation syndrome is a rare mitochondrial oxidative phosphorylation disorder due to nuclear DNA anomalies characterized by progressive external ophthalmoplegia without diplopia, cerebellar atrophy, proximal skeletal muscle weakness with generalized muscle wasting, profound emaciation, respiratory failure, spinal deformity and facial muscle weakness (manifesting with ptosis, dysphonia, dysphagia and nasal speech). Intellectual disability, gastrointestinal symptoms (e.g. nausea, abdominal fullness, and loss of appetite), dilated cardiomyopathy and renal colic have also been reported.	Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:352530	Intellectual disability-obesity-brain malformations-facial dysmorphism syndrome	TRAPPC9	1	Intellectual disability-obesity-brain malformations-facial dysmorphism syndrome is a rare, syndromic intellectual disability primarily characterized by moderate to severe intellectual disability, true-to-relative microcephaly and brain abnormalities including a thin corpus callosum, cerebellar hypoplasia, cerebral white matter hypoplasia and multi-focal hyperintensity of cerebral white matter on MRI. Obesity and distinctive craniofacial dysmorphism (including brachycephaly, round face, straight eyebrows, synophrys, hypertelorism, epicanthus, wide and depressed nasal bridge, protruding ears with uplifted lobe, downslanting corners of the mouth) are additional features.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease
Orphanet:352563	Infantile hypertrophic cardiomyopathy due to MRPL44 deficiency	MRPL44	1	A rare mitochondrial oxidative phosphorylation disorder with complex I and IV deficiency characterized by hypertrophic cardiomyopathy, hepatic steatosis with elevated liver transaminases, exercise intolerance and muscle weakness. Neuro-opthalmological features (hemiplegic migraine, Leigh-like lesions on brain MRI, pigmentary retinopathy) have been reported later in life.	Rare genetic cardiac disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:352479	Autosomal recessive limb-girdle muscular dystrophy type 2U	ISPD	1	A rare subtype of autosomal recessive limb-girdle muscular dystrophy disorder characterized by infantile to childhood-onset of slowly progressive, principally proximal, shoulder and/or pelvic-girdle muscular weakness that typically presents with positive Gowers' sign and is associated with elevated creatine kinase levels, hyporeflexia, joint and achilles tendon contractures, and muscle hypertrophy, usually of the thighs, calves and/or tongue. Other highly variable features include cerebellar, cardiac and ocular abnormalities.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:352470	DNA2-related mitochondrial DNA deletion syndrome	DNA2	1	A rare, genetic, mitochondrial oxidative phosphorylation disorder characterized by either late-onset myopathy with progressive external ophthalmoplegia and muscular weakness (predominantly limb-girdle) or early-onset myopathy presenting with decreased fetal movements, congenital ptosis, progressive external ophthalmoplegia, hypotonia and, variably, joint contractures. Reduced content and multiple deletions of mitochondrial DNA is observed in muscle biopsy.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:352487	Digital anomalies-intellectual disability-short stature syndrome	EBP	1	NA	NA
Orphanet:352490	Autism spectrum disorder due to AUTS2 deficiency	AUTS2	1	A rare genetic syndromic intellectual disability characterized by global developmental delay and borderline to severe intellectual disability, autism spectrum disorder with obsessive behavior, stereotypies, hyperactivity but frequently friendly and affable personality, feeding difficulties, short stature, muscular hypotonia, microcephaly, characteristic dysmorphic features (hypertelorism, high arched eyebrows, ptosis, deep and/or broad nasal bridge, broad/prominent nasal tip, short and/or upturned philtrum, narrow mouth, and micrognathia), and skeletal anomalies (kyphosis and/or scoliosis, arthrogryposis, slender habitus and extremities). Other clinical features may include hernias, congenital heart defects, cryptorchidism and seizures.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:294415	Renal-hepatic-pancreatic dysplasia	NPHP3;NEK8	2	Renal-hepatic-pancreatic dysplasia is a rare, genetic, developmental defect during embryogenesis syndrome characterized by the triad of pancreatic fibrosis (and cysts, with a reduction of parenchymal tissue), renal dysplasia (with peripheral cortical cysts, primitive collecting ducts, glomerular cysts and metaplastic cartilage) and hepatic dysgenesis (enlarged portal areas containing numerous elongated binary profiles with a tendancy to perilobular fibrosis). Situs abnormalities, skeletal anomalies and anencephaly have also been associated. Patients that survive the neonatal period present renal insufficiency, chronic jaundice and insulin-dependent diabetes.	Ciliopathy;Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Rare genetic hepatic disease
Orphanet:294049	Reunion Island Larsen-like syndrome	B4GALT7	1	A rare, genetic, congenital disorder of glycosylation characterized by severe, pre- and post-natal short stature, joint hyperlaxity with multiple dislocations (elbows, fingers, hips, knees), and facial dysmorphism (round flat face, high forehead, hypertelorism, prominent bulging eyes with under-eye shadows, hypoplastic midface, microstomia, protruding lips). Other associated features may include cutaneous hyperextensibility, learning difficulties, and ocular abnormalities. Advanced carpal ossification, widened metaphyses, and, occasionally, radioulnar synostosis, scoliosis and a Swedish key appearance of the proximal femora, is observed on imaging.	Rare inborn errors of metabolism;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:294016	Microcephaly-capillary malformation syndrome	STAMBP	1	Microcephaly-capillary malformation syndrome is a rare, genetic vascular anomaly characterized by severe congenital microcephaly, poor somatic growth, diffuse multiple capillary malformations on the skin, intractable epilepsy, profound global developmental delay, spastic quadriparesis and hypoplastic distal phalanges.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:294023	Neonatal inflammatory skin and bowel disease	EGFR;ADAM17	2	Neonatal inflammatory skin and bowel disease is a rare, life-threatening, autoinflammatory syndrome with immune deficiency disorder characterized by early-onset, life-long inflammation, affecting the skin and bowel, associated with recurrent infections. Patients present perioral and perianal psoriasiform erythema and papular eruption with pustules, failure to thrive associated with chronic malabsorptive diarrhea, intercurrent gastrointestinal infections and feeding troubles, as well as absent, short or broken hair and trichomegaly. Recurrent cutaneous and pulmonary infections lead to recurrent blepharitis, otitis externa and bronchiolitis.	Rare genetic immune disease;Rare genetic skin disease;Rare genetic gastroenterological disease
Orphanet:293964	Hypoinsulinemic hypoglycemia and body hemihypertrophy	AKT2	1	Hypoinsulinemic hypoglycemia and body hemihypertrophy is a rare, genetic, endocrine disease characterized by neonatal macrosomia, asymmetrical overgrowth (typically manifesting as left-sided hemihypertrophy) and recurrent, severe hypoinsulinemic (or hypoketotic hypo-fatty-acidemic) hypoglycemia in infancy, which results in episodes of reduced consciousness and seizures.	Rare genetic developmental defect during embryogenesis
Orphanet:293978	Deficiency in anterior pituitary function-variable immunodeficiency syndrome	NFKB2	1	Deficiency in anterior pituitary function-variable immunodeficiency syndrome is a rare, genetic endocrine disease characterized by the association of common variable immunodeficiency, manifesting with hypogammaglobulinemia and recurrent or severe childhood-onset sinopulmonary infections, followed, possibly many years later, by symptomatic adrenocorticotropic hormone (ACTH) deficiency resulting from anterior pituitary hormone deficiency.	Rare genetic immune disease;Rare genetic endocrine disease
Orphanet:293955	Childhood encephalopathy due to thiamine pyrophosphokinase deficiency	TPK1	1	Childhood encephalopathy due to thiamine pyrophosphokinase deficiency is a rare inborn error of metabolism disorder characterized by early-onset, acute, encephalopathic episodes (frequently triggered by viral infections), associated with lactic acidosis and alpha-ketoglutaric aciduria, which typically manifest with variable degrees of ataxia, generalized developmental regression (which deteriorates with each episode) and dystonia. Other manifestations include spasticity, seizures, truncal hypotonia, limb hypertonia, brisk tendon reflexes and reversible coma.	Rare inborn errors of metabolism
Orphanet:293948	1p21.3 microdeletion syndrome	DPYD	1	1p21.3 microdeletion syndrome is an extremely rare chromosomal anomaly characterized by severe speech and language delay, intellectual deficiency, autism spectrum disorder(see this term).	Rare genetic neurological disorder;Rare chromosomal anomaly
Orphanet:293936	EDICT syndrome	MIR184	1	EDICT (endothelial dystrophy-iris hypoplasia-congenital cataract-stromal thinning) syndrome is a very rare eye disorder representing a constellation of autosomal dominantly inherited ocular findings, including early-onset or congenital cataracts, corneal stromal thinning, early-onset keratoconus, corneal endothelial dystrophy, and iris hypoplasia.	Rare genetic eye disease
Orphanet:293925	Lethal occipital encephalocele-skeletal dysplasia syndrome	CYP26B1	1	Lethal occipital encephalocele-skeletal dysplasia syndrome is a rare, genetic, bone development disorder characterized by occipital and parietal bone hypoplasia leading to occipital encephalocele, calvarial mineralization defects, craniosynostosis, radiohumeral fusions, oligodactyly and other skeletal anomalies (arachnodactyly, terminal phalangeal aplasia of the thumbs, bilateral absence of the great toes, pronounced bilateral angulation of femora, shortened limbs, advanced osseous maturation). Fetal death in utero is associated.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:293910	Familial isolated arrhythmogenic ventricular dysplasia, right dominant form	TTN;PKP2;RYR2;TGFB3;DSC2;DSG2;DSP;JUP;LDB3;LMNA;TMEM43;CTNNA3	12	NA	Rare genetic cardiac disease;Laminopathy
Orphanet:293899	Familial isolated arrhythmogenic ventricular dysplasia, biventricular form	TTN;TMEM43;CTNNA3;PKP2;RYR2;TGFB3;DSC2;DSG2;DSP;JUP;LDB3;LMNA	12	NA	Rare genetic cardiac disease;Laminopathy
Orphanet:293888	Familial isolated arrhythmogenic ventricular dysplasia, left dominant form	TTN;PKP2;RYR2;TGFB3;DSC2;DSG2;DSP;JUP;LDB3;LMNA;TMEM43;CTNNA3	12	NA	Rare genetic cardiac disease;Laminopathy
Orphanet:293864	Hypoplastic pancreas-intestinal atresia-hypoplastic gallbladder syndrome	RFX6	1	Hypoplastic pancreas-intestinal atresia-hypoplastic gallbladder syndrome is a rare, potentially fatal, genetic, visceral malformation syndrome characterized by neonatal diabetes, hypoplastic or annular pancreas, duodenal and jejunal atresia, as well as gallbladder aplasia or hypoplasia. Patients typically present intrauterine growth restriction, failure to thrive, malnutrition, intestinal malrotation, malabsorption, conjugated hyperbilirubinemia, acholia and infections. Cardiac anomalies may also be associated.	Rare genetic developmental defect during embryogenesis
Orphanet:293843	3MC syndrome	COLEC10;MASP1;COLEC11	3	3MC syndrome describes a rare developmental disorder, that unifies the overlapping autosomal recessive disorders previously known as Carnevale, Mingarelli, Malpuech and Michels syndromes, characterized by a spectrum of developmental anomalies that include distinctive facial dysmorphism (i.e. hypertelorism, blepharophimosis, blepharoptosis, highly arched eyebrows), cleft lip and/or palate, craniosynostosis, learning disability, radioulnar synostosis and genital and vesicorenal anomalies. Less common features reported include anterior chamber defects, cardiac anomalies (e.g. ventricular septal defect; see this term), caudal appendage, umbilical hernia/omphalocele and diastasis recti.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:293822	MITF-related melanoma and renal cell carcinoma predisposition syndrome	MITF	1	MITF-related melanoma and renal cell carcinoma predisposition syndrome is an inherited cancer-predisposing syndrome due to a gain-of-function germline mutation in the MITF gene, associated with a higher incidence of amelanotic and nodular melanoma, multiple primary melanomas and increase in nevus number and size. It may also predispose to co-occurring melanoma and renal cell carcinoma and to pancreatic cancer.	
Orphanet:293825	Congenital dyserythropoietic anemia type IV	KLF1	1	Congenital dyserythropoietic anemia type IV (CDA IV) is a newly discovered form of CDA (see this term) characterized by ineffective erythropoiesis and hemolysis that leads to severe anemia at birth.	Rare genetic hematologic disease
Orphanet:293707	Blepharophimosis-intellectual disability syndrome, MKB type	MED12	1	A rare, X-linked, syndromic, intellectual disability disorder affecting only boys and characterized by global development delay with little or no speech, urogenital abnormalities, including scrotal hypoplasia, micro penis, and cryptorchidism, autistic behavior, and facial dysmorphism. Most typical facial features are ptosis, blepharophimosis, a bulbous nasal tip, a long philtrum, and maxillar hypoplasia with full cheeks. Other variable features include microcephaly, hearing loss, dental anomalies, and hyperextensible joints.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:293633	PYCR1-related De Barsy syndrome	PYCR1	1	NA	Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic eye disease;Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:289891	Hypermethioninemia due to glycine N-methyltransferase deficiency	GNMT	1	Hypermethioninemia due to glycine N-methyltransferase deficiency is a rare, genetic inborn error of metabolism characterized by a relatively benign clinical phenotype, with only mild to moderate hepatomegaly reported, in addition to laboratory studies revealing permanent, greatly increased hypermethioninemia, mild to moderate elevation of aminotransferases and highly elevated plasma S-adenosyl-methionine with normal S-adenosylhomocysteine and total homocysteine.	Rare inborn errors of metabolism
Orphanet:289863	Atypical glycine encephalopathy	SLC6A9;AMT;GCSH;GLDC	4	A rare form of glycine encephalopathy presenting disease onset or clinical manifestations that differ from neonatal or infantile glycine encephalopathy.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:289916	Vitamin B12-unresponsive methylmalonic acidemia type mut0	MUT	1	Vitamin B12-unresponsive methylmalonic acidemia type mut0 is an inborn error of metabolism characterized by recurrent ketoacidotic comas or transient vomiting, dehydration, hypotonia and intellectual deficit, which does not respond to administration of vitamin B12.	Rare inborn errors of metabolism;Rare genetic renal disease
Orphanet:289857	Neonatal glycine encephalopathy	AMT;GCSH;GLDC	3	Neonatal glycine encephalopathy is a frequent, usually severe form of glycine encephalopathy (GE; see this term) characterized by coma, apnea, hypotonia, seizure and myoclonic jerks in the neonatal period, and subsequent developmental delay.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:289860	Infantile glycine encephalopathy	SLC6A9;AMT;GCSH;GLDC	4	Infantile glycine encephalopathy is a mild to severe form of glycine encephalopathy (GE; see this term), characterized by early hypotonia, developmental delay and seizures.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:289846	Glutathione synthetase deficiency with 5-oxoprolinuria	GSS	1	NA	Rare inborn errors of metabolism;Rare genetic hematologic disease
Orphanet:289849	Glutathione synthetase deficiency without 5-oxoprolinuria	GSS	1	NA	Rare inborn errors of metabolism;Rare genetic hematologic disease
Orphanet:289560	Mitochondrial membrane protein-associated neurodegeneration	C19ORF12	1	A rare neurodegenerative disorder characterized by iron accumulation in specific regions of the brain, usually the basal ganglia, and associated with slowly progressive pyramidal (spasticity) and extrapyramidal (dystonia) signs, motor axonal neuropathy, optic atrophy, cognitive decline, and neuropsychiatric abnormalities.	Rare genetic eye disease;Rare genetic neurological disorder
Orphanet:289548	Inherited isolated adrenal insufficiency due to partial CYP11A1 deficiency	CYP11A1	1	Inherited isolated adrenal insufficiency due to partial CYP11A1 deficiency is a rare, genetic, chronic, primary adrenal insufficiency disorder, due to partial loss-of-function CYP11A1 mutations, characterized by early-onset adrenal insufficiency without associated abnormal external male genitalia. Patients present with signs of adrenal crisis, including electrolite abnormalities, severe weakness, recurrent vomiting and seizures. Ultrasound reveals absent (or very small) adrenal glands.	Rare genetic endocrine disease
Orphanet:289539	BAP1-related tumor predisposition syndrome	BAP1	1	BAP1-related tumor predisposition syndrome (TPDS) is an inherited cancer-predisposing syndrome, associated with germline mutations in BAP1 tumor suppressor gene. The most commonly observed cancer types include uveal melanoma, malignant mesothelioma, renal cell carcinoma, lung, ovarian, pancreatic, breast cancer and meningioma, with variable age of onset. Common cutaneous manifestations include malignant melanoma, basal cell carcinoma and benign melanocytic BAP1-mutated atypical intradermal tumors (MBAIT) presenting as multiple skin-coloured to reddish-brown dome-shaped to pedunculated, well-circumscribed papules with an average size of 5 mm, histologically predominantly composed of epithelioid melanocytes with abundant amphophilic cytoplasm, prominent nucleoli and large, vesicular nuclei that vary substantially in size and shape.	
Orphanet:289601	Hereditary arterial and articular multiple calcification syndrome	NT5E	1	Hereditary arterial and articular multiple calcification syndrome is a very rare genetic vascular disease of autosomal recessive inheritance, described in less than 20 patients to date, characterized by adult-onset (as early as the second decade of life) isolated calcification of the arteries of the lower extremities (including the iliac, femoral, and tibial arteries) as well as the capsule joints of the fingers, wrists, ankles and feet, and that usually manifests with mild paresthesias of the lower extremities, intense joint pain and swelling, and early onset arthritis of affected joints.	
Orphanet:289586	Exfoliative ichthyosis	SERPINB8;CSTA	2	Exfoliative ichthyosis is an inherited, non-syndromic, congenital ichthyosis disorder characterized by the infancy-onset of palmoplantar peeling of the skin (aggravated by exposure to water and by occlusion) associated with dry, scaly skin over most of the body. Pruritus and hypohidrosis may also be associated. Well-demarcated areas of denuded skin appear in moist and traumatized regions and skin biopsies reveal reduced cell-cell adhesion in the basal and suprabasal layers, prominent intercellular edema, numerous aggregates of keratin filaments in basal keratinocytes, attenuated cornified cell envelopes, and epidermal barrier impairment.	Rare genetic skin disease;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Serpinopathy
Orphanet:293381	Epithelial recurrent erosion dystrophy	COL17A1	1	Epithelial recurrent erosion dystrophy (ERED) is a rare form of superficial corneal dystrophy (see this term) characterized by recurrent episodes of epithelial erosions from childhood in the absence of associated diseases, with occasional impairment of vision.	Rare genetic eye disease
Orphanet:293603	Congenital hereditary endothelial dystrophy type II	SLC4A11	1	Congenital hereditary endothelial dystrophy II (CHED II) is a rare subtype of posterior corneal dystrophy (see this term) characterized by a diffuse ground-glass appearance of the corneas and marked corneal thickening from birth with nystagmus, and blurred vision.	Rare genetic eye disease
Orphanet:811	Shwachman-Diamond syndrome	SBDS;EFL1;SRP54;DNAJC21	4	Shwachman-Diamond syndrome (SDS) is a rare multisystemic syndrome characterized by chronic and usually mild neutropenia, pancreatic exocrine insufficiency associated with steatorrhea and growth failure, skeletal dysplasia with short stature, and an increased risk of bone marrow aplasia or leukemic transformation.	Inherited cancer-predisposing syndrome;Rare genetic hematologic disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic immune disease;Rare genetic gastroenterological disease
Orphanet:293150	Familial clubfoot due to PITX1 point mutation	PITX1	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:293144	Familial clubfoot due to 5q31 microdeletion	PITX1	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:741	Familial mitral valve prolapse	DCHS1	1	NA	Rare genetic developmental defect during embryogenesis
Orphanet:293168	Infantile-onset ascending hereditary spastic paralysis	ALS2	1	Infantile-onset ascending hereditary spastic paralysis (IAHSP) is a very rare motor neuron disease characterized by severe spasticity of the lower limbs in early life, progression of spasticity to the upper limbs in late childhood, and dysarthria.	Rare genetic neurological disorder
Orphanet:293165	Skin fragility-woolly hair-palmoplantar keratoderma syndrome	DSP	1	Skin fragility-woolly hair-palmoplantar keratoderma syndrome is a rare, genetic, ectodermal dysplasia syndrome characterized by persistent skin fragility which manifests with blistering and erosions due to minimal trauma, woolly hair with variable alopecia, hyperkeratotic nail dysplasia, diffuse or focal palmoplantar keratoderma with painful fissuring, and no cardiac abnormalities. Perioral hyperkeratosis may also be associated.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:428	Autosomal dominant hypocalcemia	CASR;GNA11	2	A rare disorder of calcium homeostasis characterized by variable degrees of hypocalcemia with abnormally low levels of parathyroid hormone (PTH) and persistant normal or elevated calciuria.	Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic endocrine disease
Orphanet:293181	Malignant migrating focal seizures of infancy	SCN1A;SLC25A22;TBC1D24;PLCB1;KCNT1;SLC12A5	6	A rare, genetic, neonatal epilepsy syndrome disease characterized by onset in the first 6 months of life of almost continuous migrating polymorphous focal seizures with corresponding multifocal ictal electroencephalographic discharges, progressive deterioration of psychomotor development, and usually early mortality.	Rare genetic neurological disorder
Orphanet:393	46,XX testicular disorder of sex development	SOX9;SRY;SOX3;NR0B1;NR5A1	5	A rare disorder of sex development (DSD) associated with a 46, XX karyotype and characterized by male external genitalia, ranging from normal to atypical with associated testosterone deficiency.	Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease;Genetic infertility
Orphanet:293284	Tetrahydrobiopterin-responsive hyperphenylalaninemia/phenylketonuria	PAH	1	Tetrahydrobiopterin-responsive hyperphenylalaninemia/ phenylketonuria (BH4-responsive hyperphenylalaninemia/ phenylketonuria) is a form of phenylketonuria (PKU, see this term), an inborn error of amino acid metabolism, characterized by mild to moderate symptoms of PKU including impaired cognitive function, seizures, and behavioral and developmental disorders, and a marked reduction and normalization of elevated phenylalanine concentrations after oral loading with tetrahydrobiopterin (BH4; sapropterin dihydrochloride), an essential cofactor of phenylalanine hydroxylase.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:2394	Pyruvate dehydrogenase E3 deficiency	DLD	1	Pyruvate dehydrogenase E3 deficiency is a very rare subtype of pyruvate dehydrogenase deficiency (PDHD, see this term) characterized by either early-onset lactic acidosis and delayed development, later-onset neurological dysfunction or liver disease.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:2686	Cyclic neutropenia	ELANE	1	NA	Rare genetic immune disease
Orphanet:284804	Ocular albinism	AP3D1	1	NA	NA
Orphanet:284414	Glycerol kinase deficiency, adult form	GK	1	A rare form of glycerol kinase deficiency (GKD) characterized by pseudohypertriglyceridemia in otherwise healthy adults and diagnosed fortuitously.	Rare inborn errors of metabolism
Orphanet:284417	Phosphoserine aminotransferase deficiency	PSAT1	1	Phosphoserine aminotransferase deficiency is an extremely rare form of serine deficiency syndrome (see this term) characterized clinically in the two reported cases to date by acquired microcephaly, psychomotor retardation, intractable seizures and hypertonia.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:284426	Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency	LDHA	1	NA	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:284435	Glycogen storage disease due to lactate dehydrogenase H-subunit deficiency	LDHB	1	NA	Rare inborn errors of metabolism
Orphanet:284973	Marfan syndrome type 2	TGFBR2	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic systemic or rheumatologic disease;Rare genetic vascular disease;Rare genetic eye disease
Orphanet:284963	Marfan syndrome type 1	FBN1	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic systemic or rheumatologic disease;Rare genetic vascular disease;Rare genetic eye disease
Orphanet:284984	Aneurysm-osteoarthritis syndrome	SMAD3	1	A rare, genetic, systemic disease characterized by the presence of arterial aneurysms, tortuosity and dissection throughout the arterial tree, associated with early-onset osteoarthritis (predominantly affecting the spine, hands and/or wrists, and knees) and mild craniofacial dysmorphism (incl. long face, high forehead, flat supraorbital ridges, hypertelorism, malar hypoplasia and, a raphe, broad or bifid uvula), as well as mild skeletal and cutaneous anomalies. Joint abnormalities, such as osteochondritis dissecans and intervertebral disc degeneration, are frequently associated. Additonal cardiovascular anomalies may include mitral valve defects, congenital heart malformations, ventricular hypertrophy and atrial fibrillation.	Rare genetic systemic or rheumatologic disease;Rare genetic vascular disease
Orphanet:284979	Neonatal Marfan syndrome	FBN1	1	Neonatal Marfan syndrome is a rare, severe and life-threatening genetic disease, occuring during the neonatal period, characterized by classical Marfan syndrome manifestations in addition to facial dysmorphism (megalocornea, iridodonesis, ectopia lentis, crumpled ears, loose redundant skin giving a 'senile' facial appearance), flexion joint contractures, pulmonary emphysema, and a severe, rapidly progressive cardiovascular disease (including ascending aortic dilatation and severe mitral and/or tricuspid valve insufficiency). Additionally, skeletal manifestations (arachnodactyly, dolichostenomelia, pectus deformities) are also associated.	Rare genetic systemic or rheumatologic disease;Rare genetic vascular disease
Orphanet:289365	Familial vesicoureteral reflux	TNXB;ROBO2;SOX17	3	Familial vesicoureteral reflux is a rare, non-syndromic urogenital tract malformation characterized by the familial occurrence of retrograde flow of urine from the bladder into the ureter and sometimes the kidneys. Patients may be asymptomatic or may present with recurrent, sometimes febrile, urinary tract infections that, in case of acute pyelonephritis, may lead to serious complications (renal scarring, hypertension, renal failure). Spontaneous resolution of the disorder is possible.	Rare genetic urogenital disease
Orphanet:289377	Early-onset myopathy with fatal cardiomyopathy	TTN	1	NA	Rare genetic cardiac disease;Rare genetic neurological disorder
Orphanet:289380	Myosclerosis	COL6A2	1	Myosclerosis is a rare, genetic, non-dystrophic myopathy characterized by early, diffuse, progressive muscle and joint contractures that result in severe limitation of movement of axial, proximal, and distal joints, walking difficulties in early childhood and toe walking. Patients typically present thin, sclerotic muscles with a woody consistency, mild girdle and proximal limb weakness with moderate distal weakness and scoliosis. Muscle biopsy shows partial collagen VI deficiency at the myofiber basement membrane and absent collagen VI around most endomysial/perimysial capillaries.	Rare genetic neurological disorder
Orphanet:289290	Hypermethioninemia encephalopathy due to adenosine kinase deficiency	ADK	1	Hypermethioninemia encephalopathy due to adenosine kinase deficiency is a rare inborn error of metabolism disorder characterized by persistent hypermethioninemia with increased levels of S-adenosylmethionine and S-adenosylhomocysteine which manifests with encephalopathy, severe global developmental delay, mild to severe liver dysfunction, hypotonia and facial dysmorphism (most significant is frontal bossing, macrocephaly, hypertelorism and depressed nasal bridge). Epileptic seizures, hypoglycemia and/or cardiac defects (pulmonary stenosis, atrial and/or ventricular septal defect, coarctation of the aorta) may be associated. Clinical picture may range from neurological symptoms only to multi-organ involvement.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:289266	Early-onset epileptic encephalopathy and intellectual disability due to GRIN2A mutation	GRIN2A	1	Early-onset epileptic encephalopathy and intellectual disability due to GRIN2A mutation is a rare intellectual disability and epilepsy syndrome characterized by global developmental delay and mild to profound intellectual disability, multiple types of usually intractable focal and generalized seizures with variable abnormal EEG findings, and bilateral progressive parenchymal volume loss and thin corpus callosum on brain MRI.	Rare genetic neurological disorder
Orphanet:289307	Developmental delay due to methylmalonate semialdehyde dehydrogenase deficiency	ALDH6A1	1	Developmental delay due to methylmalonate semialdehyde dehydrogenase deficiency is a rare, genetic, inborn error of branched-chain amino acid metabolism disorder, with a highly variable clinical and biochemical phenotype, typically characterized by mild to severe global developmental delay, elevated methylmalonic acid and, occasionally, lactic acid plasma levels, and chronic methylmalonic aciduria, which may be accompanied by elevation of additional organic or amino acids in urine (e.g. beta-alanine, methionine, 3-hydroxypropionic, 3-aminoisobutyric and/or 3-hydroxyisobutyric acid). Microcephaly, mild craniofacial dysmorphism, axial hypotonia, liver failure, and central nervous system abnormalities on MRI have also been reported.	Rare inborn errors of metabolism
Orphanet:289504	Combined malonic and methylmalonic acidemia	ACSF3	1	Combined malonic and methylmalonic acidemia is a rare inborn error of metabolism characterized by elevation of malonic acid (MA) and methylmalonic acid (MMA) in body fluids, with higher levels of MMA than MA. CMAMMA presents in childhood with metabolic acidosis, developmental delay, dystonia and failure to thrive or in adulthood with seizures, memory loss and cognitive decline.	Rare inborn errors of metabolism
Orphanet:289499	Congenital cataract microcornea with corneal opacity	PXDN;ATOH7	2	NA	Rare genetic eye disease
Orphanet:289527	OBSOLETE: Fatal infantile hypertrophic cardiomyopathy due to mitochondrial complex I deficiency	NDUFAF1	1	NA	NA
Orphanet:289465	Isolated congenital adermatoglyphia	SMARCAD1	1	Isolated congenital adermatoglyphia is a rare, genetic developmental defect during embryogenesis disorder characterized by the lack of epidermal ridges on the palms and soles, resulting in the absence of fingerprints, with no other associated manifestations. It is associated with a reduced number of sweat gland openings and reduced transpiration of palms and soles.	Rare genetic developmental defect during embryogenesis
Orphanet:289176	Autosomal recessive hypophosphatemic rickets	DMP1;ENPP1	2	A rare hereditary renal phosphate-wasting disorder characterized by hypophosphatemia, rickets and/or osteomalacia and slow growth.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic endocrine disease;Rare genetic renal disease
Orphanet:289157	Hypocalcemic vitamin D-dependent rickets	CYP27B1;CYP2R1	2	Hypocalcemic vitamin D-dependent rickets (VDDR-I) is an early-onset hereditary vitamin D metabolism disorder characterized by severe hypocalcemia leading to osteomalacia and rachitic bone deformations, and moderate hypophosphatemia.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic endocrine disease
Orphanet:281090	Syndromic recessive X-linked ichthyosis	STS	1	Syndromic recessive X-linked ichthyosis (RXLI) refers to the cases of RXLI (see this term) that are associated with extracutaneous manifestations as part of a syndrome.	Rare genetic skin disease
Orphanet:281190	Congenital reticular ichthyosiform erythroderma	KRT1;KRT10	2	NA	Rare genetic skin disease
Orphanet:281201	Keratosis linearis-ichthyosis congenita-sclerosing keratoderma syndrome	POMP	1	Keratosis linearis-ichthyosis congenita-sclerosing keratoderma syndrome is an inherited epidermal disorder characterized by palmoplantar keratoderma, linear hyperkeratotic papules on the flexural side of large joints (cord-like distribution around wrists, in antecubital and popliteal folds), hyperkeratotic plaques (on neck, axillae, elbows, wrists, and knees), mild ichthyosiform scaling, and sclerotic constrictions around fingers that present flexural deformities.	Rare genetic skin disease
Orphanet:281139	Annular epidermolytic ichthyosis	KRT10;KRT1	2	A rare clinical variant of epidermolytic ichthyosis (EI) characterized by the presence of a blistering phenotype at birth and the development from early infancy of annular polycyclic erythematous scales on the trunk and extremities.	Rare genetic skin disease
Orphanet:281122	Self-improving collodion baby	ALOX12B;ALOXE3;TGM1	3	Self-healing collodion baby (SHCB) is a minor variant of autosomal recessive congenital ichthyosis (ARCI; see this term) characterized by the presence of a collodion membrane at birth that heals within the first weeks of life.	Rare genetic skin disease;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:281127	Acral self-healing collodion baby	TGM1	1	A variant of self-healing collodion baby (SHCB) characterized by the presence at birth of a collodion membrane only at the extremities.	Rare genetic skin disease;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:280628	Familial progressive hyper- and hypopigmentation	KITLG	1	Familial progressive hyper- and hypopigmentation is a rare, genetic, skin pigmentation anomaly disorder characterized by progressive, diffuse, partly blotchy, hyperpigmented lesions that are intermixed with multiple café-au-lait spots, hypopigmented maculae and lentigines and are located on the face, neck, trunk and limbs, as well as, frequently, the palms, soles and oral mucosa. Dispigmentation pattern can range from well isolated café-au-lait/hypopigmented patches on a background of normal-appearing skin to confetti-like or mottled appearance.	Rare genetic skin disease
Orphanet:280633	Multiple congenital anomalies-hypotonia-seizures syndrome	PIGN	1	A rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by severe global developmental delay, hypotonia, and early-onset seizures, associated with multiple congenital anomalies, such as cardiac (e.g. patent foramen ovale, atrial septal defect, patent ductus arteriosus), genitourinary (i.e. hydrocele, renal collecting system dilatation, hydroureter, hydronephrosis, hypertrophic trabecular urinary bladder) and gastrointestinal (incl. gastroesophageal reflux, anal stenosis, imperforate anus, ano-vestibular fistula) abnormalities, as well as facial dysmorphism which includes coarse facies, a prominent occiput, bitemporal narrowing, epicanthal folds, hypertelorism, nystagmus/strabismus/wandering eyes, low-set, large ears with auricle abnormalities, depressed nasal bridge, upturned nose, long philtrum, large, open mouth with thin lips, high-arched palate, and micro/retrognathia.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:280615	Hemoglobinopathy Toms River	HBG2	1	Hemoglobinopathy Toms River is a rare, genetic hemoglobinopathy disorder, due to a defect in the gama subunit of the fetal hemoglobin, characterized by neonatal cyanosis, low hemoglobin oxygen saturation levels without arterial hypoxemia, moderate anemia and reticulocytosis, not associated with heart or lung disease. Symptoms progressively subside within the first months of life.	Rare genetic hematologic disease
Orphanet:280598	Hereditary sensorimotor neuropathy with hyperelastic skin	FBLN5	1	Hereditary sensorimotor neuropathy with hyperelastic skin is a rare, genetic, demyelinating hereditary motor and sensory neuropathy disorder characterized by slowly progressive, mild to moderate, distal muscle weakness and atrophy of the upper and lower limbs and variable distal sensory impairment, associated with variable hyperextensible skin and age-related macular degeneration. Hypermobility of distal joints, high palate, and minor skeletal abnormalities (e.g. pectus excavatus, dolichocephaly) may also be associated.	Rare genetic neurological disorder
Orphanet:280620	Progressive myoclonic epilepsy type 6	GOSR2	1	A rare, genetic, neurological disorder characterized by early-onset, progressive ataxia associated with myoclonic seizures (frequently associated with other seizure types such as generalized tonic-clonic, absence and drop attacks), scoliosis of variable severity, areflexia, elevated creatine kinase serum levels, and relative preservation of cognitive function until late in the disease course.	Rare genetic neurological disorder
Orphanet:280663	Hermansky-Pudlak syndrome type 9	BLOC1S6	1	NA	Rare inborn errors of metabolism;Rare genetic eye disease;Rare genetic skin disease;Rare genetic hematologic disease;Rare genetic immune disease
Orphanet:280671	Megaconial congenital muscular dystrophy	CHKB	1	A rare, genetic, skeletal muscle disease characterized by an early-onset hypotonia, muscle weakness, global developmental delay with intellectual disability, and cardiomyopathy. Congenital structural heart defects and ichthyosiform cutaneous lesions have also been associated. Muscle biopsy shows characteristic enlarged mitochondria located at the periphery of muscle fibers.	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:280640	Occipital pachygyria and polymicrogyria	LAMC3	1	Occipital pachygyria and polymicrogyria is a rare, genetic, cerebral malformation characterized by the presence of cortical smoothening with loss of secondary and tertiary gyri, associated with an excessive number of small, irregular gyri with increased cortical thickness, located in the occipital lobes. Patients usually present with seizures (including myoclonic-astatic, absence, atypical absence, vision loss, myoclonic-atonic, generalized tonic-clonic) and variable (absent to moderate) developmental and/or intellectual delay.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:280654	Autosomal recessive nail dysplasia	FZD6	1	Autosomal recessive nail dysplasia is a rare, isolated nail anomaly characterized by claw-shaped, thick, hyperplastic, hard and hyperpigmented nails, subungual hyperkeratosis, onycholysis and slow nail growth. Variable degree of disease severity has been reported.	Rare genetic skin disease
Orphanet:280651	Acrodysostosis with multiple hormone resistance	PRKAR1A;PDE4D	2	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic endocrine disease
Orphanet:280785	Bullous diffuse cutaneous mastocytosis	KIT	1	Bullous diffuse cutaneous mastocytosis (BDCM) is a form of diffuse cutaneous mastocytosis (DCM; see this term) characterized by generalized erythroderma and severe blistering associated with the accumulation of mast cells in the skin.	
Orphanet:280794	Pseudoxanthomatous diffuse cutaneous mastocytosis	KIT	1	Pseudoxanthomatous diffuse cutaneous mastocytosis (PDCM) is a rare form of diffuse cutaneous mastocytosis (DCM; see this term) characterized by yellow-orange infiltrated and xanthogranuloma-like lesions with only limited blistering.	
Orphanet:280679	Moyamoya angiopathy-short stature-facial dysmorphism-hypergonadotropic hypogonadism syndrome	BRCC3	1	Moyamoya angiopathy - short stature - facial dysmorphism - hypergonadotropic hypogonadism is a very rare, hereditary, neurological, dysmorphic syndrome characterized by moyamoya disease, short stature of postnatal onset, and stereotyped facial dysmorphism.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare genetic endocrine disease;Genetic infertility
Orphanet:280763	Severe intellectual disability and progressive spastic paraplegia	AP4M1;AP4E1;AP4B1;AP4S1	4	Severe intellectual disability and progressive spastic paraplegia is a rare complex spastic paraplegia characterized by an early onset hypotonia that progresses to spasticity, global developmental delay, severe intellectual disability and speech impairment, microcephaly, short stature and dysmorphic features. Patients often become non-ambulatory, and some develop seizures and stereotypic laughter.	Rare genetic neurological disorder
Orphanet:284149	Craniosynostosis-dental anomalies	IL11RA	1	Craniosynostosis-dental anomalies is a rare, genetic, cranial malformation syndrome characterized by premature fusion of multiple or all calvarial sutures (resulting in variable abnormal shape of the head), midface hypoplasia, delayed and ectopic tooth eruption and supernumerary teeth. Associated facial dysmorphism includes proptosis, hypertelorism, beaked nose, and relative prognathism. Variable digital anomalies (e.g. finger and/or toe syndactyly, clinodactyly), short stature, cognitive and/or motor delay, high palate, ear deformity and conductive hearing loss have also been reported.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:284139	Larsen-like syndrome, B3GAT3 type	B3GAT3	1	Larsen-like syndrome, B3GAT3 type is a rare, genetic, primary bone dysplasia characterized by laxity, dislocations and contractures of the joints, short stature, foot deformities (e.g. clubfeet), broad tips of fingers and toes, short neck, dysmorphic facial features (hypertelorism, downslanting palpebral fissures, upturned nose with anteverted nares, high arched palate) and various cardiac malformations. Severe disease is associated with multiple fractures, osteopenia, arachnodactyly and blue sclerae. A broad spectrum of additional features, including scoliosis, radio-ulnar synostosis, mild developmental delay, and various eye disorders (glaucoma, amblyopia, hyperopia, astigmatism, ptosis), are also reported.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare inborn errors of metabolism;Rare genetic cardiac disease
Orphanet:284169	Facial dysmorphism-developmental delay-behavioral abnormalities syndrome due to 10p11.21p12.31 microdeletion	WAC	1	Facial dysmorphism-developmental delay-behavioral abnormalities syndrome due to 10p11.21p12.31 microdeletion is a rare, genetic syndromic intellectual disability characterized by developmental delay, hypotonia, speech delay, mild to moderate intellectual disability, abnormal behavior (autistic, aggressive, hyperactive) and dysmorphic facial features, including synophrys or thick eyebrows, deep set eyes, bulbous nasal tip and full cheeks. Congenital heart and brain anomalies, visual and hearing impairment are also common.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare chromosomal anomaly
Orphanet:284247	Familial retinal arterial macroaneurysm	IGFBP7	1	Familial retinal arterial macroaneurysm is a rare, genetic cardiac disease characterized by an early onset of retinal artery macroaneurysms formation and concomitant supravalvular pulmonic stenosis, often requiring surgical correction.	Rare genetic cardiac disease;Rare genetic eye disease;Rare genetic neurological disorder
Orphanet:284232	Autosomal dominant Charcot-Marie-Tooth disease type 2O	DYNC1H1	1	A rare, genetic, subtype of autosomal dominant Charcot-Marie-Tooth disease type 2 characterized by early childhood-onset of slowly progressive, predominantly distal, lower limb muscle weakness and atrophy, delayed motor development, variable sensory loss, and pes cavus in the presence of normal or near-normal nerve conduction velocities. Additional variable features may include proximal muscle weakness, abnormal gait, arthrogryposis, scoliosis, cognitive impairment, and spasticity.	Rare genetic neurological disorder
Orphanet:284271	Autosomal recessive cerebellar ataxia-psychomotor delay syndrome	SYT14	1	A rare, hereditary, cerebellar ataxia disorder characterized by late-onset spinocerebellar ataxia, manifesting with slowly progressive gait disturbances, dysarthria, limb and truncal ataxia, and smooth-pursuit eye movement disturbance, associated with a history of psychomotor delay from childhood. Mild atrophy of the cerebellar vermis and hemispheres is observed on brain imaging.	Rare genetic neurological disorder
Orphanet:284324	Childhood-onset autosomal recessive slowly progressive spinocerebellar ataxia	TPP1	1	A rare, genetic, autosomal recessive cerebellar ataxia disease characterized by slowly progressive spinocerebellar ataxia developing during childhood, manifesting with gait and limb ataxia, postural tremor, dysarthria, sensory alterations (e.g. decreased vibration sense), eye movement anomalies (i.e. nystagmus, saccadic pursuit, oculomotor apraxia), upper and lower limb fasciculations, and hyperreflexia with Babinski signs. Brain imaging reveals cerebellar, pontine, vermian and medullar atrophy.	Rare genetic neurological disorder
Orphanet:284282	Autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome due to WWOX deficiency	WWOX	1	A rare autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome characterized by early-childhood onset of cerebellar ataxia associated with generalized tonic-clonic epilepsy and psychomotor development delay, dysarthria, gaze-evoked nystagmus and learning disability. Other features in some patients include upper motor neuron signs with leg spasticity and extensor plantar responses, and mild cerebellar atrophy on brain MRI.	Rare genetic neurological disorder
Orphanet:284289	Adult-onset autosomal recessive cerebellar ataxia	ANO10	1	A rare, genetic, autosomal recessive cerebellar ataxia disease characterized by adulthood-onset of slowly progressive spinocerebellar ataxia, manifesting with gait and appendicular ataxia, dysarthria, ocular movement anomalies (e.g. horizontal, vertical, and/or downbeat nystagmus, hypermetric saccades), increased deep tendon reflexes and progressive cognitive decline. Additional variable features may include proximal leg muscle wasting and fasciculations, pes cavus, inspiratory stridor, epilepsy, retinal degeneration and cataracts. Brain imaging reveals marked cerebellar atrophy and electromyography shows evidence of lower motor neuron involvement.	Rare genetic neurological disorder
Orphanet:284343	Pleuropulmonary blastoma familial tumor susceptibility syndrome	DICER1	1	NA	
Orphanet:284339	Pontocerebellar hypoplasia type 7	TOE1	1	Pontocerebellar hypoplasia type 7 (PCH7) is a novel very rare form of pontocerebellar hypoplasia (see this term) with unknown etiology and poor prognosis reported in four patients and is characterized clinically during the neonatal period by hypotonia, no palpable gonads, micropenis and from infancy by progressive microcephaly, apneic episodes, poor feeding, seizures and regression of penis. MRI demonstrates a pontocerebellar hypoplasia. PCH7 is expressed as PCH with 46,XY disorder of sex development (see this term) in individuals with XY karyotype, and may be expressed as PCH only in individuals with XX karyotype.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:284408	Glycerol kinase deficiency, infantile form	GK	1	Infantile glycerol kinase deficiency (GKD) is a severe form of GKD (see this term) characterized clinically by poor feeding, failure to thrive, salt-wasting dehydration, vomiting, Addisonian pigmentation, hypotonia, and disorders of consciousness. Some patients have complex GKD associated with adrenal hypoplasia congenita and/or Duchenne muscular dystrophy (DMD) (see these terms) with manifestations including intellectual deficit, dysmorphic facial features, abnormal external genitalia, strabismus, seizures, and progressive lethargy.	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:284411	Glycerol kinase deficiency, juvenile form	GK	1	Juvenile glycerol kinase deficiency (GKD) is an uncommon form of GKD (see this term) characterized by Reye-like clinical manifestations including episodic vomiting, acidemia, and disorders of consciousness.	Rare inborn errors of metabolism
Orphanet:282166	Inherited Creutzfeldt-Jakob disease	PRNP	1	Inherited or familial Creutzfeldt-Jakob disease (fCJD) is a very rare form of genetic prion disease (see this term) characterized by typical CJD features (rapidly progressive dementia, personality/behavioral changes, psychiatric disorders, myoclonus, and ataxia) with a genetic cause and sometimes a family history of dementia.	Rare genetic neurological disorder
Orphanet:284102	NA	IFNL3;IFNL4	2	NA	NA
Orphanet:284113	NA	ITPA	1	NA	NA
Orphanet:284121	NA	CYP1A2;COMT	2	NA	NA
Orphanet:309854	Cirrhosis-dystonia-polycythemia-hypermanganesemia syndrome	SLC30A10	1	NA	Rare genetic hepatic disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:309803	Rhizomelic chondrodysplasia punctata type 3	AGPS	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:309789	Rhizomelic chondrodysplasia punctata type 1	PEX7	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:309796	Rhizomelic chondrodysplasia punctata type 2	GNPAT	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:314029	High bone mass osteogenesis imperfecta	COL1A1;COL1A2;BMP1	3	High bone mass osteogenesis imperfecta is a rare, genetic, primary bone dysplasia disorder characterized by increased bone fragility, manifesting with mutiple, childhood-onset, vertebral and peripheral fractures, associated with increased bone mass density on radiometric examination. Patients typically present normal or mild short stature and dentinogenesis, hearing, and sclerae are commonly normal.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:314022	Gastric adenocarcinoma and proximal polyposis of the stomach	APC	1	Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a rare hereditary gastric cancer characterized by proximal gastric polyposis and increased risk of early-onset, intestinal-type adenocarcinoma of the gastric body, with no duodenal or colorectal polyposis.	
Orphanet:313892	Developmental and speech delay due to SOX5 deficiency	SOX5	1	Developmental and speech delay due to SOX5 deficiency is a rare genetic syndromic intellectual disability characterized by mild to severe global developmental delay, intellectual disability and behavioral abnormalities, hypotonia, strabismus, optic nerve hypoplasia and mild facial dysmorphic features (down slanting palpebral fissures, frontal bossing, crowded teeth, auricular abnormalities and prominent philtral ridges). Other associated clinical features may include seizures and skeletal anomalies (kyphosis/scoliosis, pectus deformities).	Rare genetic neurological disorder
Orphanet:313884	12p12.1 microdeletion syndrome	SOX5	1	12p12.1 microdeletion syndrome is a rare chromosomal anomaly syndrome, resulting from the partial deletion of the short arm of chromosome 12, characterized by intellectual disability, global developmental delay with prominent language impairment, behavioral abnormalities and mild facial dysmorphism (incl. frontal bossing, downslanting palpebral fissures, epicanthal folds, broad, depressed nasal bridge with bulbous nasal tip, low-set ears with underdeveloped helices). Other associated features may include skeletal abnormalities (butterfly vertebrae, scoliosis), strabismus, optic nerve hypoplasia, and brain malformations.	Rare genetic neurological disorder;Rare chromosomal anomaly
Orphanet:313855	FGFR2-related bent bone dysplasia	FGFR2	1	FGFR2-related bent bone dysplasia is a rare, genetic, lethal, primary bone dysplasia characterized by dysmorphic craniofacial features (low-set, posteriorly rotated ears, hypertelorism, megalophtalmos, flattened and hypoplastic midface, micrognathia), hypomineralization of the calvarium, craniosynostosis, hypoplastic clavicles and pubis, and bent long bones (particularly involving the femora), caused by germline mutations in the FGFR2 gene. Prematurely erupted fetal teeth, osteopenia, hirsutism, clitoromegaly, gingival hyperplasia, and hepatosplenomegaly with extramedullary hematopoesis may also be associated.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:313850	Infantile cerebellar-retinal degeneration	ACO2	1	Infantile cerebellar-retinal degeneration is a rare, neurodegenerative disorder characterized by an early onset of truncal hypotonia, variable forms of seizures, athetosis, severe global developmental delay, intellectual disability and various ophthalmologic abnormalities, including strabismus, nystagmus, optic atrophy and retinal degeneration.	Rare genetic neurological disorder;Rare genetic eye disease;Rare inborn errors of metabolism
Orphanet:313846	Familial cutaneous telangiectasia and oropharyngeal cancer predisposition syndrome	ATR	1	Familial cutaneous telangiectasia and oropharyngeal cancer predisposition syndrome is a rare, inherited cancer-predisposing syndrome characterized by an early development of cutaneous telangiectasia, mild dental and nail anomalies, patchy alopecia over the affected skin areas and increased lifetime risk for oropharyngeal cancer. Other types of cancer have also been reported.	Rare genetic skin disease
Orphanet:313838	Coats plus syndrome	CTC1;STN1	2	Coats plus syndrome is a pleiotropic multisystem disorder characterized by retinal telangiectasia and exudates, intracranial calcification with leukoencephalopathy and brain cysts, osteopenia with predisposition to fractures, bone marrow suppression, gastrointestinal bleeding and portal hypertension. It is transmitted as an autosomal recessive disease.	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:313808	Hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented glia	AARS2;CSF1R	2	Hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented glia is a rare autosomal dominant disease characterized by a complex phenotype including progressive dementia, apraxia, apathy, impaired balance, parkinsonism, spasticity and epilepsy.	Rare genetic neurological disorder
Orphanet:313795	Jawad syndrome	RBBP8	1	Jawad syndrome is a rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by congenital microcephaly wih facial dysmorphism (sloping forehead, prominent nose, mild retrognathia), moderate to severe, non-progressive intellectual disability and symmetrical digital malformations of variable degree, including brachydactyly of the fifth fingers with single flexion crease, clinodactyly, syndactyly, polydactyly and hallux valgus. Congenital anonychia and white café au lait-like spots on the skin of hands and feet are also associated.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:313772	Early-onset spastic ataxia-myoclonic epilepsy-neuropathy syndrome	AFG3L2	1	Early-onset spastic ataxia-myoclonic epilepsy-neuropathy syndrome is a rare hereditary spastic ataxia disorder characterized by childhood onset of slowly progressive lower limb spastic paraparesis and cerebellar ataxia (with dysarthria, swallowing difficulties, motor degeneration), associated with sensorimotor neuropathy (including muscle weakness and distal amyotrophy in lower extremities) and progressive myoclonic epilepsy. Ocular signs (ptosis, oculomotor apraxia), dysmetria, dysdiadochokinesia, dystonic movements and myoclonus may also be associated.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic gastroenterological disease
Orphanet:314603	Autosomal recessive spastic ataxia with leukoencephalopathy	MARS2	1	A rare, genetic, autosomal recessive spastic ataxia disease characterized by cerebellar ataxia, spasticity, cerebellar (and in some cases cerebral) atrophy, dystonia, and leukoencephalopathy.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:314597	Chudley-McCullough syndrome	GPSM2	1	Chudley-McCullough syndrome is a rare, genetic, syndromic deafness characterized by severe to profound, bilateral, sensorineural hearing loss (congenital or rapidly progressive in infancy) associated with a complex brain malformation including hydrocephalus, varying degrees of partial corpus callosum agenesis, colpocephaly, cerebral and cerebellar cortical dysplasia (bilateral medial frontal polymicrogyria, bilateral frontal subcortical heteropia) and, in some, arachnoid cysts. Major physical abnormalities or psychomotor delay are usually not associated.	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:314485	Young adult-onset distal hereditary motor neuropathy	DNAJB2	1	Young adult-onset distal hereditary motor neuropathy is a rare autosomal recessive distal hereditary motor neuropathy characterized by slowly progressive muscular weakness, hypotonia and atrophy of the lower limbs, more pronounced distally, leading to paralysis, and loss of tendon reflexes. Additional features may include pes cavus and mild dysphonia. The upper limbs are relatively spared.	Rare genetic neurological disorder
Orphanet:314555	Craniofacial dysplasia-osteopenia syndrome	IRX5	1	Craniofacial dysplasia-osteopenia syndrome is a rare, genetic developmental defect during embryogenesis disorder characterized by craniofacial dysmorphism (incl. brachycephaly, prominent forehead, sparse lateral eyebrows, severe hypertelorism, upslanting palpebral fissures, epicanthal folds, protruding ears, broad nasal bridge, pointed nasal tip, flat philtrum, anteverted nostrils, large mouth, thin upper vermilion border, highly arched palate and mild micrognathia) associated with osteopenia leading to repeated long bone fractures, severe myopia, mild to moderate sensorineural or mixed hearing loss, enamel hypoplasia, sloping shoulders and mild intellectual disability.	Rare genetic developmental defect during embryogenesis
Orphanet:314394	Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome	POC1A	1	Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome is a rare, genetic, primary bone dysplasia disorder characterized by severe pre- and post-natal short stature, facial dysmorphism (incl.dolicocephaly, long triangular face, tall forehead, down-slanting palpebral fissures, prominent nose, long philtrum, small ears), early-onset or postpubertal sparse, short hair and hypoplastic fingernails. Small hands with tapering fingers, bracydactyly and fifth-finger clinodactyly, as well as a high-pitched voice are also associated.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:314399	Autosomal dominant aplasia and myelodysplasia	SRP72	1	A rare, genetic, hematologic disorder characterized by bone marrow failure which manifests with aplastic anemia and/or myelodysplasia, associated with hearing/ear abnormalities (such as deafness, labyrinthitis), inherited in an autosomal dominant manner.	Rare genetic hematologic disease
Orphanet:314404	Autosomal dominant cerebellar ataxia-deafness-narcolepsy syndrome	DNMT1	1	A rare polymorphic disorder, subtype of autosomal dominant cerebellar ataxia type 1 (ADCA type 1), characterized by ataxia, sensorineural deafness and narcolepsy with cataplexy and dementia.	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder
Orphanet:314373	Chronic infantile diarrhea due to guanylate cyclase 2C overactivity	GUCY2C	1	A rare, genetic, intestinal disease characterized by early-onset, chronic diarrhea and intestinal inflammation due to overactivity of guanylate cyclase 2C. Additional manifestations include meteorism, dehydration, metabolic acidosis and electrolyte disturbances. Intestinal dysmotility, small-bowel obstruction and esophagitis (with or without esophageal hernia), as well as irritable bowel syndrome (without severe abdominal pain) and Crohn's disease, are frequently associated.	Rare genetic gastroenterological disease
Orphanet:314376	Intestinal obstruction in the newborn due to guanylate cyclase 2C deficiency	GUCY2C	1	 gene (12p12) leading to marked reduction or absence of enzymatic activity of guanylate cyclase 2C were found in the affected patients. The disease was reported to show partial penetrance.	Rare genetic gastroenterological disease
Orphanet:314381	Hereditary sensory and autonomic neuropathy type 6	DST	1	NA	Rare genetic neurological disorder
Orphanet:314051	Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome	EARS2	1	Leukoencephalopathy-thalamus and brainstem anomalies-high lactate (LTBL) syndrome is a rare, genetic neurological disorder defined by early-onset of neurologic symptoms, biphasic clinical course, unique MRI features (incl. extensive, symmetrical, deep white matter abnormalities), and increased lactate in body fluids. The severe form is characterized by delayed psychomotor development, seizures, early-onset hypotonia, and persistently increased lactate levels. The mild form usually presents with irritability, psychomotor regression after six months of age, and temporary high lactate levels, with overall clinical improvement from the second year onward.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:306674	Kufor-Rakeb syndrome	ATP13A2	1	Kufor-Rakeb syndrome (KRS) is a rare genetic neurodegenerative disorder characterized by juvenile Parkinsonism, pyramidal degeneration (dystonia), supranuclear palsy, and cognitive impairment.	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:306734	Primary dystonia, DYT21 type	DYT21	1	Primary dystonia, DYT21 type is a subtype of mixed dystonia with a late-onset form of pure torsion dystonia.	Rare genetic neurological disorder
Orphanet:308380	Methylcobalamin deficiency type cblDv1	MMADHC	1	NA	Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic hematologic disease
Orphanet:308386	Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A	MOCS1	1	NA	Rare inborn errors of metabolism
Orphanet:308393	Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B	MOCS2	1	NA	Rare inborn errors of metabolism
Orphanet:308400	Sulfite oxidase deficiency due to molybdenum cofactor deficiency type C	GPHN	1	NA	Rare inborn errors of metabolism
Orphanet:308410	Autism-epilepsy syndrome due to branched chain ketoacid dehydrogenase kinase deficiency	BCKDK	1	A rare disorder of branched-chain amino acid metabolism characterized by childhood-onset epilepsy, autism and intellectual disability with reduced levels of plasma branched chain aminoacids.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:308425	Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency	MCEE	1	Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency is a rare inborn error of metabolism disease characterized by mild to moderate, persistent elevation of methylmalonic acid in plasma, urine and cerebrospinal fluid. Clinical presentation may include acute metabolic decompensation with metabolic acidosis (presenting with vomiting, dehydration, confusion, hallucinations), nonspecific neurological symptoms, or may also be asymptomatic.	Rare inborn errors of metabolism
Orphanet:308698	Glycogen storage disease due to glycogen branching enzyme deficiency, childhood neuromuscular form	GBE1	1	NA	Rare genetic hepatic disease;Rare genetic cardiac disease;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:308712	Glycogen storage disease due to glycogen branching enzyme deficiency, adult neuromuscular form	GBE1	1	NA	Rare genetic hepatic disease;Rare genetic cardiac disease;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:308670	Glycogen storage disease due to glycogen branching enzyme deficiency, congenital neuromuscular form	GBE1	1	NA	Rare genetic hepatic disease;Rare genetic cardiac disease;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:308684	Glycogen storage disease due to glycogen branching enzyme deficiency, childhood combined hepatic and myopathic form	GBE1	1	NA	Rare genetic hepatic disease;Rare genetic cardiac disease;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:309015	Familial lipoprotein lipase deficiency	LPL	1	NA	Rare inborn errors of metabolism;Rare genetic endocrine disease
Orphanet:309020	Familial apolipoprotein C-II deficiency	APOC2	1	NA	Rare inborn errors of metabolism;Rare genetic endocrine disease
Orphanet:308487	Generalized galactose epimerase deficiency	GALE	1	NA	Rare genetic hepatic disease;Rare genetic eye disease;Rare inborn errors of metabolism;Rare genetic renal disease
Orphanet:308473	Erythrocyte galactose epimerase deficiency	GALE	1	NA	Rare genetic hepatic disease;Rare genetic eye disease;Rare inborn errors of metabolism;Rare genetic renal disease
Orphanet:178	Chordoma	TBXT	1	Chordomas are rare malignant tumors arising from embryonic remnants of the notochord in axial skeleton.	Rare genetic tumor;Rare genetic endocrine disease
Orphanet:2637	Microcephalic osteodysplastic primordial dwarfism type II	PCNT	1	A rare bone disease and a form of microcephalic primordial dwarfism characterized by severe pre- and postnatal growth retardation, with marked microcephaly in proportion to body size, skeletal dysplasia, abnormal dentition, insulin resistance, and increased risk for cerebrovascular disease.	Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease;Rare genetic bone disease;Rare genetic neurological disorder
Orphanet:308442	Vitamin B12-responsive methylmalonic acidemia, type cblDv2	MMADHC	1	NA	Rare inborn errors of metabolism;Rare genetic renal disease
Orphanet:308655	Glycogen storage disease due to glycogen branching enzyme deficiency, fatal perinatal neuromuscular form	GBE1	1	NA	Rare genetic hepatic disease;Rare genetic cardiac disease;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:308638	Glycogen storage disease due to glycogen branching enzyme deficiency, non progressive hepatic form	GBE1	1	NA	Rare genetic hepatic disease;Rare genetic cardiac disease;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:308621	Glycogen storage disease due to glycogen branching enzyme deficiency, progressive hepatic form	GBE1	1	NA	Rare genetic hepatic disease;Rare genetic cardiac disease;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:308552	Glycogen storage disease due to acid maltase deficiency, infantile onset	GAA	1	Glycogen storage disease due to acid maltase deficiency, infantile onset is the most severe form of glycogen storage disease due to acid maltase deficiency, characterized by cardiomegaly with respiratory distress, muscle weakness and feeding difficulties. It is often fatal.	Rare genetic cardiac disease;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:309271	Metachromatic leukodystrophy, adult form	PSAP;ARSA	2	NA	Rare genetic neurological disorder;Rare genetic eye disease;Rare inborn errors of metabolism
Orphanet:309282	Alpha-mannosidosis, infantile form	MAN2B1	1	NA	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:309288	Alpha-mannosidosis, adult form	MAN2B1	1	NA	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:309246	GM2 gangliosidosis, AB variant	GM2A	1	GM2 gangliosidosis, AB variant is an extremely rare, severe genetic disorder characterized by progressive neurological decline due to ganglioside activator deficiency.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:309252	Atypical Gaucher disease due to saposin C deficiency	PSAP	1	NA	Rare inborn errors of metabolism
Orphanet:309256	Metachromatic leukodystrophy, late infantile form	PSAP;ARSA	2	NA	Rare genetic neurological disorder;Rare genetic eye disease;Rare inborn errors of metabolism
Orphanet:309263	Metachromatic leukodystrophy, juvenile form	PSAP;ARSA	2	NA	Rare genetic neurological disorder;Rare genetic eye disease;Rare inborn errors of metabolism
Orphanet:309324	Free sialic acid storage disease, infantile form	SLC17A5	1	NA	Rare genetic bone disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:309331	Intermediate severe Salla disease	SLC17A5	1	NA	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:309334	Salla disease	SLC17A5	1	NA	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:309297	Mucopolysaccharidosis type 4A	GALNS	1	NA	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:309310	Mucopolysaccharidosis type 4B	GLB1	1	NA	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:309185	Tay-Sachs disease, B variant, juvenile form	HEXA	1	NA	Rare genetic neurological disorder;Rare genetic eye disease;Rare inborn errors of metabolism
Orphanet:309178	Tay-Sachs disease, B variant, infantile form	HEXA	1	NA	Rare genetic neurological disorder;Rare genetic eye disease;Rare inborn errors of metabolism
Orphanet:309239	Tay-Sachs disease, B1 variant	HEXA	1	NA	Rare genetic neurological disorder;Rare genetic eye disease;Rare inborn errors of metabolism
Orphanet:309192	Tay-Sachs disease, B variant, adult form	HEXA	1	NA	Rare genetic neurological disorder;Rare genetic eye disease;Rare inborn errors of metabolism
Orphanet:309155	Sandhoff disease, infantile form	HEXB	1	NA	Rare genetic neurological disorder;Rare genetic eye disease;Rare inborn errors of metabolism
Orphanet:309169	Sandhoff disease, adult form	HEXB	1	NA	Rare genetic neurological disorder;Rare genetic eye disease;Rare inborn errors of metabolism
Orphanet:309162	Sandhoff disease, juvenile form	HEXB	1	NA	Rare genetic neurological disorder;Rare genetic eye disease;Rare inborn errors of metabolism
Orphanet:300547	Autosomal recessive infantile hypercalcemia	CYP24A1;SLC34A1	2	A rare, genetic, phosphocalcic metabolism disorder characterized by early-onset hypercalcemia, hypophosphatemia, hypercalciuria, decreased intact parathyroid hormone serum levels and medullary nephrocalcinosis, typically manifesting with failure to thrive, hypotonia, vomiting, constipation and/or polyuria.	Rare genetic renal disease;Rare genetic endocrine disease
Orphanet:300570	Cortical dysgenesis with pontocerebellar hypoplasia due to TUBB3 mutation	TUBB3	1	A rare, genetic, non-syndromic cerebral malformation due to abnormal neuronal migration disease characterized by the association of cortical dysplasia and pontocerebellar hypoplasia, manifesting with global developmental delay, mild to severe intellectual disability, axial hypotonia, strabismus, nystagmus and, occasionally, optic nerve hypoplasia. Brain imaging reveals variable malformations, including frontally predominant microgyria, gyral disorganization and simplification, dysmorphic and hypertrophic basal ganglia, cerebellar vermis dysplasia, brainstem/corpus callosum hypoplasia, and/or olfactory bulbs agenesis.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:300573	Polymicrogyria due to TUBB2B mutation	TUBB2B	1	A rare, genetic, central nervous system malformation characterized by generalized or focal polmicrogryia-like cortical dysplasia and simplified gyral pattern, or alternatively by microlissencephaly and agenesis of the corpus callosum. Clinical manifestations are variable and include microcephaly, seizures, hypotonia, developmental delay, severe psychomotor delay, ataxia, spastic diplegia or tetraplegia, and ocular abnormalities (strabismus, ptosis or optic atrophy).	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:300576	Oligodontia-cancer predisposition syndrome	AXIN2	1	Oligodontia-cancer predisposition syndrome is a rare, genetic, odontologic disease characterized by congenital absence of six or more permanent teeth (excluding the third molars) in association with an increased risk for malignancies, ranging from gastrointestinal polyposis to early-onset colorectal cancer and/or breast cancer. Ectodermal dysplasia (manifesting with sparse hair and/or eyebrows) may also be associated.	Inherited cancer-predisposing syndrome
Orphanet:300496	Multiple congenital anomalies-hypotonia-seizures syndrome type 2	PIGA	1	Multiple congenital anomalies-hypotonia-seizures syndrome type 2 is a rare, genetic, lethal, neurometabolic malformation syndrome characterized by multiple, variable, congenital cardiac (systolic murmur, atrial septal defect), urinary (duplicated collecting system, vesicoureteral reflux) and central nervous system (thin corpus callosum, cerebellar hypoplasia) malformations associated with neonatal hypotonia, early-onset epileptic encephalopathy, and myoclonic seizures. Craniofacial dysmorphism (prominent occiput, enlarged fontanel, fused metopic suture, upslanted palpebral fissures, overfolded helix, depressed nasal bridge, anteverted nose, malar flattening, microstomy with downturned corners, Pierre-Robin sequence, high arched palate, short neck) and other manifestions (joint contractures, hyperreflexia, dysplastic nails, developmental delay) are also observed.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:300525	Pseudohypoaldosteronism type 2D	KLHL3	1	NA	Rare genetic renal disease
Orphanet:300530	Pseudohypoaldosteronism type 2E	CUL3	1	NA	Rare genetic renal disease
Orphanet:300536	DDOST-CDG	DDOST	1	 (1p36.1).	Rare genetic hepatic disease;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:300865	Primary cutaneous anaplastic large cell lymphoma	TYK2;NPM1	2	Primary cutaneous anaplastic large cell lymphoma (C-ALCL) is a rare T-cell non-Hodgkin lymphoma that affects the skin and generally shows no extracutaneous involvement at presentation. It belongs to the spectrum of primary cutaneous CD30+ lymphoproliferative disorders along with lymphomatoid papulosis (see this term) with which it shares overlapping clinical and histopathologic features.	
Orphanet:300878	Hairy cell leukemia variant	IGHV4-34	1	Hairy Cell Leukemia variant (HCL-V) is defined as a rare and indolent form of small, mature, B-cell leukemia characterized by splenomegaly, an elevated white blood cell (WBC) count and hyper-cellular bone marrow. HCL-V is more aggressive and resistant to therapy than classical HCL (HCL-C) (see this term).	
Orphanet:300895	ALK-positive anaplastic large cell lymphoma	ALK	1	A type of ALCL, a rare and aggressive peripheral T-cell non-Hodgkin lymphoma affecting lymph nodes and extranodal sites, which is characterized by the expression of a protein called anaplastic lymphoma kinase (ALK).	
Orphanet:300605	Juvenile amyotrophic lateral sclerosis	ALS2;SPG11;FUS;SIGMAR1	4	Juvenile amyotrophic lateral sclerosis (JALS) is a very rare severe motor neuron disease characterized by progressive upper and lower motor neuron degeneration causing facial spasticity, dysarthria, and gait disorders with onset before 25 years of age.	Rare genetic neurological disorder
Orphanet:300751	Familial dilated cardiomyopathy with conduction defect due to LMNA mutation	LMNA	1	Familial dilated cardiomyopathy with conduction defect due to LMNA mutation is a rare familial dilated cardiomyopathy characterized by left ventricular enlargement and/or reduced systolic function preceded or accompanied by significant conduction system disease and/or arrhythmias including bradyarrhythmias, supraventricular or ventricular arrhythmias. Disease onset is usually in early to mid-adulthood. Sudden cardiac death may occur and may be the presenting symptom. In some cases, it is associated with skeletal myopathy and elevated serum creatine kinase.	Rare genetic cardiac disease;Laminopathy
Orphanet:306436	Congenital sucrase-isomaltase deficiency with starch intolerance	SI	1	NA	Rare inborn errors of metabolism;Rare genetic gastroenterological disease
Orphanet:306462	Congenital sucrase-isomaltase deficiency without starch intolerance	SI	1	NA	Rare inborn errors of metabolism;Rare genetic gastroenterological disease
Orphanet:306446	Congenital sucrase-isomaltase deficiency with minimal starch tolerance	SI	1	NA	Rare inborn errors of metabolism;Rare genetic gastroenterological disease
Orphanet:306550	FADD-related immunodeficiency	FADD	1	 gene (11q13.3) was found in the family and the disease is thought to follow an autosomal recessive pattern of inheritance.	Rare genetic immune disease
Orphanet:306542	Frontonasal dysplasia-severe microphthalmia-severe facial clefting syndrome	ALX1	1	Frontonasal dysplasia-severe microphthalmia-severe facial clefting syndrome is a rare, genetic, orofacial clefting malformation syndrome characterized by severe frontonasal dysplasia with complete cleft palate, facial cleft, extreme microphtalmia and hypertelorism, frequently associated with eyelid colobomata, sparse or absent eyelashes/eyebrows, wide nasal bridge with hypoplastic alae nasi, low-set, posteriorly rotated ears and caudal appendage in the sacral region.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:306547	Porencephaly-microcephaly-bilateral congenital cataract syndrome	JAM3	1	Porencephaly-microcephaly-bilateral congenital cataract syndrome is a rare, genetic, central nervous system malformation syndrome characterized by bilateral congenital cataracts and severe hemorrhagic destruction of the brain parenchyma with associated massive cystic degeneration, enlarged ventricles and subependymal calcification. Patients typically present generalized spasticity, increased deep tendon reflexes and seizures. Hepatomegaly and renal anomalies have also been reported.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:306530	Congenital hereditary facial paralysis-variable hearing loss syndrome	HOXB1	1	Congenital hereditary facial paralysis-variable hearing loss syndrome is an extremely rare autosomal recessive disorder characterized by bilateral facial palsy with masked facies, sensorineural hearing loss, dysmorphic features (midfacial retrusion, low-set ears), and strabismus.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:306507	LAMB2-related infantile-onset nephrotic syndrome	LAMB2	1	NA	Rare genetic renal disease
Orphanet:306511	Autosomal recessive spastic paraplegia type 48	AP5Z1	1	Autosomal recessive spastic paraplegia type 48 is a form of hereditary spastic paraplegia usually characterized by a pure phenotype of a slowly progressive spastic paraplegia associated with urinary incontinence with an onset in mid- to late-adulthood. A complex phenotype, with the additional findings of cognitive impairment, sensorimotor polyneuropathy, ataxia and parkinsonism, as well as thin corpus callosum and white matter lesions (seen on magnetic resonance imaging), has also been reported.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:306504	Junctional epidermolysis bullosa with respiratory and renal involvement	ITGA3	1	Congenital nephrotic syndrome-interstitial lung disease-epidermolysis bullosa syndrome is a life-threatening multiorgan disorder which develops in the first months of life, presenting with respiratory distress and proteinuria in the nephrotic range, and leading to severe interstitial lung disease and renal failure. Some patients additionally display cutaneous alterations, ranging from blistering and skin erosions to an epidermolysis bullosa-like phenotype, with toe nail dystrophy and sparse hair.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic respiratory disease;Rare genetic renal disease
Orphanet:306474	Congenital sucrase-isomaltase deficiency with starch and lactose intolerance	SI	1	NA	Rare inborn errors of metabolism;Rare genetic gastroenterological disease
Orphanet:306486	Congenital sucrase-isomaltase deficiency without sucrose intolerance	SI	1	NA	Rare inborn errors of metabolism;Rare genetic gastroenterological disease
Orphanet:306661	Familial hyperphosphatemic tumoral calcinosis/Hyperphosphatemic hyperostosis syndrome	FGF23;GALNT3;KL	3	Familial tumoral calcinosis (FTC) refers to a rare autosomal recessive disorder characterized by the occurrence of cutaneous and subcutaneous calcified masses, usually adjacent to large joints, such as hips, shoulders and elbows. FTC can occur in the setting of hyperphosphatemia or normophosphatemia, depending on the type of gene mutation involved.	Rare genetic tumor;Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic endocrine disease;Rare inborn errors of metabolism
Orphanet:306658	Familial normophosphatemic tumoral calcinosis	SAMD9	1	NA	Rare genetic tumor;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic endocrine disease
Orphanet:306617	X-linked complicated spastic paraplegia type 1	L1CAM	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:306597	X-linked Opitz G/BBB syndrome	MID1	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic urogenital disease
Orphanet:306588	Autosomal dominant Opitz G/BBB syndrome	SPECC1L	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic urogenital disease
Orphanet:306577	Sodium channelopathy-related small fiber neuropathy	SCN9A;SCN10A;SCN11A	3	#64257;ber density. Large fiber functions (i.e. normal strength, tendon reflexes, and vibration sense) and nerve conduction studies are typically normal.	Rare genetic neurological disorder
Orphanet:306558	Primary microcephaly-epilepsy-permanent neonatal diabetes syndrome	IER3IP1	1	Primary microcephaly-epilepsy-permanent neonatal diabetes syndrome is a rare, genetic, neurologic disease characterized by congenital microcephaly, severe, early-onset epileptic encephalopathy (manifesting as intractable, myoclonic and/or tonic-clonic seizures), permanent, neonatal, insulin-dependent diabetes mellitus, and severe global developmental delay. Muscular hypotonia, skeletal abnormalities, feeding difficulties, and dysmorphic facial features (including narrow forehead, anteverted nares, small mouth with deep philtrum, tented upper lip vermilion) are frequently associated. Brain MRI reveals cerebral atrophy with cortical gyral simplification and aplasia/hypoplasia of the corpus callosum.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease
Orphanet:295195	Synpolydactyly type 1	HOXD13	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:295191	Zygodactyly type 3	HOXD13	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:295201	Congenital vertical talus, unilateral	HOXD10	1	NA	Rare genetic developmental defect during embryogenesis
Orphanet:295203	Congenital vertical talus, bilateral	HOXD10	1	NA	Rare genetic developmental defect during embryogenesis
Orphanet:295197	Synpolydactyly type 2	FBLN1	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:295239	Macrodactyly of fingers, unilateral	PIK3CA	1	NA	Rare genetic developmental defect during embryogenesis
Orphanet:295243	Macrodactyly of toes, unilateral	PIK3CA	1	NA	Rare genetic developmental defect during embryogenesis
Orphanet:300179	Kyphoscoliotic Ehlers-Danlos syndrome due to FKBP22 deficiency	FKBP14	1	Ehlers-Danlos syndrome, kyphoscoliotic and deafness type is a form of Ehlers-Danlos syndrome, characterized by severe generalized hypotonia at birth with severe early-onset kyphoscolosis along with joint hypermobility (without contractures) leading to recurrent dislocations, and sensorineural hearing impairment.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic systemic or rheumatologic disease
Orphanet:300319	Charcot-Marie-Tooth disease type 2P	LRSAM1	1	Charcot-Marie-Tooth disease type 2P is a rare, genetic, axonal hereditary motor and sensory neuropathy disorder characterized by adulthood-onset of slowly progressive, occasionally asymmetrical, distal muscle weakness and atrophy (predominantly in the lower limbs), pan-modal sensory loss, muscle cramping in extremities and/or trunk, pes cavus and absent or reduced deep tendon reflexes. Gait anomalies and variable autonomic disturbances, such as erectile dysfunction and urinary urgency, may be associated.	Rare genetic neurological disorder
Orphanet:300324	Persistent polyclonal B-cell lymphocytosis	CARD11	1	Persistent polyclonal B-cell lymphocytosis (PPBL) is a rare, generally benign, lymphoproliferative hematological disease characterized by: chronic, stable, persistent, polyclonal lymphocytosis of memory B-cell origin, the presence of binucleated lymphocytes in the peripheral blood, and a polyclonal increase in serum immunoglobulin M (IgM). Patients are most frequently asymptomatic or may present with mild splenomegaly.	
Orphanet:300313	Congenital cataract-hearing loss-severe developmental delay syndrome	SLC33A1	1	Congenital cataract-hearing loss-severe developmental delay syndrome is a rare, genetic, lethal, neurometabolic disease characterized by congenital cataracts, sensorineural hearing loss, severe psychomotor developmental delay, severe, generalized muscular hypotonia, and central nervous system abnormalities (incl. cerebellar and cerebral hypoplasia, hypomyelination, wide subarachnoid spaces), in the presence of low serum copper and ceruloplasmin. Nystagmus and seizures have also been reported.	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:300298	Severe congenital hypochromic anemia with ringed sideroblasts	STEAP3	1	STEAP3/TSAP6-related sideroblastic anemia is a very rare severe non-syndromic hypochromic anemia, which is characterized by transfusion-dependent hypochromic, poorly regenerative anemia, iron overload, resembling non-syndromic sideroblastic anemia (see this term) except for increased erythrocyte protoporphyrin levels.	Rare genetic hematologic disease
Orphanet:300284	Connective tissue disorder due to lysyl hydroxylase-3 deficiency	PLOD3	1	Connective tissue disorder due to lysyl hydroxylase-3 deficiency is a rare, genetic disease, caused by lack of lysyl hydrohylase 3 (LH3) activity, characterized by multiple tissue and organ involvement, including skeletal abnormalities (club foot, progressive scoliosis, osteopenia, pathologic fractures), ocular involvement (flat retinae, myopia, cataracts) and hair, nail and skin anomalies (coarse, abnormally distributed hair, skin blistering, reduced palmar creases, hypoplastic nails). Patients also present intrauterine growth retardation, facial dysmorphism (flat facial profile, low-set ears, shallow orbits, short and upturned nose, downturned corners of mouth) and joint flexion contractures. Growth and developmental delay, bilateral sensorineural deafness, friable diaphragm and later-onset spontaneous vascular ruptures are additional reported features.	Genetic otorhinolaryngologic disease;Rare genetic developmental defect during embryogenesis
Orphanet:300293	Transient infantile hypertriglyceridemia and hepatosteatosis	GPD1	1	Transient infantile hypertriglyceridemia and hepatosteatosis is a rare, genetic, hepatic disease characterized by massive hepatomegaly, moderate to severe, transient hypertriglyceridemia and hepatic steatosis (followed by fibrosis), manifesting in infancy with failure to thrive, vomiting, an enlarged abdomen and a fatty liver. Reduction or normalization of triglyceride serum levels occurs with advancing age.	Rare genetic hepatic disease
Orphanet:300382	Progeroid and marfanoid aspect-lipodystrophy syndrome	FBN1	1	Progeroid and marfanoid aspect-lipodystrophy syndrome is a rare systemic disease characterized by a neonatal progeroid appearance (not associated with other manifestations of premature aging) associated with facial dysmorphism (e.g. macrocephaly or arrested hydrocephaly, proptosis, downslanting palpebral fissures, retrognathia), generalized, extreme, congenital lack of subcutaneous fat tissue (except in the breast and iliac region) and incomplete signs of Marfan syndrome (mainly severe myopia, joint hyperextensibility and arachnodactyly). Metabolic disturbances are not associated.	
Orphanet:300345	Autosomal systemic lupus erythematosus	C1QA;C4A;DNASE1L3;PRKCD;DNASE1	5	Autosomal systemic lupus erythematosus is a rare, genetic, multisystemic, chronic autoimmune disease characterized by the presence of systemic lupus erythematosus symptoms in two or more members of a single family. Patients present a wide spectrum of clinical manifestations, including cutaneous (malar rash, photosensitivity), ocular (keratoconjunctivitis sicca, retinopathy), gastrointestinal (oral ulceration, abdominal pain), cardiac (atherosclerosis, chest pain), pulmonary (serositis, pleurisy), musculoskeletal (arthralgia, myalgia), renal (nephritis, hematuria), obstetrical (increased spontaneous abortions, neonatal lupus), constitutional (fatigue, loss of appetite) and neuropsychiatric (mood and cognitive disorders) involvement, among others.	Rare genetic systemic or rheumatologic disease
Orphanet:300359	PLCG2-associated antibody deficiency and immune dysregulation	PLCG2	1	PLCG2-associated antibody deficiency and immune dysregulation is a rare, hereditary, immune deficiency with skin involvement characterized by early-onset cold urticaria after generalized exposure to cold air or evaporative cooling and not after contact with cold objects. Additional immunologic abnormalities are often present - antibody deficiency, recurrent infections, autoimmune disease and symptomatic allergic disease.	Rare genetic immune disease;Rare genetic systemic or rheumatologic disease
Orphanet:300333	Nephrotic syndrome-deafness-pretibial epidermolysis bullosa syndrome	CD151	1	Nephrotic syndrome-deafness-pretibial epidermolysis bullosa syndrome is a rare, genetic, renal disease characterized by hereditary nephritis leading to nephrotic syndrome and end-stage renal failure associated with sensorineural hearing loss and pretibial skin blistering followed by atrophy. Other reported manifestations include bilateral lacrimal duct stenosis, dystrophic teeth and nails, bilateral cervical ribs, unilateral kidney, distal vaginal agenesis and anemia due to beta-thalassemia minor.	Genetic otorhinolaryngologic disease;Rare genetic renal disease
Orphanet:464724	Fever-associated acute infantile liver failure syndrome	NBAS	1	NA	Rare genetic hepatic disease
Orphanet:464738	Congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome	MED25	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:464760	Familial cavitary optic disc anomaly	MMP19	1	NA	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:464756	Familial gastric type 1 neuroendocrine tumor	ATP4A	1	NA	
Orphanet:465508	Symptomatic form of hemochromatosis type 1	HFE	1	Symptomatic form of hemochromatosis type 1 is a rare, hereditary hemochromatosis characterized by inappropriately regulated intestinal iron absorption which leads to excessive iron storage in various organs and manifests with a wide range of signs and symptoms, including abdominal pain, weakness, lethargy, weight loss, elevated serum aminotransferase levels, increase in skin pigmentation, and/or arthropathy in the metacarpophalangeal joints. Other commonly associated manifestations include hepatomegaly, cirrhosis, liver fibrosis, hepatocellular carcinoma, restrictive cardiomyopathy and/or diabetes mellitus.	Rare genetic hepatic disease;Rare inborn errors of metabolism
Orphanet:464282	Spastic paraplegia-severe developmental delay-epilepsy syndrome	HACE1	1	Spastic paraplegia-severe developmental delay-epilepsy syndrome is a rare, genetic, complex spastic paraplegia disorder characterized by an infantile-onset of psychomotor developmental delay with severe intellectual disability and poor speech acquisition, associated with seizures (mostly myoclonic), muscular hypotonia which may be noted at birth, and slowly progressive spasticity in the lower limbs leading to severe gait disturbances. Ocular abnormalities and incontinence are commonly associated. Other symptoms may include verbal dyspraxia, hypogenitalism, macrocephaly and sensorineural hearing loss, as well as dystonic movements and ataxia with upper limb involvement.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:464288	Short stature-brachydactyly-obesity-global developmental delay syndrome	PRMT7	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease;Rare genetic bone disease
Orphanet:464311	Intellectual disability syndrome due to a DYRK1A point mutation	DYRK1A	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:464366	NEK9-related lethal skeletal dysplasia	NEK9	1	NEK9-related lethal skeletal dysplasia is a rare, lethal, primary bone dysplasia characterized by fetal akinesia, multiple contractures, shortening of all long bones, short, broad ribs, narrow chest and thorax, pulmonary hypoplasia and a protruding abdomen. Short bowed femurs may also be associated.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:464336	BENTA disease	CARD11	1	NA	Rare genetic immune disease
Orphanet:464443	COG6-CGD	COG6	1	NA	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:464440	Primary dystonia, DYT27 type	COL6A3	1	NA	Rare genetic neurological disorder
Orphanet:464370	Neonatal alloimmune neutropenia	FCGR3B	1	NA	
Orphanet:456328	X-linked myotubular myopathy-abnormal genitalia syndrome	MAMLD1;MTM1	2	X-linked myotubular myopathy-abnormal genitalia syndrome is a rare chromosomal anomaly, partial deletion of the long arm of chromosome X, characterized by a combination of clinical manifestations of X-linked myotubular myopathy and a 46,XY disorder of sex development. Patients present with severe form of congenital myopathy and abnormal male genitalia.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease;Rare chromosomal anomaly
Orphanet:456333	Hereditary neuroendocrine tumor of small intestine	IPMK	1	NA	Inherited cancer-predisposing syndrome
Orphanet:456312	Infantile multisystem neurologic-endocrine-pancreatic disease	PTRH2	1	NA	Genetic otorhinolaryngologic disease;Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease;Rare genetic gastroenterological disease;Rare genetic neurological disorder
Orphanet:456318	Hereditary sensory neuropathy-deafness-dementia syndrome	DNMT1	1	NA	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder
Orphanet:454840	NTHL1-related attenuated familial adenomatous polyposis	NTHL1	1	NA	Rare genetic gastroenterological disease;Inherited cancer-predisposing syndrome;Rare genetic tumor
Orphanet:454821	Pleomorphic salivary gland adenoma	PLAG1;HMGA2	2	NA	
Orphanet:454745	Kuru	PRNP	1	A rare, acquired human prion disease characterized by rapidly progressive neurodegeneration, cerebellar symptoms (especially ataxia, but also tremor, dysarthria, and nystagmus) being the most prominent clinical feature, following an asymptomatic incubation period of up to several decades and a non-specific prodromal phase with headaches and arthralgia. Other neurological signs occurring in the course of the disease involve also the brain stem, mid-brain, hypothalamus, and cerebral cortex. Emotional changes include inappropriate euphoria and compulsive laughter, or depression and apprehension. The disease is invariably fatal within approximately one year.	
Orphanet:453533	Polyendocrine-polyneuropathy syndrome	DMXL2	1	NA	Rare genetic neurological disorder;Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility
Orphanet:453521	Autosomal recessive cerebellar ataxia due to CWF19L1 deficiency	CWF19L1	1	NA	Rare genetic neurological disorder
Orphanet:451612	Familial congenital nasolacrimal duct obstruction	IGSF3	1	A rare, genetic, otorhinolaryngological malformation characterized by congenital impatency of the nasolacrimal draingage system in various members of a family. Presentation is not specific and may include a uni- or bilateral medial canthal mass, dacryocystitis, nasal obstruction, periorbital cellulitis, and epiphora. Dacryocystocele and lacrimal puncta agenesis may be associated.	Rare genetic developmental defect during embryogenesis;Genetic otorhinolaryngologic disease;Rare genetic eye disease
Orphanet:453504	Neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-skeletal anomalies syndrome due to a point mutation	HNRNPK	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic cardiac disease;Rare genetic bone disease
Orphanet:453510	Congenital insensitivity to pain with severe intellectual disability	CLTCL1	1	NA	Rare genetic neurological disorder
Orphanet:449306	NA	MBL2	1	NA	NA
Orphanet:449291	Symptomatic form of fragile X syndrome in female carrier	FMR1	1	NA	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease
Orphanet:448372	OBSOLETE: X-linked acrogigantism due to Xq26 microduplication	GPR101	1	NA	NA
Orphanet:448264	Isolated focal non-epidermolytic palmoplantar keratoderma	TRPV3;KRT16	2	NA	Rare genetic skin disease
Orphanet:448251	Progressive autosomal recessive ataxia-deafness syndrome	SLC9A1	1	NA	Genetic otorhinolaryngologic disease
Orphanet:448267	Regressive spondylometaphyseal dysplasia	LBR	1	Regressive spondylometaphyseal dysplasia is a rare, primary bone dysplasia characterized by mild short stature, rhizomelic shortening of the arms and legs, bowing of long bones with widened and irregular metaphyses, thoracolumbar kyphosis, and metacarpal shortening. A marked improvement of the radiologic skeletal features is typical. Pelger-Huet anomaly (i.e. dumbbell shape bilobed nuclei of neutrophils) is a characteristic hematological feature of this disease.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:448010	CAD-CDG	CAD	1	 gene and characterized by epileptic encephalopathy, global developmental delay, normocytic anemia and anisopoikilocytosis. Loss of acquired skills in early childhood is present and natural disease course can be lethal in early childhood.	Rare inborn errors of metabolism
Orphanet:447997	Spastic tetraplegia-thin corpus callosum-progressive postnatal microcephaly syndrome	SLC1A4	1	NA	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:448242	Autosomal recessive brachyolmia	PAPSS2	1	Brachyolmia, recessive type is a form of brachyolmia (see this term), a group of rare genetic skeletal disorders, characterized by short-trunked short stature with platyspondyly and scoliosis. Corneal opacities and precocious calcification of the costal cartilage are rare syndromic components. Premature pubarche may occur.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:447977	Progressive scapulohumeroperoneal distal myopathy	ACTA1	1	NA	Rare genetic neurological disorder
Orphanet:447974	Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome	MYO18B	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic neurological disorder
Orphanet:447980	19p13.3 microduplication syndrome	NFIX	1	A rare, genetic, syndromic intellectual disability characterized by intrauterine growth retardation, microcephaly, hypotonia, motor and neurodevelopmental delay, speech delay, intellectual disability, and mild dysmorphic features.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare chromosomal anomaly
Orphanet:447954	Combined oxidative phosphorylation defect type 25	MARS2	1	Combined oxidative phosphorylation defect type 25 is a rare mitochondrial oxidative phosphorylation disorder with decreased respiratory complex I and IV enzyme activities, characterized by hypotonia, global developmental delay, neonatal onset of progressive pectus carinatum without other skeletal abnormalities, poor growth, sensorineural hearing loss, dysmorphic features and brain abnormalities such as cerebral atrophy, quadriventricular dilatation and thin corpus callosum posteriorly.	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:447964	Autosomal dominant Charcot-Marie-Tooth disease type 2V	NAGLU	1	A rare, axonal hereditary motor and sensory neuropathy characterized by adult onset of recurrent pain in legs with or without cramps, progressive loss of deep tendon reflexes and vibration sense, paresthesias in the feet and later in the hands. Patients often experience sleep disturbances and mild sensory ataxia.	Rare genetic neurological disorder
Orphanet:447961	Pigmentation defects-palmoplantar keratoderma-skin carcinoma syndrome	SASH1	1	NA	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:459353	C1 inhibitor deficiency	SERPING1	1	NA	Rare genetic immune disease;Serpinopathy
Orphanet:459033	Ataxia-oculomotor apraxia type 4	PNKP	1	NA	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:459051	Spondyloepiphyseal dysplasia, Stanescu type	COL2A1	1	NA	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:459061	Craniofacial dysplasia-short stature-ectodermal anomalies-intellectual disability syndrome	DPH1	1	A rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by craniofacial dysmorphism (including an abnormal skull shape, hypertelorism, downslanting palpebral fissures, epicanthal folds, low-set ears, depressed nasal bridge, micrognathia), short stature, ectodermal anomalies (such as sparse eyebrows, eyelashes, and scalp hair, hypolastic toenails), developmental delay, and intellectual disability. Additional features may include cerebral/cerebellar malformations and mild renal involvement.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:459056	Autosomal recessive spastic paraplegia type 75	MAG	1	Autosomal recessive spastic paraplegia type 75 is a rare, complex hereditary spastic paraplegia characterized by an early onset and slow progression of spastic paraplegia associated with cerebellar signs, nystagmus, peripheral neuropathy, extensor plantar responses and borderline to mild intellectual disability. Additional features of hypo- or areflexia, mild upper limb involvement and significant visual impairment (optic atrophy, vision loss, astigmatism) have been reported.	Rare genetic neurological disorder
Orphanet:459070	X-linked intellectual disability-cerebellar hypoplasia-spondylo-epiphyseal dysplasia syndrome	RPL10	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:458798	Spinocerebellar ataxia type 41	TRPC3	1	Spinocerebellar ataxia type 41 is a rare autosomal dominant cerebellar ataxia type III disorder characterized by adult-onset progressive imbalance and loss of coordination associated with an ataxic gait. Mild atrophy of the cerebellar vermis has been reported on brain magnetic resonance imaging.	Rare genetic neurological disorder
Orphanet:458803	Spinocerebellar ataxia type 42	CACNA1G	1	Spinocerebellar ataxia type 42 is a rare, autosomal dominant cerebellar ataxia characterized by pure and slowly progressive cerebellar signs combining gait instability, dysarthria, nystagmus, saccadic eye movements and diplopia. Less frequent clinical signs and symptoms include spasticity, hyperreflexia, decreased distal vibration sense, urinary urgency or incontinence and postural tremor.	Rare genetic neurological disorder
Orphanet:457485	Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome	MTOR	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:457265	Progressive myoclonic epilepsy type 9	LMNB2	1	A rare, genetic, neurological disorder characterized by childhood-onset severe myoclonic and tonic-clonic seizures and early-onset ataxia leading to severe gait disturbances associated with normal to slightly diminished cognition. Scoliosis, diffuse muscle atrophy and subcutaneous fat loss, as well as developmental delay, may be associated. Brain MRI may reveal complete agenesis of the corpus callosum, venticulomegaly, interhemispheric cysts, and simplified gyration (frontally).	Rare genetic neurological disorder
Orphanet:457279	Intellectual disability-macrocephaly-hypotonia-behavioral abnormalities syndrome	PPP2R5D	1	A rare, syndromic intellectual disability characterized by hypotonia, global developmental delay, limited or absent speech, intellectual disability, macrocephaly, mild dysmorphic features, seizures and autism spectrum disorder. Associated ophthalmologic, heart, skeletal and central nervous system anomalies have been reported.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:457260	X-linked intellectual disability-hypotonia-movement disorder syndrome	DDX3X	1	A rare, genetic, syndromic intellectual disability characterized by mild to severe intellectual disability associated with variable features, including hypotonia, dyskinesia, spasticity, wide-based gait, microcephaly, epilepsy and behavioral problems. MRI imaging may show a corpus callosum hypoplasia or ventricular enlargement. Other variable features, such as joint hyperlaxity, skin pigmentary abnormalities, and visual impairment, have also been reported.	Rare genetic neurological disorder
Orphanet:457240	X-linked intellectual disability-short stature-overweight syndrome	THOC2	1	X-linked intellectual disability-short stature-overweight syndrome is a multiple congenital anomalies syndrome characterized by borderline to severe intellectual disability, speech delay, short stature, elevated body mass index, a pattern of truncal obesity (reported in older males), and variable neurologic features (e.g. hypotonia, tremors, gait disturbances, behavioral problems, and seizure disorders). Less common manifestations include microcephaly, microorchidism and/or microphallus. Dysmorphic features have been reported in some patients but no consitent pattern has been noted.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:457246	Clear cell sarcoma of kidney	BCOR;YWHAE;NUTM2B;NUTM2E;TERT;IRX2	6	Clear cell sarcoma of kidney is a rare, primary, genetic renal tumor usually characterized by a unilateral, unicentric, morphologically diverse tumor that arises from the renal medulla and has a tendency for vascular invasion. Clinically it presents with a palpable abdominal mass, abdominal or flank pain, hematuria, anemia and/or fatigue. Metastatic spread to lymph nodes, bones, lungs, retroperitoneum, brain and liver is common at time of diagnosis and therefore bone pain, cough or neurological compromise may be associated. Metastasis to unusual sites, such as the scalp, neck, nasopharynx, axilla, orbits and epidural space, have been reported.	Rare genetic tumor
Orphanet:457395	Progressive spondyloepimetaphyseal dysplasia-short stature-short fourth metatarsals-intellectual disability syndrome	RSPRY1	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:457406	Multiple mitochondrial dysfunctions syndrome type 4	ISCA2	1	A rare, severe, genetic, neurometabolic disease characterized by infantile-onset of progressive neurodevelopmental regression, optic atrophy with nystagmus and diffuse white matter disease. Affected individuals usually have central hypotonia that progresses to limb spasticity and hyperreflexia, eventually resulting in a vegetative state. Recurrent chest infections are frequently associated and seizures (usually generalized tonic-clonic) may occasionally be observed. Brain magnetic resonance imaging shows diffuse bilateral symmetric abnormalities in the cerebral periventricular white matter, with variable lesions in other areas but sparing the basal ganglia.	Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:457375	ITPA-related lethal infantile neurological disorder with cataract and cardiac involvement	ITPA	1	A rare, genetic, neurometabolic disease characterized by early onset encephalopathy with progressive microcephaly, severe global development delay, seizures, hypotonia, feeding difficulties, variable cardiac abnormalities, and cataracts. Brain MRI shows distinct pattern with high T2 signal and restricted diffusion in the posterior limb of the internal capsule in combination with delayed myelination and progressive cerebral atrophy. The disease is typically fatal.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:457378	Complex lethal osteochondrodysplasia	TAPT1	1	A rare, genetic, primary bone dysplasia with decreased bone density characterized by fetal lethality, severe hypomineralization of the entire skeleton, barrel shaped thorax with short ribs, multiple intrauterine fractures of ribs and long bones, ascites, pleural effusion, and ventriculomegaly. Variable congenital developmental anomalies affecting the brain, lungs, and kidneys have also been associated.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:457359	Megalencephaly-severe kyphoscoliosis-overgrowth syndrome	HERC1	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:457284	Microcephaly-corpus callosum hypoplasia-intellectual disability-facial dysmorphism syndrome	PPP2R1A	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:457351	Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome	SPATA5	1	NA	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:457185	Neonatal encephalomyopathy-cardiomyopathy-respiratory distress syndrome	COQ4	1	NA	Rare genetic cardiac disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:457088	Predisposition to invasive fungal disease due to CARD9 deficiency	CARD9	1	A rare, genetic primary immunodeficiency characterized by increased susceptibility to fungal infections, typically manifesting as recurrent, chronic mucocutaneous candidiasis, systemic candidiasis with meningoencephalitis, and deep dermatophystosis with dermatophytes invading skin, hair, nails, lymph nodes, and brain, resulting in erythematosquamous lesions, nodular subcutaneous or ulcerative infiltrations, severe onychomycosis, and lymphadenopathy.	Rare genetic immune disease
Orphanet:457223	Syndromic sensorineural deafness due to combined oxidative phosphorylation defect	MRPS7	1	NA	Genetic otorhinolaryngologic disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:457212	Progressive essential tremor-speech impairment-facial dysmorphism-intellectual disability-abnormal behavior syndrome	SLC6A17	1	NA	Rare genetic neurological disorder
Orphanet:457193	Autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome	KAT6A	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic cardiac disease;Rare genetic bone disease
Orphanet:456369	Polyglucosan body myopathy type 2	GYG1	1	NA	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:457050	Autosomal dominant mitochondrial myopathy with exercise intolerance	CHCHD10	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:317	Erythrokeratodermia variabilis	GJA1;GJB4;GJB3;KDSR	4	NA	Rare genetic eye disease;Rare genetic skin disease
Orphanet:629	Short stature due to growth hormone qualitative anomaly	GH1	1	 gene (17q22-q24) that result in structural GH anomalies and a biologically inactive molecule. Transmission is autosomal recessive.	Rare genetic endocrine disease
Orphanet:632	Short stature due to isolated growth hormone deficiency with X-linked hypogammaglobulinemia	BTK;ELF4	2	NA	Rare genetic immune disease
Orphanet:248	Autosomal recessive hypohidrotic ectodermal dysplasia	EDAR;EDARADD;WNT10A	3	NA	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:1810	Autosomal dominant hypohidrotic ectodermal dysplasia	EDAR;EDARADD;TRAF6;KDF1	4	NA	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:3437	Vogt-Koyanagi-Harada disease	FAS;PTPN22	2	Vogt-Koyanagi-Harada disease is a bilateral, chronic, diffuse granulomatous panuveitis typically characterized by serous retinal detachment and frequently associated with neurological (meningitis), auditory, and dermatological alterations.	
Orphanet:2032	Idiopathic pulmonary fibrosis	SFTPA1;DSP;TERT;TERC;MUC5B;SFTPA2;RTEL1;FAM13A;STN1;ATP11A;DPP9;PARN;SFTPC;ABCA3	14	Idiopathic pulmonary fibrosis (IPF) is a nonneoplastic pulmonary disease that is characterized by the formation of scar tissue within the lungs in the absence of any known cause.	
Orphanet:198	Occipital horn syndrome	ATP7A	1	Occipital horn syndrome (OHS) is a mild form of Menkes disease (MD, see this term), a syndrome characterized by progressive neurodegeneration and connective tissue disorders due to a copper transport defect.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic skin disease
Orphanet:891	Familial exudative vitreoretinopathy	CTNNB1;FZD4;LRP5;NDP;TSPAN12;ZNF408	6	Familial exudative vitreoretinopathy (FEVR) is a rare hereditary vitreoretinal disorder characterized by abnormal or incomplete vascularization of the peripheral retina leading to variable clinical manifestations ranging from no effects to minor anomalies, or even retinal detachment with blindness.	Rare genetic eye disease;Rare genetic neurological disorder
Orphanet:225	Maternally-inherited diabetes and deafness	MT-TE;MT-TL1;MT-TK	3	Maternally inherited diabetes and deafness (MIDD) is a mitochondrial disorder characterized by maternally transmitted diabetes and sensorineural deafness.	Genetic otorhinolaryngologic disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic eye disease;Rare genetic endocrine disease
Orphanet:466688	Severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome	FRMD4A	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:466650	Exercise-induced malignant hyperthermia	RYR1	1	NA	
Orphanet:466962	SMARCA4-deficient sarcoma of thorax	SMARCA4	1	NA	
Orphanet:466950	Facial dysmorphism-developmental delay-behavioral abnormalities syndrome due to WAC point mutation	WAC	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:466926	Seizures-scoliosis-macrocephaly syndrome	EXT2	1	Seizures-scoliosis-macrocephaly syndrome is a rare, genetic neurometabolic disorder characterized by seizures, macrocephaly, delayed motor milestones, moderate intellectual disability, scoliosis with no exostoses, muscular hypotonia present since birth, as well as renal dysfunction. Coarse facial features (including hypertelorism and long hypoplastic philtrum) and bilateral cryptorchidism (in males) are also commonly reported. Additional manifestations include abnormal gastrointestinal motility (resulting in constipation, diarrhea, gastroesophageal reflux and dysphagia), gait disturbances, strabismus and ventricular septal defects.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:466934	VPS11-related autosomal recessive hypomyelinating leukodystrophy	VPS11	1	NA	Rare genetic neurological disorder
Orphanet:466921	Childhood-onset progressive contractures-limb-girdle weakness-muscle dystrophy syndrome	TTN	1	NA	Rare genetic neurological disorder
Orphanet:466806	Autosomal dominant thrombocytopenia with platelet secretion defect	SLFN14	1	NA	Rare genetic hematologic disease
Orphanet:466801	Autosomal recessive limb-girdle muscular dystrophy type 2W	LIMS2	1	A subtype of autosomal recessive limb girdle muscular dystrophy characterized by childhood onset of severe, progressive, proximal skeletal muscle weakness and atrophy of the upper and lower limbs with later involvement of distal muscles and development of severe quadraparesis, calf hypertrophy, triangular tongue, and dilated cardiomyopathy. Skeletal muscles undergo diffuse, bilateral, symmetric and severe atrophy with fat infiltration.	Rare genetic cardiac disease;Rare genetic neurological disorder
Orphanet:466794	Acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome	SCYL1	1	NA	Rare genetic neurological disorder;Rare genetic hepatic disease
Orphanet:466791	Macrocephaly-intellectual disability-left ventricular non compaction syndrome	NONO	1	Macrocephaly-intellectual disability-left ventricular non compaction syndrome is a rare, genetic, syndromic intellectual disability characterized by motor and cognitive developmental delay with language impairment, macrocephaly, hypotonia, dysmorphic facial features (including long face, slanting palpebral fissures and prominent, flattened nose) and left ventricular noncompaction cardiomyopathy. Patients also present skeletal abnormalities (e.g. scoliosis, finger clinodactyly, pes planus), slender build and shy behavior. Strabismus and various neurological signs (including ataxia, tremor and hyperreflexia) may be associated, as well as epilepsy, autism and MRI findings showing a small cerebellum and abnormalities of the corpus callosum. A phenotypic variant with no cardiac involvement has been reported.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:466784	Neonatal severe cardiopulmonary failure due to mitochondrial methylation defect	SLC25A26	1	NA	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:466775	Autosomal recessive Charcot-Marie-Tooth disease type 2X	SPG11	1	NA	Rare genetic neurological disorder
Orphanet:466768	Autosomal dominant Charcot-Marie-Tooth disease type 2Z	MORC2	1	NA	Rare genetic neurological disorder
Orphanet:466729	Familial patent arterial duct	TFAP2B;PRDM6	2	Familial patent arterial duct is a rare, genetic, non-syndromic, congenital anomaly of the great arteries characterized by the presence of an isolated patent arterial duct (PDA) (i.e. failure of closure of ductus arteriosis after birth) in several members of the same family. Clinical presentation is similar to the sporadic form and may range from neonatal-onset tachypnea, diaphoresis and failure to thrive to adult-onset atrial arrhythmia, signs and symptoms of heart failure and cyanosis limited to the lower extremities.	Rare genetic developmental defect during embryogenesis
Orphanet:466722	Autosomal recessive spastic paraplegia type 77	FARS2	1	Autosomal recessive spastic paraplegia type 77 is a rare, pure or complex hereditary spastic paraplegia characterized by an infancy to childhood onset of slowly progressive lower limb spasticity, delayed motor milestones, gait disturbances, hyperreflexia and various muscle abnormalities, including weakness, hypotonia, intention tremor and amyotrophy. Ocular abnormalities (e.g. strabismus, ptosis) and other neurological abnormalities, such as dysarthria, seizures and extensor plantar responses, may also be associated.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:466718	Martinique crinkled retinal pigment epitheliopathy	MAPKAPK3	1	NA	Rare genetic eye disease
Orphanet:466703	TMEM199-CDG	TMEM199	1	NA	Rare inborn errors of metabolism;Rare genetic endocrine disease
Orphanet:465824	Fetal encasement syndrome	CHUK	1	Fetal encasement syndrome is a rare, lethal developmental defect during embryogenesis characterized by severe fetal malformations, including craniofacial dysmorphism (abnormal cyst in the cranial region, hypoplastic eyeballs, two orifices in the nasal region separated by a nasal septum, abnormal orifice replacing the mouth), omphalocele and immotile, hypoplastic limbs encased under an abnormal, transparent, membrane-like skin. Additional features include absence of adnexal structures of the skin on the outer aspect of the limbs, as well as underdeveloped skeletal muscles and bones. Association with tetralogy of Fallot, horse-shoe kidneys and diaphragm and lung lobulation defects is reported.	Rare genetic developmental defect during embryogenesis
Orphanet:466026	Class I glucose-6-phosphate dehydrogenase deficiency	G6PD	1	NA	Rare genetic hematologic disease
Orphanet:468620	Intellectual disability-epilepsy-extrapyramidal syndrome	DEAF1	1	NA	Rare genetic neurological disorder
Orphanet:468631	Microcephalic primordial dwarfism due to RTTN deficiency	RTTN	1	Microcephalic primordial dwarfism due to RTTN deficiency is a rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by primary microcephaly, profound short stature, moderate to severe intellectual disability, global developmental delay, craniofacial dysmorphism (e.g. sloping forehead, high and broad nasal bridge) and variable brain malformations, including simplified gyration, pachygyria, polymicrogyria, reduced sulcation, dysgenesis of corpus callosum and deformed ventricles. Renal anomalies, bilateral hearing loss, multiple joint contractures, severe failure to thrive and a sacral lesion cephalad to the gluteal crease have also been reported.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:467166	Tubulinopathy-associated dysgyria	TUBA1A;TUBB2B;TUBB3	3	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:467176	Severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndrome	CCDC174	1	Severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndrome is a rare, genetic, non-dystrophic congenital myopathy disorder characterized by a neonatal-onset of severe generalized hypotonia associated with mild psychomotor delay, congenital strabismus with abducens nerve palsy, and atrial and/or ventricular septal defects. Cryptorchidism is commonly reported in male patients and muscle biopsy typically reveals increased variability in muscle fiber size.	Rare genetic eye disease;Rare genetic cardiac disease;Rare genetic neurological disorder
Orphanet:468635	Cryptogenic multifocal ulcerous stenosing enteritis	PLA2G4A	1	NA	Rare genetic gastroenterological disease
Orphanet:468641	Chronic enteropathy associated with SLCO2A1 gene	SLCO2A1	1	NA	Rare genetic gastroenterological disease
Orphanet:468661	Autosomal recessive spastic paraplegia type 74	IBA57	1	Autosomal recessive spastic paraplegia type 74 is a rare, genetic, spastic paraplegia-optic atrophy-neuropathy-related (SPOAN-like) disorder characterized by childhood onset of mild to moderate spastic paraparesis which manifests with gait impairment that very slowly progresses into late adulthood, hyperactive patellar reflex and bilateral extensor plantar response, in association with optic atrophy and typical symptoms of peripheral neuropathy, including reduced or absent ankle reflexes, lower limb atrophy and distal sensory impairment. Reduced visual acuity and pes cavus are frequently reported.	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:468666	Isolated generalized anhidrosis with normal sweat glands	ITPR2	1	NA	Rare genetic skin disease
Orphanet:468678	Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome	POGZ	1	Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome is a rare, genetic, syndromic intellecutal disability disorder characterized by craniofacial dysmorphism (microcephaly, hypotonic facies, strabismus, long and flat malar region, posteriorly rotated ears, flat nasal bridge with broad nasal tip, short philtrum, thin vermillion border, open mouth with down-turned corners, high arched palate, pointed chin), global developmental delay, intellectual disability and variable neurobehavioral abnormalities (autism spectrum disorder, aggressivness, self injury). Additional features include vision abnormalities and variable sensorineural hearing loss, as well as short stature, hypotonia and gastrointestinal manifestations (e.g. poor feeding, gastroesophageal reflux, constipation).	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:468684	CCDC115-CDG	CCDC115	1	NA	Rare inborn errors of metabolism;Rare genetic endocrine disease
Orphanet:468672	Colobomatous macrophthalmia-microcornea syndrome	CRIM1	1	NA	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:468726	Severe primary trimethylaminuria	FMO3	1	NA	Rare inborn errors of metabolism
Orphanet:468699	SLC39A8-CDG	SLC39A8	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:468717	Rhizomelic chondrodysplasia punctata type 5	PEX5	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:401785	Autosomal recessive spastic paraplegia type 62	ERLIN1	1	A pure or complex form of hereditary spastic paraplegia characterized by an onset in the first decade of life of spastic paraperesis (more prominent in lower than upper extremities) and unsteady gait, as well as increased deep tendon reflexes, amyotrophy, cerebellar ataxia, and flexion contractures of the knees, in some.	Rare genetic neurological disorder
Orphanet:401780	Autosomal recessive spastic paraplegia type 61	ARL6IP1	1	 gene (16p12-p11.2) encoding the ADP-ribosylation factor-like protein 6-interacting protein 1.	Rare genetic neurological disorder
Orphanet:401800	Autosomal recessive spastic paraplegia type 60	WDR48	1	Autosomal recessive spastic paraplegia type 60 is a rare, complex hereditary spastic paraplegia disorder characterized by infantile onset of progressive lower limb spasticity, inability to walk, hypertonia and impaired vibration sense at ankles, with complicating signs including sensory impairment, nystagmus, motor axonal neuropathy and mild intellectual disability.	Rare genetic neurological disorder
Orphanet:401795	Autosomal recessive spastic paraplegia type 59	USP8	1	Autosomal recessive spastic paraplegia type 59 is a very rare, complex hereditary spastic paraplegia characterized by an early onset of progressive lower limb spasticity, tip-toe walking, scissor gait, hyperreflexia and clonus that may be associated with borderline intellectual disability. Nystagmus and pes equinovarus have also been reported.	Rare genetic neurological disorder
Orphanet:401768	Proximal myopathy with extrapyramidal signs	MICU1	1	Proximal myopathy with extrapyramidal signs is a rare, hereditary non-dystrophic myopathy characterized by proximal muscle weakness, delayed motor development, learning difficulties, and progressive extrapyramidal motor signs including chorea, dystonia and tremor. Variable additional features have been reported - ataxia, microcephaly, ophthalmoplegia, ptosis, and optic atrophy.	Rare genetic neurological disorder
Orphanet:401764	Pancytopenia-developmental delay syndrome	ERCC6L2	1	Pancytopenia-developmental delay syndrome is a rare, genetic, hematologic disorder characterized by progressive trilineage bone marrow failure (with hypocellularity), developmental delay with learning disabilities, and microcephaly. Mild facial dysmorphism and hypotonia have also been reported.	Rare genetic hematologic disease
Orphanet:401777	Optic atrophy-intellectual disability syndrome	NR2F1	1	Optic atrophy-intellectual disability syndrome is a rare, hereditary, syndromic intellectual disability characterized by developmental delay, intellectual disability, and significant visual impairment due to optic nerve atrophy, optic nerve hypoplasia or cerebral visual impairment. Other common clinical signs and symptoms are hypotonia, oromotor dysfunction, seizures, autism spectrum disorder, and repetitive behaviors. Dysmorphic facial features are variable and nonspecific.	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:401830	Autosomal recessive spastic paraplegia type 69	RAB3GAP2	1	Autosomal recessive spastic paraplegia type 69 is a rare, complex hereditary spastic paraplegia disorder characterized by infantile onset of progressive lower limb spasticity, global developmental delay, hyperreflexia, clonus and extensor plantar reflexes, associated with dysarthria, intellectual disability, cataracts and hearing impairment.	Rare genetic neurological disorder
Orphanet:401835	Autosomal recessive spastic paraplegia type 70	MARS	1	Autosomal recessive spastic paraplegia type 70 is a very rare, complex subtype of hereditary spastic paraplegia that presents in infancy with delayed motor development (i.e. crawling, walking) and is characterized by lower limb spasticity, increased deep tendon reflexes, extensor plantar responses, impaired vibratory sensation at ankles, amyotrophy and borderline intellectual disability. Additional signs may include gait disturbances, Achilles tendon contractures, scoliosis and cerebellar abnormalities.	Rare genetic neurological disorder
Orphanet:401840	Autosomal recessive spastic paraplegia type 71	ZFR	1	Autosomal recessive spastic paraplegia type 71 is a rare, genetic, pure hereditary spastic paraplegia disorder characterized by infancy onset of crural spastic paraperesis with scissors gait, extensor plantar response, and increased tendon reflexes. Neuroimaging reveals a thin corpus callosum and electromyography and nerve conduction velocity studies are normal.	Rare genetic neurological disorder
Orphanet:401805	Autosomal recessive spastic paraplegia type 63	AMPD2	1	 gene (1p13.3) encoding AMP deaminase 2.	Rare genetic neurological disorder
Orphanet:401810	Autosomal recessive spastic paraplegia type 64	ENTPD1	1	 gene (10q24.1), encoding ectonucleoside triphosphate diphosphohydrolase 1.	Rare genetic neurological disorder
Orphanet:401815	Autosomal recessive spastic paraplegia type 66	ARSI	1	Autosomal recessive spastic paraplegia type 66 is a rare, complex hereditary spastic paraplegia disorder characterized by infantile onset of progressive lower limb spasticity, severe gait disturbances leading to a non-ambulatory state, absent deep tendon reflexes and amyotrophy. Additional signs include severe sensorimotor neuropathy, pes equinovarus and mild intellectual disability. Cerebellar and corpus callosum hypoplasia, as well as colpocephaly, are observed on neuroimaging.	Rare genetic neurological disorder
Orphanet:401820	Autosomal recessive spastic paraplegia type 67	PGAP1	1	Autosomal recessive spastic paraplegia type 67 is an extremely rare, complex hereditary spastic paraplegia characterized by an infancy or childhood onset of global developmental delay and progressive spasticity with tremor in the distal limbs, increased deep tendon reflexes and extensor plantar responses, which may be associated with mild intellectual disability. Additional features include muscle wasting and cerebellar abnormalities.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:401866	Childhood-onset spasticity with hyperglycinemia	GLRX5	1	Childhood-onset spasticity with hyperglycinemia is a rare neurometabolic disease characterized by a childhood onset of progressive spastic ataxia associated with gait disturbances, hyperreflexia, extensor plantar responses and non-ketotic hyperglycinemia typically revealed by biochemical analysis. Additional signs of upper extremity spasticity, dysarthria, learning difficulties, poor concentration, nystagmus, optic atrophy and reduced visual acuity may also be associated.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:401869	Multiple mitochondrial dysfunctions syndrome type 1	NFU1	1	NA	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:401874	Multiple mitochondrial dysfunctions syndrome type 2	BOLA3	1	NA	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:401849	Autosomal spastic paraplegia type 72	REEP2	1	Autosomal spastic paraplegia type 72 is a rare, genetic, pure hereditary spastic paraplegia disorder characterized by early childhood onset of slowly progressive crural spastic paraparesis presenting with spastic gait, mild stiffness at rest, hyperreflexia (in lower limbs), extensor plantar responses and, in some, mild postural tremor, pes cavus, sphincter disturbances and sensory loss at ankles.	Rare genetic neurological disorder
Orphanet:401859	Lipoic acid synthetase deficiency	LIAS	1	Lipoic acid synthetase deficiency is a rare neurometabolic disease characterized by a neonatal onset of seizures (often intractable), muscular hypotonia, feeding difficulties (poor sucking and/or swallowing) and mild to severe psychomotor delay, associated with nonketotic hyperglycinemia typically revealed by biochemical analysis. Respiratory problems (apnea, acute respiratory acidosis), lethargy, hearing loss, microcephaly and spasticity with pyramidal signs may also be associated.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:401862	Lipoyl transferase 1 deficiency	LIPT1	1	Lipoyl transferase 1 deficiency is a very rare inborn error of metabolism disorder, with a highly variable phenotype, typically characterized by neonatal to infancy-onset of seizures, psychomotor delay, and abnormal muscle tone that may include hypo- and/or hypertonia, resulting in generalized weakness, dystonic movements, and/or progressive respiratory distress, associated with severe lactic acidosis and elevated lactate, ketoglutarate and 2-oxoacids in urine. Additional manifestations may include dehydration, vomiting, signs of liver dysfunction, extrapyramidal signs, spastic tetraparesis, brisk deep tendon reflexes, speech impairment, swallowing difficulties, and pulmonary hypertension.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:401920	Fibrolamellar hepatocellular carcinoma	DNAJB1;PRKACA	2	NA	
Orphanet:401911	AXIN2-related attenuated familial adenomatous polyposis	AXIN2	1	NA	Rare genetic gastroenterological disease;Inherited cancer-predisposing syndrome;Rare genetic tumor
Orphanet:401901	Huntington disease-like syndrome due to C9ORF72 expansions	C9ORF72	1	Huntington disease-like syndrome due to C9ORF72 expansions is a rare, genetic neurodegenerative disease characterized by movement disorders, including dystonia, chorea, myoclonus, tremor and rigidity. Associated features are also cognitive and memory impairment, early psychiatric disturbances and behavioral problems.	Rare genetic neurological disorder
Orphanet:401959	Partial corpus callosum agenesis-cerebellar vermis hypoplasia with posterior fossa cysts syndrome	KPNA7	1	Partial corpus callosum agenesis-cerebellar vermis hypoplasia with posterior fossa cysts syndrome is a rare, hereditary, cerebral malformation with epilepsy syndrome characterized by severe global developmental delay with no ability to walk and no verbal language, intractable epilepsy, partial agenesis of the corpus callosum and cerebellar vermis hypoplasia with posterior fossa cysts.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:401948	Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency	CA5A	1	A rare, hereditary inborn error of metabolism characterized by an acute onset of encephalopathy in infancy or early childhood. Apart from these episodic acute events, the disorder shows a relatively benign course. Multiple metabolic abnormalities are present, including metabolic acidosis, respiratory alkalosis, hypoglycemia, increased serum lactate and alanine.	Rare inborn errors of metabolism
Orphanet:401945	Moyamoya disease with early-onset achalasia	GUCY1A1	1	Moyamoya disease with early-onset achalasia is an exceedingly rare autosomal recessive neurological disorder reported only in a few families so far. It is characterized by the association of early onset achalasia (manifesting in infancy) with severe intracranial angiopathy that is consistent with moyamoya angiopathy in most cases (moyamoya disease; see this term). Other variable associated manifestations include hypertension, Raynaud phenomenon, and livedo reticularis.	Rare genetic gastroenterological disease;Rare genetic neurological disorder
Orphanet:401986	1p31p32 microdeletion syndrome	NFIA	1	1p31p32 microdeletion syndrome is a rare chromosomal anomaly syndrome, resulting from the partial deletion of the short arm of chromosome 1, characterized by developmental delay, corpus callosum agenesis/hypoplasia and craniofacial dysmorphism, such as macrocephaly (caused by hydrocephalus or ventriculomegaly), low-set ears, anteverted nostrils and micrognathia. Urinary tract defects (e.g. vesicoureteral reflux, urinary incontinence) are also frequently associated. Other reported variable manifestations include hypotonia, tethered spinal cord, Chiari type I malformation and seizures.	Rare genetic developmental defect during embryogenesis;Rare chromosomal anomaly
Orphanet:401979	Autosomal recessive spondylometaphyseal dysplasia, Mégarbané type	PAM16	1	Autosomal recessive spondylometaphyseal dysplasia, Mégarbané type is a rare, primary bone dysplasia characterized by intrauterine growth retardation, pre- and postnatal disproportionate short stature with short, rhizomelic limbs, facial dysmorphism, a short neck and small thorax. Hypotonia, cardiomegaly and global developmetal delay have also been associated. Several radiographic findings have been reported, including ribs with cupped ends, platyspondyly, square iliac bones, horizontal and trident acetabula, hypoplastic ischia, and delayed epiphyseal ossification.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:401973	MEND syndrome	EBP	1	MEND syndrome is a rare, genetic, syndromic, sterol biosynthesis disorder affecting males characterized by skin manifestations, including collodion membrane, ichthyosis, and patchy hypopigmentary lesions, associated with severe neurological involvement (e.g. intellectual disability, delayed psychomotor development, seizures, hydrocephalus, cerebellar/corpus callosum hypoplasia, Dandy-Walker malformation, hypotonia) and craniofacial dysmorphism (large anterior fontanelle, telecanthus, hypertelorism, microphthalmia, prominent nasal bridge, low-set ears, micrognathia, cleft palate). 2,3 toe syndactyly, polydactyly, and kyphosis, as well as ophthalmic, cardiac and urogenital anomalies may also be associated.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:401964	Autosomal dominant Charcot-Marie-Tooth disease type 2 with giant axons	DCAF8	1	A rare subtype of axonal hereditary motor and sensory neuropathy characterized by distal muscle weakness and atrophy (principally of peroneal muscles) associated with distal sensory loss (tactile, vibration), pes cavus present since infancy or childhood, and axonal swelling with neurofilament accumulation on nerve biopsy. Other features may include hand muscle involvement, hypo/arreflexia, gait disturbances, muscle cramps, toe abnormalities and mild cardiomyopathy.	Rare genetic neurological disorder
Orphanet:402003	Autosomal dominant focal non-epidermolytic palmoplantar keratoderma with plantar blistering	KRT6C	1	A rare, genetic, isolated, focal palmoplantar keratoderma disease characterized by focal thickening of the skin of the soles, and often of the palms, associated with minimal or no nail involvement. Patients frequently present non-epidermolytic painful plantar blistering and, occasionally, subtle oral leukokeratosis or plantar hyperhidrosis.	Rare genetic skin disease
Orphanet:401996	Karyomegalic interstitial nephritis	FAN1	1	Karyomegalic interstitial nephritis is a rare, genetic renal disease characterized by slowly progressive, chronic, tubulointerstitial nephritis, leading to end-stage renal disease before the age of 50 years, manifesting with mild proteinuria, glucosuria and, occasionally, urinary sediment abnormalities (mainly hematuria). Mild extrarenal manifestations, such as recurrent upper respiratory tract infections and abnormal liver function tests, may be associated. Renal biopsy reveals severe, chronic, interstitial fibrosis and tubular changes, as well as hallmark karyomegalic tubular epithelial cells which line the proximal and distal tubules and have enlarged, hyperchromatic nuclei.	Rare genetic renal disease
Orphanet:402017	Acute myeloid leukemia with t(9;11)(p22;q23)	KMT2A;MLLT3	2	A tumor of hematopoietic and lymphoid tissues characterized by the most common AML-causing MLL translocation, resulting in the MLL-MLLT3-fusion protein. It can occur either as a primary neoplasm or secondary to previous chemo-/radiation therapy. Clinical manifestations result from accumulation of malignant myeloid cells within the bone marrow, peripheral blood and other organs and include leukocytosis, anemia, thrombocytopenia, fever, bone pain, fatigue, pallor, easy bruising and frequent bleeding.	
Orphanet:402020	Acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2)	MECOM;RPN1	2	A subtype of acute myeloid leukemia with recurrent genetic abnormalities characterized by clonal proliferation of myeloid blasts in the bone marrow, blood and, rarely, other tissues. Bone marrow typically shows small, hypolobated megakaryocytes and multilineage dyslplasia. Patients typically present with leukocytosis, anemia, variable platelet counts and a variety of nonspecific symptoms related to ineffective hematopoesis (fatigue, bleeding, bruising, recurrent infections, bone pain) and/or extramedullary site involvement (gingivitis, splenomegaly). High resistance to conventional chemotherapy is reported.	
Orphanet:402014	Acute myeloid leukemia with t(6;9)(p23;q34)	NUP214;DEK	2	A rare subtype of acute myeloid leukemia with recurrent genetic abnormalities characterized by clonal proliferation of poorly differentiated myeloid blasts in the bone marrow, blood, or other tissues in patients who present the t(6;9)(p23;q34) translocation. Frequently associated with multilineage bone marrow dysplasia, it usually presents with anemia, thrombocytopenia (often pancytopenia), and other nonspecific symptoms related to ineffective hematopoesis (fatigue, bleeding and bruising, recurrent infections, bone pain) and/or extramedullary site involvement (gingivitis, splenomegaly). Basophilia, as well as poor response to chemotherapy, has been reported.	
Orphanet:402023	Megakaryoblastic acute myeloid leukemia with t(1;22)(p13;q13)	RBM15;MKL1	2	Megakaryoblastic acute myeloid leukemia with t(1;22)(p13;q13) is a rare subtype of acute myeloid leukemia with recurrent cytogenetic abnormalities characterized by clonal proliferation of myeloid blasts with predominantly megakaryoblastic differentiation in the bone marrow and blood, often with extensive infiltration of the abdominal organs. It occurs typically in infants and usually presents with hepatosplenomegaly, anemia, thrombocytopenia and nonspecific symptoms related to ineffective hematopoiesis (fatigue, bleeding and bruising, recurrent infections). Myelofibrosis and fibrosis of other infiltrated organs is also characteristic of this disease.	
Orphanet:402026	Acute myeloid leukemia with NPM1 somatic mutations	NPM1	1	 gene in the bone marrow, blood and other tissues. It is associated with multilineage dysplasia, involving the myeloid, monocytic, erythroid, and megakaryocytic cell lineages.	
Orphanet:402082	Progressive myoclonic epilepsy type 5	PRICKLE2;POLG	2	A rare, genetic neurological disorder characterized by early-onset progressive ataxia associated with myoclonic seizures, generalized tonic-clonic seizures (which are often sleep-related), and normal to mild intellectual disability. Dysarthria, upward gaze palsy, sensory neuropathy, developmental delay and autistic disorder have also been associated.	Rare genetic neurological disorder
Orphanet:402364	Infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly	MED17	1	Infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly is a rare, central nervous system malformation syndrome characterized by progressive microcephaly with profound motor delay and intellectual disability, associated with hypertonia, spasticity, clonus, and seizures, with brain imaging revealing severe cerebral and cerebellar atrophy, and poor myelination.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:402041	Autosomal recessive distal renal tubular acidosis	FOXI1;ATP6V0A4;ATP6V1B1	3	An inherited form of distal renal tubular acidosis (dRTA) characterized by hypokalemic hyperchloremic metabolic acidosis. Deafness often occurs either early or later on in life but may be absent or never be diagnosed.	Genetic otorhinolaryngologic disease;Rare genetic renal disease
Orphanet:402075	Familial bicuspid aortic valve	NKX2-5;GATA5;NOTCH1;SMAD6	4	Familial bicuspid aortic valve is a rare, genetic, aortic malformation defined as a presence of abnormal two-leaflet aortic valve in at least 2 first-degree relatives. It is frequently asymptomatic or may be associated with progressive aortic valve disease (aortic regurgitation and/or aortic stenosis, typically due to valve calcification) and a concomitant aortopathy (i.e. aortic dilation, aortic aneurysm and/or dissection).	Rare genetic vascular disease;Rare genetic developmental defect during embryogenesis
Orphanet:806	Scott syndrome	ANO6	1	Scott syndrome is an extremely rare congenital hemorrhagic disorder characterized by hemorrhagic episodes due to impaired platelet coagulant activity.	Rare genetic hematologic disease
Orphanet:404473	Severe intellectual disability-progressive spastic diplegia syndrome	CTNNB1	1	Severe intellectual disability-progressive spastic diplegia syndrome is a rare, genetic, syndromic intellectual disability disorder characterized by intellectual disability, significant motor delay, severe speech impairment, early-onset truncal hypotonia with progressive distal hypertonia/spasticity, microcephaly, and behavioral anomalies (autistic features, aggression or auto-aggressive behavior, sleep disturbances). Variable facial dysmorphism includes broad nasal tip with small alae nasi, long and/or flat philtrum, thin upper lip vermillion. Visual impairment (strabismus, hyperopia, myopia) is commonly associated.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:404463	Multisystemic smooth muscle dysfunction syndrome	ACTA2	1	Multisystemic smooth muscle dysfunction syndrome is a rare, genetic, vascular disease characterized by congenital dysfunction of smooth muscle throughout the body, manifesting with cerebrovascular disease, aortic anomalies, intestinal hypoperistalsis, hypotonic bladder, and pulmonary hypertension. Congenital mid-dilated pupils non-reactive to light associated with a large, persistent patent ductus arteriosus are characteristic hallmarks of the disease.	Rare genetic gastroenterological disease;Rare genetic neurological disorder;Rare genetic vascular disease
Orphanet:404466	Female infertility due to zona pellucida defect	ZP2;ZP3;ZP1	3	Female infertility due to zona pellucida defect is a rare, genetic, female infertility disorder characterized by the presence of abnormal oocytes that lack a zona pellucida. Affected individuals are unable to conceive despite having normal menstrual cycles and sex hormone levels, as well as no obstructions in the fallopian tubes or defects of the uterus or adnexa.	Genetic infertility
Orphanet:404451	FBLN1-related developmental delay-central nervous system anomaly-syndactyly syndrome	FBLN1	1	 gene point mutation. Macular degeneration and signs of brain atrophy and spinal cord compression have also been reported.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:404454	Alacrimia-choreoathetosis-liver dysfunction syndrome	NGLY1	1	A rare, genetic, inborn error of metabolism disorder characterized by global developmental delay, hypotonia, choreoathetosis, hypo-/alacrimia, and liver dysfunction which manifests with elevated liver transanimases and hepatocyte cytoplasmic storage material or vacuolization on liver biposy. Additional features reported include acquired microcephaly, hypo-/areflexia, seizures, peripheral neuropathy, intellectual and language/speech disability, additional ocular anomalies and EEG and brain imaging abnomalities.	Rare genetic neurological disorder;Rare genetic skin disease;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:404443	Tall stature-intellectual disability-facial dysmorphism syndrome	DNMT3A	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:404448	ADNP syndrome	ADNP	1	A rare syndromic intellectual disability characterized by global developmental delay, gastrointestinal problems, hypotonia, delayed speech, behavioral and sleep problems, pain insensitivity, seizures, structural brain anomalies, dysmorphic features, visual problems, early tooth eruption and autistic features.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:404437	Diffuse cerebral and cerebellar atrophy-intractable seizures-progressive microcephaly syndrome	QARS	1	Diffuse cerebral and cerebellar atrophy-intractable seizures-progressive microcephaly syndrome is a rare, genetic, central nervous system malformation syndrome characterized by congenital, progressive microcephaly, neonatal to infancy-onset of severe, intractable seizures, and diffuse cerebral cortex and cerebellar vermis atrophy with mild cerebellar hemisphere atrophy, associated with profound global developmental delay. Hypotonia or hypertonia with brisk reflexes, variable dysmorphic facial features, ophthalmological signs (cortical visual impairment, nystagmus, eye deviation) and episodes of sudden extreme agitation caused by severe illness may also be associated.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:404440	Intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency	SETD5	1	Intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency is a rare, syndromic intellectual disability characterized by intellectual disability of various severity, hypotonia, feeding difficulties, dysmorphic features, autism and behavioral issues. Growth retardation, congenital heart anomalies, gastrointestinal and genitourinary defects have been rarely associated.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:404560	Familial atypical multiple mole melanoma syndrome	CDKN2A	1	50) and a family history of melanoma as well as, in a subset of patients, an increased risk of developing pancreatic cancer (see this term) and other malignancies.	Rare genetic tumor
Orphanet:404553	Vasculitis due to ADA2 deficiency	ADA2	1	Vasculitis due to ADA2 deficiency is a rare, genetic, systemic and rheumatologic disease due to adenosine deaminase-2 inactivating mutations, combining variable features of autoinflammation, vasculitis, and a mild immunodeficiency. Variable clinical presentation includes chronic or recurrent systemic inflammation with fever, livedo reticularis or racemosa, early-onset ischemic or hemorrhagic strokes, peripheral neuropathy, abdominal pain, hepatosplenomegaly, portal hypertension, cutaneous polyarteritis nodosa, variable cytopenia and immunoglobulin deficiency.	Rare genetic systemic or rheumatologic disease;Rare genetic immune disease
Orphanet:404546	DITRA	IL36RN	1	A rare, genetic, autoimflammatory syndrome with immune deficiency disease characterized by recurrent and severe flares of generalized pustular psoriasis associated with high fever, asthenia, and systemic inflammation, due to IL36R antagonist deficiency. Psoriatic nail changes (e.g. pitting and onychomadesis) and ichthyosis may occasionally be associated.	Rare genetic immune disease
Orphanet:404521	Spinal muscular atrophy with respiratory distress type 2	LAS1L	1	Spinal muscular atrophy with respiratory distress type 2 is a rare, genetic, motor neuron disease characterized by progressive early respiratory failure associated with diaphragm paralysis, distal muscular weakness, joint contractures, and axial hypotonia with preserved antigravity limb movements. Phenotype overlaps considerably with SMARD type 1 but is differentiated by a mutation in a different gene.	Rare genetic neurological disorder
Orphanet:404511	Clear cell papillary renal cell carcinoma	HNF1A;MITF;PBRM1	3	Clear cell papillary renal cell carcinoma is a rare, indolent subtype of clear cell renal carcinoma, arising from epithelial cells in the renal cortex. It most frequently manifests with a well-circumscribed, well-encapsulated, unicentric, unilateral, small tumor that typically does not metastasize. Clinically it can present with flank or abdominal pain or hematuria, although most patients are usually asymptomatic at the time of diagnosis. Bilateral and/or multifocal presentation should raise the suspicion of von Hippel-Lindau syndrome.	
Orphanet:404507	Chondromyxoid fibroma	GRM1	1	NA	
Orphanet:404499	Autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome due to RUBCN deficiency	RUBCN	1	An extremely rare, autosomal recessive, hereditary cerebellar ataxia disorder characterized by early onset of progressive, mild to moderate gait and limb ataxia, moderate to severe dysarthria, and nystagmus or saccadic pursuit, frequently associated with epilepsy, moderate intellectual disability, delayed speech acquisition, and hyporeflexia in the upper extremities. Hyperreflexia in the lower extremities may also be associated.	Rare genetic neurological disorder
Orphanet:404493	Autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome due to TUD deficiency	TDP2	1	A rare hereditary ataxia characterized by an early onset symptomatic generalized epilepsy, progressive cerebellar ataxia resulting in significant difficulties to walk or wheelchair dependency, and intellectual disability.	Rare genetic neurological disorder
Orphanet:404476	Global developmental delay-lung cysts-overgrowth-Wilms tumor syndrome	DICER1	1	Global developmental delay-lung cysts-overgrowth-Wilms tumor syndrome is a rare, genetic, overgrowth syndrome characterized by global developmental delay, macrosomia with subsequent somatic overgrowth, bilateral cystic lung lesions, congenital nephromegaly and bilateral Wilms tumor. Craniofacial dysmorphism includes macrocephaly, frontal bossing, large anterior fontanelle, mild hypertelorism, ear pit, flat nasal bridge, anteverted nares and mild micrognathia. Additional features may include brain and skeletal anomalies, enlarged protuberant abdomen, fat pads on dorsum of feet and toes, and rugated soles with skin folds, as well as umbilical/inguinal hernia and autistic behavior.	Rare genetic developmental defect during embryogenesis;Inherited cancer-predisposing syndrome
Orphanet:411536	Mild phosphoribosylpyrophosphate synthetase superactivity	PRPS1	1	Mild phosphoribosylpyrophosphate (PRPP) synthetase superactivity is the mild and late-onset form of PRPP synthetase superactivity (see this term), an X-linked disorder of purine metabolism associated with hyperuricemia and hyperuricosuria, leading to urolithiasis and gout. This form is not associated with any neuropathy or central nervous system (CNS) disorders.	Rare inborn errors of metabolism;Rare genetic renal disease;Rare genetic neurological disorder
Orphanet:411543	Severe phosphoribosylpyrophosphate synthetase superactivity	PRPS1	1	Severe phosphoribosylpyrophosphate (PRPP) synthetase superactivity is the severe and early-onset form of PRPP synthetase superactivity (see this term), an X-linked disorder of purine metabolism associated with hyperuricemia and hyperuricosuria, that is characterized by urolithiasis, gout and neurodevelopmental anomalies.	Rare inborn errors of metabolism;Rare genetic renal disease;Rare genetic neurological disorder
Orphanet:411590	Wolfram-like syndrome	WFS1	1	Wolfram-like syndrome is a rare endocrine disease characterized by the triad of adult-onset diabetes mellitus, progressive hearing loss (usually presenting in the first decade of life and principally of low to moderate frequencies), and/or juvenile-onset optic atrophy. Psychiatric (i.e. anxiety, depression, hallucinations) and sleep disorders, the only neurologic abnormalities observed in this disease, have been reported in rare cases. Unlike Wolfram syndrome, patients with Wolfram-like syndrome do not report endocrine or cardiac findings.	Genetic otorhinolaryngologic disease;Rare genetic eye disease;Rare genetic endocrine disease
Orphanet:411602	Hereditary late-onset Parkinson disease	SNCA;GBA;LRRK2;EIF4G1;VPS35;DNAJC13;GIGYF2	7	Hereditary late-onset Parkinson disease (LOPD) is a form of Parkinson disease (PD), characterized by an age of onset of more than 50 years, tremor at rest, gait complaints and falls, bradykinesia, rigidity and painful cramps. Patients usually present a low risk of developing non motor symptoms, dystonia, dyskinesia and levodopa-induced dyskinesia (LID).	Rare genetic neurological disorder
Orphanet:411629	Nephropathic infantile cystinosis	CTNS	1	Nephropathic infantile cystinosis is the most common and severe form of cystinosis (see this term), a metabolic disease characterized by an accumulation of cystine inside the lysosomes that causes damage in different organs and tissues, particularly in the kidneys and eyes.	Rare genetic renal disease;Rare inborn errors of metabolism
Orphanet:411493	Pontocerebellar hypoplasia type 10	CLP1	1	Pontocerebellar hypoplasia type 10 is a rare, genetic, pontocerebellar hypoplasia subtype characterized by severe psychomotor developmental delay, progressive microcephaly, progressive spasticity, seizures, and brain abnormalities consisting of mild atrophy of the cerebellum, pons and corpus callosum and cortical atrophy with delayed myelination. Patients may present dysmorphic facial features (high arched eyebrows, prominent eyes, long palpebral fissures and eyelashes, broad nasal root, and hypoplastic alae nasi) and an axonal sensorimotor neuropathy.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:411511	Angelman syndrome due to a point mutation	UBE3A	1	NA	Rare genetic neurological disorder
Orphanet:411515	Angelman syndrome due to imprinting defect in 15q11-q13	SNRPN;UBE3A;ATP10A	3	NA	Rare genetic neurological disorder
Orphanet:411712	Maternal riboflavin deficiency	SLC52A1	1	Maternal riboflavin deficiency is a rare, genetic disorder of metabolite absorption or transport characterized by persistently decreased riboflavin serum levels due to a primary genetic defect in the mother and which leads to clinical and biochemical findings consistent with a secondary, life-threatening, transient multiple acyl-CoA dehydrogenase deficiency (MADD) in the newborn. The mother usually presents hyperemesis gravidarum in the absence of other features of riboflavin deficiency, such as skin lesions, jaundice, pruritus, sore mucous membranes, visual disturbances.	Rare inborn errors of metabolism
Orphanet:411788	Familial isolated trichomegaly	FGF5	1	Familial isolated trichomegaly is a rare genetic hair anomaly characterized by a prolonged anagen phase of the eyelash hairs, leading to extreme eyelash growth that may result in corneal irritation. Increased growth of hair on other parts of the face (eyebrows, cheeks, forehead) and/or the body (chest, arms, legs) may be associated.	Rare genetic skin disease
Orphanet:411986	Early-onset epileptic encephalopathy-cortical blindness-intellectual disability-facial dysmorphism syndrome	DOCK7	1	Early-onset epileptic encephalopathy-cortical blindness-intellectual disability-facial dysmorphism syndrome is a rare, syndromic intellectual disability syndrome characterized by cortical blindness, different types of seizures, intellectual disability with limited or absent speech, and dysmorphic facial features. Brain imaging typically shows mild pontine hypoplasia, hypoplasia of the corpus callosum and atrophy in the occipital region.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:412022	Facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome	ASPH	1	Facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome is a syndromic developmental defect of the eye characterized by dislocated or subluxated crystalline lenses, anterior segment abnormalities, and distinctive facial features such as flat cheeks and a prominent, beaked nose. Affected individuals may develop nontraumatic conjunctival cysts, also referred to as filtering blebs.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:411641	Ocular cystinosis	CTNS	1	Ocular cystinosis is the benign, adult form of cystinosis (see this term), a metabolic disease characterized by an accumulation of cystine crystals in the cornea and conjunctiva responsible for tearing and photophobia and associated with no other additional manifestations.	Rare genetic eye disease;Rare inborn errors of metabolism
Orphanet:411634	Juvenile nephropathic cystinosis	CTNS	1	Nephropathic juvenile cystinosis is the intermediate form, in regards to severity and age of onset, of cystinosis (see this term), a metabolic disease characterized by an accumulation of cystine inside the lysosomes that causes damage in different organs and tissues, particularly in the kidneys and eyes.	Rare genetic renal disease;Rare inborn errors of metabolism
Orphanet:371364	Hypotonia-speech impairment-severe cognitive delay syndrome	NALCN;UNC80	2	Hypotonia-speech impairment-severe cognitive delay syndrome is a rare, genetic neurodegenerative disorder characterized by severe, persistent hypotonia (presenting at birth or in early infancy), severe global developmental delay (with poor or absent speech, difficulty or inability to roll, sit or walk), profound intellectual disability, and failure to thrive. Additional manifestations include microcephaly, progressive peripheral spasticity, bilateral strabismus and nystagmus, constipation, and variable dysmorphic facial features (including plagiocephaly, broad forehead, small nose, low-set ears, micrognathia and open mouth with tented upper lip).	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:391677	Short stature-optic atrophy-Pelger-Huët anomaly syndrome	NBAS	1	A rare, genetic, developmental defect during embryogenesis malformation syndrome characterized by severe postnatal growth retardation, craniofacial dysmorphism, which includes a progeroid facial appearance, brachycephaly with hypoplasia of the frontal and parietal tubers and a flat occipital area, narrow forehead, prominent glabella, small orbit, slight bilateral exophthalmos, straight nose, hypoplastic cheekbones, long philtrum and thin lips, skeletal abnormalities (i.e. micromelia, brachydactyly, and severe short stature with short limbs), normal intelligence, Pelger-Huët anomaly of leukocytes, loose skin with decreased tissue turgor, and bilateral optic atrophy with loss of color vision and visual acuity. Recurrent liver failure triggered by fever has been occasionally reported. Radiographs may evidence delayed bone age, late ossification and/or osteoporosis.	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:391474	Frontorhiny	ALX3	1	Frontorhiny is a distinct syndromic type of frontonasal malformation characterized by hypertelorism, wide nasal bridge, broad columella, widened philtrum, widely separated narrow nares, poor development of nasal tip, midline notch of the upper alveolus, columella base swellings and a low hairline. Additional features reported in some include upper eyelid ptosis and midline dermoid cysts of craniofacial structures and philtral pits or rugose folding behind the ears. An autosomal recessive inheritance has been proposed.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:391490	Adult-onset myasthenia gravis	TNFRSF11A;CTLA4;HLA-DQA1	3	A rare autoimmune disorder of the neuromuscular junction characterized by fatigable muscle weakness with frequent ocular signs and/or generalized muscle weakness, and occasionally associated with thymoma.	
Orphanet:391487	Autoimmune enteropathy and endocrinopathy-susceptibility to chronic infections syndrome	STAT1	1	An extremely rare, autosomal dominant immunological disorder characterized by variable enteropathy, endocrine disorders (e.g. type 1 diabetes mellitus, hypothyroidism), immune dysregulation with pulmonary and blood-borne bacterial infections, and fungal infections (chronic mucocutaneous candidiasis) developing in infancy. Other manifestations include short stature, eczema, hepatosplenomegaly, delayed puberty, and osteoporosis/osteopenia.	Rare genetic immune disease;Rare genetic gastroenterological disease;Rare genetic endocrine disease
Orphanet:391646	Feingold syndrome type 2	MIR17HG	1	Feingold syndrome type 2 (FS2) is a rare inherited malformation syndrome characterized by skeletal abnormalities and mild intellectual disabilities similar to those seen in Feingold syndrome type 1 (FS1; see this term) but that lacks the manifestations of gastrointestinal atresia and short palpebral fissures.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:391641	Feingold syndrome type 1	MYCN;MYCN	2	Feingold syndrome type 1 (FS1) is a rare inherited malformation syndrome characterized by microcephaly, short stature and numerous digital anomalies.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:391665	Homozygous familial hypercholesterolemia	ABCG5;ABCG8;APOB;LDLR;LDLRAP1;PCSK9	6	A rare disorder of lipid metabolism characterized by severely elevated low-density lipoprotein cholesterol levels and subsequent premature formation of atherosclerotic plaques in the coronary arteries, proximal aorta, and other arteries, significantly increasing the risk of cardiovascular disease at an early age. Xanthomas of the skin and in tendons are also a hallmark of the disease. Lethality is high due to early complications, in particular myocardial infarction.	Rare inborn errors of metabolism;Rare genetic endocrine disease
Orphanet:391343	Fatal post-viral neurodegenerative disorder	PRF1	1	Fatal post-viral neurodegenerative disorder is a rare neuroinflammatory disease characterized by the onset of ataxia, dysarthia and cerebral white matter changes which are triggered by viral infection. Episodic progressive neurodegeneration (manifesting with loss of motor and verbal skills, muscle weakness, further cerebral white matter degeneration and, eventually, death) is observed in the absence of hematopathology, cytokine overproduction, fever, hypertrigliceridemia, hypofibrinogenemia and hyperferritinemia.	Rare genetic neurological disorder
Orphanet:391348	Growth and developmental delay-hypotonia-vision impairment-lactic acidosis syndrome	SFXN4	1	Growth and developmental delay-hypotonia-vision impairment-lactic acidosis syndrome is a rare, genetic, mitochondrial oxidative phosphorylation disorder characterized by intrauterine growth retardation, microcephaly, hypotonia, vision impairment, speech and language delay and lactic acidosis with reduced respiratory chain activity (typically complex I). Additonal features may include macrocytic anemia, tremor, muscular atrophy, dysmetria and mild intellectual disability.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:391351	SURF1-related Charcot-Marie-Tooth disease type 4	SURF1	1	A subtype of Charcot-Marie-Tooth disease type 4 characterized by childhood onset of severe, progressive, demyelinating sensorimotor neuropathy manifesting with distal muscle weakness and atrophy of hands and feet, distal sensory impairment (vibration and pinprick) of lower limbs, lactic acidosis, areflexia and severely reduced motor nerve conduction velocities (25 m/s or less). Patients may also present kyphoscoliosis, nystagmus, hearing loss, cerebellar ataxia and/or brain MRI abnormalities (putaminal and periaqueductal lesions).	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:391366	Growth retardation-mild developmental delay-chronic hepatitis syndrome	SH2B3	1	Growth retardation-mild developmental delay-chronic hepatitis syndrome is a rare, genetic, parenchymatous liver disease characterized by pre- and postnatal growth retardation, mild global developmental delay, chronic hepatitis with hepatosplenomegaly, Hashimoto thyroiditis, thrombocytopenia, anemia, and B-precursor acute lymphoblastic leukemia.	Rare genetic hepatic disease
Orphanet:391372	Intellectual disability-severe speech delay-mild dysmorphism syndrome	FOXP1	1	Intellectual disability-severe speech delay-mild dysmorphism syndrome is a rare, genetic, syndromic intellectual disability disorder, with highly variable phenotype, typically characterized by mild to severe global development delay, severe speech and language impairment, mild to severe intellectual disability, dysphagia, hypotonia, relative to true macrocephaly, and behavioral problems that may include autistic features, hyperactivity, and mood lability. Facial gestalt typically features a broad, prominent forehead, hypertelorism, downslanting palpebral fissures, ptosis, a short bulbous nose with broad tip, thick vermilion border, wide, and open mouth with downturned corners. Brain, cardiac, urogenital and ocular malformations may be associated.	Rare genetic neurological disorder
Orphanet:391376	Congenital microcephaly-severe encephalopathy-progressive cerebral atrophy syndrome	ASNS	1	Congenital microcephaly-severe encephalopathy-progressive cerebral atrophy syndrome is a rare, genetic, neurometabolic disorder characterized by severe, progressive microcephaly, severe to profound global development delay, intellectual disability, seizures (typically tonic and/or myoclonic and frequently intractable), hyperekplexia, and axial hypotonia with appendicular spasticity, as well as hyperreflexia, dyskinetic quadriplegia, and abnormal brain morphology (cerebral atrophy with variable additional features including ventriculomeglay, pons and/or cerebellar hypoplasia, simplified gyral pattern and delayed myelination). Cortical blindness, feeding difficulties and respiratory insufficiency may also be associated.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:391389	Familial episodic pain syndrome with predominantly upper body involvement	TRPA1	1	Familial episodic pain syndrome with predominantly upper body involvement is a subtype of familial episodic pain syndrome characterized by episodes of severe debilitating pain mainly affecting shoulders, thorax and arms (occasionally radiating to the abdomen and legs), triggered by fasting, fatigue, cold temperatures or physical exercise, which last for 60-90 min and respond poorly to conventional analgesia. Intense pain episodes are accompanied by dyspnea, tachycardia, sweating, generalized pallor, peribuccal cyanosis, and stiffness of the abdominal wall and are followed by a period of exhaustion and somnolence.	Rare genetic neurological disorder
Orphanet:391392	Familial episodic pain syndrome with predominantly lower limb involvement	SCN11A	1	Familial episodic pain syndrome with predominantly lower limb involvement is a subtype of familial episodic pain syndrome characterized by intense, episodic and/or cyclic pain mainly localized in the distal lower limbs (occasionally affecting upper limbs as well) which is triggered/exacerbated by fatigue, cold exposure and/or weather changes and alleviated with anti-inflammatory medication, that has a tendancy to diminish in frequency with age. Episodes usually occur late in the day, last 15-30 min and associate sweating and a cold sensation of affected area.	Rare genetic neurological disorder
Orphanet:391397	Hereditary sensory and autonomic neuropathy type 7	SCN11A	1	A rare, genetic, periphery neuropathy characterized by a congenital insensitivity to pain, muscular hypotonia and gastrointestinal disturbances. Patients present with delayed motor milestones achievement, self-mutilations, skin ulcers, poor wound healing, painless fractures, hyperhidrosis, abdominal discomfort, diarrhea and/or constipation. Cognitive development is normal.	Rare genetic neurological disorder
Orphanet:391408	Primary microcephaly-mild intellectual disability-young-onset diabetes syndrome	PPP1R15B;TRMT10A	2	Primary microcephaly-mild intellectual disability-young-onset diabetes syndrome is a rare, genetic, syndromic intellectual disability disorder characterized by congenital, persistent microcephaly, low birth weight, short stature, childhood-onset seizures, global development delay, mild intellectual disability, and adolescent or young adult-onset diabetes mellitus. Gait ataxia, skeletal abnormalities, dorsocervical fat pad, and infantile cirrhosis may also be associated. Brain morphology is typically normal, although delayed myelination and hypoplastic brainstem have been reported.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease
Orphanet:391411	Atypical juvenile parkinsonism	PODXL;DNAJC6;SYNJ1	3	A complex form of young-onset Parkinson disease that manifests with pyramidal signs, eye movement abnormalities, psychiatric manifestations (depression, anxiety, drug-induced psychosis, and impulse control disorders), intellectual disability, and other neurological symptoms (such as ataxia and epilepsy) along with classical parkinsonian symptoms.	Rare genetic neurological disorder
Orphanet:391428	HSD10 disease, infantile type	HSD17B10	1	HSD10 disease, infantile type is a clinical subtype of HSD10 disease, a rare neurometabolic disorder. Affected boys may show lethargy, poor feeding and evidence of mitochondrial dysfunction in the newborn period, with subsequent mild developmental delay and abnormal muscle tone. Hallmark of the disease is progressive neurodegeneration and cardiomyopathy, which usually manifests between ages 6 months and 2 years with developmental regression, progressive visual and hearing loss, epilepsy and other neurological symptoms, and severe cardiomyopathy. Laboratory investigations show signs of mitochondrial dysfunction, and increased urinary excretion of specific isoleucine metabolites. The disease is often fatal around 2-4 years of age.	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:391457	HSD10 disease, neonatal type	HSD17B10	1	HSD10 disease, neonatal type is the most severe form of HSD10 disease, a rare neurometabolic disorder. It is characterized by severe metabolic/lactic acidosis in the neonatal period, little psychomotor development, seizures and severe progressive hypertrophic cardiomyopathy. Hepatic involvement and coagulopathy are rare. The disease is fatal within the first months of life.	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:391307	Severe intellectual disability-short stature-behavioral abnormalities-facial dysmorphism syndrome	TTI2	1	Severe intellectual disability-short stature-behavioral abnormalities-facial dysmorphism syndrome is a rare, genetic, syndromic intellectual disability disorder characterized by severe intellectual disability with limited or absent speech and language, short stature, acquired microcephaly, kyphoscoliosis or scoliosis, and behavioral disturbances that include hyperactivity, stereotypy and aggressiveness. Facial dysmorphism, that typically includes sloping forehead, mild synophrys, deep-set eyes, strabismus, anteverted large ears, prominent nose and dental malposition, is also characteristic.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:391316	Infantile-onset mesial temporal lobe epilepsy with severe cognitive regression	TNK2	1	Infantile-onset mesial temporal lobe epilepsy with severe cognitive regression is a rare monogenic disease with infantile-onset pharmacoresistant focal seizures of mesial temporal lobe onset manifesting with unresponsiveness, hypertonia and automatisms and cognitive regression soon after seizure onset leading to severe intellectual disability with behavioral abnormalities.	Rare genetic neurological disorder
Orphanet:391311	Susceptibility to viral and mycobacterial infections	STAT1	1	Susceptibility to viral and mycobacterial infections is a rare, genetic, primary immunodeficiency due to a defect in innate immunity disorder characterized by impaired intracellular signaling from both type I and type II interferons, leading to early-onset, severe, life-threatening intracellular bacterial (typically mycobacteria) and viral (mainly herpes viruses) infections.	Rare genetic immune disease
Orphanet:391320	East Texas bleeding disorder	F5	1	East Texas bleeding disorder is a rare, genetic, coagulation disorder characterized by easy bruising (without hemarthrosis or spontaneous hematomas), epistaxis, menorrhagia, and excessive bleeding after minor trauma and surgical procedures. Patients present a prolonged prothrombin time and/or activated partial thromboplastin time, normal levels of all coagulation factors, and normal protein C activity.	Rare genetic hematologic disease
Orphanet:391330	X-linked osteoporosis with fractures	PLS3	1	X-linked osteoporosis with fractures is a rare, genetic, primary bone dysplasia with decreased bone density disorder characterized by childhood-onset osteoporosis associated with recurrent, multiple, osteoporotic, long bone fractures and/or vertebral compression fractures, significant height loss in adulthood, low bone mineral density scores, and otherwise no other abnormalities. Heterozygote females may be unaffected or have a milder phenotype.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:397968	Charcot-Marie-Tooth disease type 2R	TRIM2	1	Charcot-Marie-Tooth disease type 2R is a rare subtype of axonal hereditary motor and sensory neuropathy characterized by early-onset axial hypotonia, generalized muscle weakness, absent deep tendon reflexes and decreased muscle mass. Electromyography reveals decreased motor nerve conduction velocities with markedly reduced sensory and motor amplitudes.	Rare genetic neurological disorder
Orphanet:397964	Combined immunodeficiency due to MALT1 deficiency	MALT1	1	Combined immunodeficiency due to MALT1 deficiency is a rare, genetic form of primary immunodeficiency characterized by growth retardation, early recurrent pulmonary infections leading to bronchiectasis, inflammatory gastrointestinal disease, and other symptoms, such as rash, dermatitis, skin infections.	Rare genetic immune disease
Orphanet:397959	TCR-alpha-beta-positive T-cell deficiency	TRAC	1	TCR-alpha-beta-positive T-cell deficiency is a rare, hereditary primary immunodeficiency characterized by recurrent respiratory tract infection, otitis media, candidiasis, diarrhea, as well as various signs and symptoms of immune dysregulation (hypereosinophilia, eczema, vitiligo, alopecia areata, autoimmune hemolytic anemia, pityriasis rubra pilaris). Failure to thrive, moderate lymphadenopathy and hepatomegaly have also been reported.	Rare genetic immune disease
Orphanet:397951	Microcephaly-thin corpus callosum-intellectual disability syndrome	TAF2	1	A rare, genetic, syndromic intellectual disability disease characterized by progressive postnatal microcephaly and global developmental delay, as well as moderate to profound intellectual disability, difficulty or inability to walk, pyramidal signs (including spasticity, hyperreflexia and extensor plantar response) and thin corpus callosum revealed by brain imaging. Ophthalmologic signs (including nystagmus, strabismus and abnormal retinal pigmentation), foot deformity and genital anomalies may also be associated.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:397946	Autosomal spastic paraplegia type 58	KIF1C	1	A rare, complex subtype of hereditary spastic paraplegia characterized by variable onset of slowly progressive lower limb spasticity and weakness and prominent cerebellar ataxia, associated with gait disturbances, dysarthria, increased deep tendon reflexes and extensor plantar responses. Additional features may include involuntary movements (i.e. clonus, tremor, fasciculations, chorea), decreased vibration sense, oculomotor abnormalities (e.g. nystagmus) and distal amyotrophy in the upper and lower limbs.	Rare genetic neurological disorder
Orphanet:397941	MAN1B1-CDG	MAN1B1	1	 (9q34.3).	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:397937	Polyglucosan body myopathy type 1	RBCK1	1	Polyglucosan body myopathy type 1 is a rare, genetic, glycogen storage disorder characterized by polyglucosan accumulation in various tissues, manifesting with progressive proximal muscle weakness in the lower limbs and rapidly progressive, usually dilated, cardiomyopathy. Hepatic involvement and growth retardation may be associated. Early-onset immunodeficiency and autoinflammation, presenting with recurrent bacterial infections, have also been reported.	Rare genetic cardiac disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:397933	Severe intellectual disability-progressive postnatal microcephaly-midline stereotypic hand movements syndrome	IQSEC2	1	Severe intellectual disability-progressive postnatal microcephaly-midline stereotypic hand movements syndrome is a rare, genetic, syndromic intellectual disability disorder characterized by severe intellectual disability, non-inherited, progressive, post-natal microcephaly, hypotonia, hyperkinesia, absence of speech, strabismus, and midline stereotypic hand movements (e.g. hand washing/rubbing). Additional features include developmental delay, seizures and behavioral disturbances, such as self injury and unexplained crying episodes.	Rare genetic neurological disorder
Orphanet:397927	Sacral agenesis-abnormal ossification of the vertebral bodies-persistent notochordal canal syndrome	TBXT	1	Sacral agenesis-abnormal ossification of the vertebral bodies-persistent notochordal canal syndrome is a rare, genetic, neural tube defect malformation syndrome characterized by sacral agenesis and abnormal vertebral body ossification with normal vertebral arches associated with notochord canal persistence on ultrasonography. Additional findings include bilateral clubfoot, oligohydramnios, single umbilical artery and, in some, increased nuchal translucency.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:397922	Ferro-cerebro-cutaneous syndrome	PIGA	1	Ferro-cerebro-cutaneous syndrome is a rare, genetic, metabolic liver disease characterized by progressive neurodegeneration, cutaneous abnormalities, including varying degrees of ichthyosis or seborrheic dermatitis, and systemic iron overload. Patients manifest with infantile-onset seizures, encephalopathy, abnormal eye movements, axial hypotonia with peripheral hypertonia, brisk reflexes, cortical blindness and deafness, myoclonus and hepato/splenomegaly, as well as oral manifestations, including microdontia, wiedely spaced and pointed teeth with delayed eruption, and gingival overgrowth.	Rare genetic neurological disorder;Rare genetic hepatic disease
Orphanet:397787	Severe combined immunodeficiency due to IKK2 deficiency	IKBKB	1	Severe combined immunodeficiency due to IKK2 deficiency is a rare, genetic form of primary immunodeficiency characterized by life-threatening bacterial, fungal and viral infections with the onset in infancy, and failure to thrive. Typically, hypogammaglobulinemia or agammaglobulinemia and normal levels of T and B cells are present.	Rare genetic immune disease
Orphanet:397755	Periodic paralysis with transient compartment-like syndrome	CACNA1S	1	Periodic paralysis with transient compartment-like syndrome is a rare, genetic, neuromuscular disease characterized by normokalemic episodes of painful muscle cramping followed by progressive, permanent, flaccid weakness, triggered by stress, cold and exercise, associated with myopathic myopathy and painful acute edema with neuronal compression, foot drop and muscle degeneration when located in the tibialis anterior muscle group.	Rare genetic neurological disorder
Orphanet:397758	Retinal dystrophy with inner retinal dysfunction and ganglion cell anomalies	ITM2B	1	Retinal dystrophy with inner retinal dysfunction and ganglion cell anomalies is a rare, genetic, retinal dystrophy disorder characterized by decreased central retinal sensitivity associated with hyper-reflectivity of ganglion cells and nerve fiber layer with loss of optic nerve fibers manifesting with fotophobia, optic disc pallor and progressive loss of central vision with preservation of peripheral visual field.	Rare genetic eye disease
Orphanet:397744	Peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome	MYH14	1	Peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome is a rare, syndromic genetic deafness characterized by a combination of muscle weakness, chronic neuropathic and myopathic features, hoarseness and sensorineural hearing loss. A wide range of disease onset and severity has been reported even within the same family.	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder
Orphanet:397750	Periodic paralysis with later-onset distal motor neuropathy	MT-ATP6;MT-ATP8	2	Periodic paralysis with later-onset distal motor neuropathy is a rare, genetic, neuromuscular disease characterized by acute episodic muscle weakness in upper and lower extremities (which responds to acetazolamide treatment) associated with later-onset, chronic, slowly progressive, distal, axonal neuropathy.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:397725	COASY protein-associated neurodegeneration	COASY	1	COASY protein-associated neurodegeneration (CoPAN) is a very rare, slowly progressive form of neurodegeneration with brain iron accumulation (NBIA) characterized by classic NBIA features. The clinical manifestations include early-onset spastic-dystonic paraparesis, oromandibular dystonia, dysarthria, parkinsonism, axonal neuropathy, progressive cognitive impairment, complex motor tics, and obsessive-compulsive disorder.	Rare genetic neurological disorder
Orphanet:397735	Autosomal dominant Charcot-Marie-Tooth disease type 2U	MARS	1	A subtype of autosomal dominant Charcot-Marie-Tooth disease type 2, characterized by late adult-onset (50-60 years of age) of slowly progressive, axonal, peripheral sensorimotor neuropathy resulting in distal upper limb and proximal and distal lower limb muscle weakness and atrophy, in conjunction with distal, panmodal sensory impairment in upper and lower limbs. Tendon reflexes are reduced and nerve conduction velocities range from reduced to absent. Neuropathic pain has also been associated.	Rare genetic neurological disorder
Orphanet:397709	Intellectual disability-coarse face-macrocephaly-cerebellar hypotrophy syndrome	SNX14	1	Intellectual disability-coarse face-macrocephaly-cerebellar hypotrophy syndrome is a rare, genetic, central nervous system malformation syndrome characterized by early-onset, progressive, severe cerebellar ataxia associated with progressive, moderate to severe intellecutal disability, global developmental delay, progressively coarsening facial features, relative macrocephaly and absence of seizures. Sensorineural hearing loss may be associated. Neuroimaging reveals cerebellar atrophy/hypoplasia.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:397715	Joubert syndrome with Jeune asphyxiating thoracic dystrophy	CSPP1;KIAA0586	2	Joubert syndrome with Jeune asphyxiating thoracic dystrophy (JATD) is an extremely rare genetic bone disorder characterized by the classic features of Joubert syndrome (i.e. malformation of the brainstem causing ataxia, hypotonia,cognitive impairment, and abnormal eyemovements), associated with the skeletal anomalies found in JATD including short-rib dysplasia and narrow thorax causing respiratory failure, short limbs, and metaphyseal changes.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease;Rare genetic neurological disorder
Orphanet:397692	Hereditary isolated aplastic anemia	THPO;MPL;ACD	3	Hereditary isolated aplastic anemia is a rare, genetic, constitutional aplastic anemia disorder characterized by severe peripheral blood pancytopenia and bone marrow hypoplasia in multiple individuals of a family, in the absence of any somatic symptoms. Abnormal bleeding, as well as erythrocyte macrocytosis, is reported and patients usually become transfusion-dependent.	Rare genetic hematologic disease
Orphanet:397623	Short stature-auditory canal atresia-mandibular hypoplasia-skeletal anomalies syndrome	GSC	1	Short stature-auditory canal atresia-mandibular hypoplasia-skeletal anomalies syndrome is a rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by short stature, conductive hearing loss due to bilateral auditory canal atresia, mandibular hypoplasia and multiple skeletal abnormalities, including bilateral humeral hypoplasia, humeroscapular synostosis, delayed pubis rami ossification, central dislocation of the hips, and proximal femora defects, as well as bilateral talipes equinovarus, proximally implanted thumbs and lumbar hyperlordosis. Associated craniofacial dysmorphism includes micro/scaphocephaly, malar hypoplasia, high-arched palate, and simple, dysplastic pinnae with prearicular pits/tags.	Rare genetic developmental defect during embryogenesis;Genetic otorhinolaryngologic disease;Rare genetic bone disease
Orphanet:397685	Familial hyperprolactinemia	PRLR	1	Familial hyperprolactinemia is a rare, genetic endocrine disorder characterized by persistently high prolactin serum levels (not associated with gestation, puerperium, drug intake or pituitary tumor) in multiple members of a family. Clinically it manifests with signs usually observed in hyperprolactinemia, which are: secondary medroxyprogesterone acetate (MPA)-negative amenorrhea and galactorrhea in female patients, and hypogonadism and decreased testosterone level-driven sexual dysfunction in male patients. Oligomenorrhea and primary infertility have also been reported in some female patients.	Genetic infertility;Rare genetic endocrine disease
Orphanet:397615	Obesity due to CEP19 deficiency	CEP19	1	A rare, genetic form of obesity characterized by morbid obesity, hypertension, type 2 diabetes mellitus and dyslipidemia leading to early coronary disease, myocardial infarction and congestive heart failure. Intellectual disability and decreased sperm counts or azoospermia have also been reported.	Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease
Orphanet:397618	Foveal hypoplasia-optic nerve decussation defect-anterior segment dysgenesis syndrome	SLC38A8	1	Foveal hypoplasia-optic nerve decussation defect-anterior segment dysgenesis syndrome is a rare, genetic, eye disease characterized by foveal hypoplasia, optic nerve misrouting with an increased number of axons decussating at the optic chiasm and innervating the contralateral cortex, and posterior embryotoxon or Axenfeld anomaly (indicating anterior segment dysgenesis), in the absence of albinism. Patients present congenital nystagmus, decreased visual acuity, refractive errors and, ocassionally, strabismus. Microphthalmia and retinochoroidal coloboma may also be associated.	Rare genetic eye disease
Orphanet:397596	Activated PI3K-delta syndrome	PTEN;PIK3R1;PIK3CD	3	A rare, genetic, primary immunodeficiency disease characterized by increased susceptibility to recurrent and/or severe bacterial and viral infections (in particular, sinopulmonary bacterial and herpesvirus infections), chronic benign lymphoproliferation (manifesting as lympadenopathy, hepatosplenomegaly and focal nodular lymphoid hyperplasia), and/or autoimmune disease (including immune cytopenias, juvenile arthritis, glomerulonephritis and sclerosing cholangitis). Immunophenotypically, variable degrees of agammaglobulinemia with increased IgM levels, increased circulating transitional B cells, decreased naïve CD4 and CD8 T-cells with increased CD8 effector/memory T cells are observed.	Rare genetic immune disease
Orphanet:397593	Severe neonatal lactic acidosis due to NFS1-ISD11 complex deficiency	LYRM4;NFS1	2	Severe neonatal lactic acidosis due to NFS1-ISD11 complex deficiency is a rare, hereditary, mitochondrial oxidative phosphorylation disorder characterized by severe neonatal lactic acidosis and deficiency of mitochondrial complexes I, II and III. Clinical features are variable and may include hypotonia, respiratory distress with cyanosis, failure to thrive, feeding difficulties, hypoglycemia, dehydration, vomiting, seizures, and a risk of multiple organ failure.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:397612	Macrocephaly-developmental delay syndrome	KPTN	1	Macrocephaly-developmental delay syndrome is a rare, intellectual disability syndrome characterized by macrocephaly, mild dysmorphic features (frontal bossing, long face, hooded eye lids with small, downslanting palpebral fissures, broad nasal bridge, and prominent chin), global neurodevelopmental delay, behavioral abnormalities (e.g. anxiety, stereotyped movements) and absence or generalized tonic-clonic seizures. Additional features reported in some patients include craniosynostosis, fifth finger clinodactyly, recurrent pneumonia, and hepatosplenomegaly.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:397606	PrP systemic amyloidosis	PRNP	1	 (20p13) leading to deposition of prion protein amyloid.	Rare genetic neurological disorder
Orphanet:397590	Silver-Russell syndrome due to a point mutation	IGF2;CDKN1C	2	NA	Inherited cancer-predisposing syndrome;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:394532	Multiple acyl-CoA dehydrogenase deficiency, mild type	SLC25A32;FLAD1;ETFA;ETFB;ETFDH	5	NA	Rare genetic cardiac disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:394529	Multiple acyl-CoA dehydrogenase deficiency, severe neonatal type	ETFA;ETFB;ETFDH;FLAD1	4	NA	Rare genetic cardiac disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:399808	Male infertility with teratozoospermia due to single gene mutation	NANOS1	1	Male infertility with teratozoospermia due to single gene mutation is a rare, genetic male infertility due to sperm disorder characterized by the presence of spermatozoa with abnormal morphology, such as macrozoospermia or globozoospermia, in over 85% of sperm, resulting from mutation in a single gene known to cause teratozoospermia. It is a heterogeneous group that includes a wide range of abnormal sperm phenotypes affecting, solely or simultaneously, head, neck, midpiece, and/or tail.	Genetic infertility
Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation	TDRD9;FANCM;TEX15;CFTR;NR5A1;NANOS1;TAF4B;ZMYND15;TEX11;SYCP3;SOHLH1;XRCC2;SYCE1;MEIOB;KLHL10	15	Male infertility with azoospermia or oligospermia due to single gene mutation is a rare, genetic male infertility due to sperm disorder characterized by the absence of a measurable amount of spermatozoa in the ejaculate (azoospermia), or a number of sperm in the ejaculate inferior to 15 million/mL (oligozoospermia), resulting from a mutation in a single gene known to cause azoo- or oligo-spermia. Sperm morphology may be normal.	Genetic infertility
Orphanet:399058	Alpha-B crystallin-related late-onset myopathy	CRYAB	1	A rare, genetic, alpha-crystallinopathy disease characterized by adult-onset myofibrillar myopathy, variably associated with cardiomyopathy and/or posterior pole cataracts. Patients typically present progressive proximal and distal muscle weakness and wasting of lower and upper limbs, often with velopharyngeal involvement including dysphagia, dysphonia and ventilatory insufficiency. Electromyography shows myopathic features and muscle biopsy reveals myofibrillar myopthay changes.	Rare genetic cardiac disease;Rare genetic neurological disorder
Orphanet:399081	KLHL9-related early-onset distal myopathy	KLHL9	1	KLHL9-related early-onset distal myopathy is a rare, genetic distal myopathy characterized by slowly progressive distal limb muscle weakness and atrophy (beginning with anterior tibial muscle involvement followed by the intrinsic hand muscles) in association with reduced sensation in a stocking-glove distribution. Patients present with high stepping gait, ankle areflexia and contractures in the first to second decade of life, associated with marked ankle extensor muscle atrophy; later proximal muscle involvement is moderate and ambulation is preserved throughout the life.	Rare genetic neurological disorder
Orphanet:399103	Distal nebulin myopathy	NEB	1	Distal nebulin myopathy is a rare, slowly progressive, autosomal recessive distal myopathy characterized by early onset of predominantly distal muscle weakness and atrophy affecting lower leg extensor muscles, finger extensors and neck flexors. Muscle histology does not always show nemaline rods.	Rare genetic neurological disorder
Orphanet:399096	Distal anoctaminopathy	ANO5	1	Distal anoctaminopathy is a rare, autosomal recessive distal myopathy characterized by early adult-onset, slowly progressive, often asymmetrical, lower limb muscle weakness initially affecting the calves (with relative anterior muscle sparing) and later proximal muscle involvement, as well as highly elevated creatine kinase (CK) serum levels.	Rare genetic neurological disorder
Orphanet:398189	Focal facial dermal dysplasia type IV	CYP26C1	1	Focal facial dermal dysplasia type IV (FFDD4) is a rare focal facial dysplasia (FFDD; see this term), characterized by congenital isolated preauricular and/or cheek blister scar-like lesions.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:398069	Prader-Willi syndrome due to a point mutation	MAGEL2	1	NA	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility;Rare genetic developmental defect during embryogenesis
Orphanet:398079	Prader-Willi-like syndrome due to a point mutation	SIM1	1	NA	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility;Rare genetic developmental defect during embryogenesis
Orphanet:398088	Hereditary cryohydrocytosis with normal stomatin	SLC4A1	1	Hereditary cryohydrocytosis with normal stomatin is a rare, hereditary, hemolytic anemia due to a red cell membrane anomaly characterized by fatigue, mild anemia and pseudohyperkalemia due to a potassium leak from the red blood cells. A hallmark of this condition is that red blood cells lyse on storage at 4 degrees centigrade.	Rare genetic hematologic disease
Orphanet:435628	Keppen-Lubinsky syndrome	KCNJ6	1	A rare, genetic, primary lipodystrophy syndrome characterized by severe developmental delay and intellectual disability, hypertonia, hyperreflexia, microcephaly, tightly adherent skin, an aged appearance, severe generalized lipodystrophy, and distinct facial dysmorphism which includes large prominent eyes, narrow nasal bridge, tented upper lip vermilion, an open mouth, and high-arched palate. Laboratory analysis of serum and urine are normal.	Rare genetic neurological disorder;Rare genetic skin disease;Rare genetic endocrine disease
Orphanet:435660	LIPE-related familial partial lipodystrophy	LIPE	1	A rare, genetic lipodystrophy characterized by abnormal subcutaneous fat distribution, resulting in excess accumulation of fat in the face, neck, shoulders, axillae, trunk and pubic region, and loss of subcutaneous fat from the lower extremities. Variable common additional features are progressive adult onset myopathy, insulin resistance, diabetes, hypertriglyceridemia, hepatic steatosis, and vitiligo.	Rare genetic skin disease;Rare genetic endocrine disease
Orphanet:435651	CIDEC-related familial partial lipodystrophy	CIDEC	1	A rare, genetic lipodystrophy characterized by abnormal subcutaneous fat distribution, resulting in preservation of visceral, neck and axilliary fat and absence of lower limb and femorogluteal subcutaneous fat. Additional clinical features are acanthosis nigricans, insulin-resistant type II diabetes mellitus, dyslipidemia, and hypertension, leading to pancreatitis, hepatomegaly and hepatic steatosis.	Rare genetic skin disease;Rare genetic endocrine disease
Orphanet:435804	Short stature-advanced bone age-early-onset osteoarthritis syndrome	ACAN	1	A rare, primary bone dysplasia characterized by proportional short stature, early cessation of bone growth, accelerated skeletal maturation, variable presence of early-onset osteoarthritis and osteochondritis dissecans, and normal endocrine evaluation. The variable dysmorphic features include mild to relative macrocephaly, frontal bossing, midfacial hypoplasia, flat nasal bridge, brachydactyly, broad thumbs, and lordosis.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:435845	Lethal neonatal spasticity-epileptic encephalopathy syndrome	BRAT1	1	NA	Rare genetic neurological disorder
Orphanet:435930	Colobomatous optic disc-macular atrophy-chorioretinopathy syndrome	SIX6	1	NA	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:435819	Autosomal dominant Charcot-Marie-Tooth disease type 2 due to TFG mutation	TFG	1	A rare, axonal hereditary motor and sensory neuropathy characterized by adult onset of slowly progressive distal muscle weakness and atrophy, decreased deep tendon reflexes of lower limbs, and mild distal sensory loss leading to gait difficulties in most patients.	Rare genetic neurological disorder
Orphanet:435953	Progeroid features-hepatocellular carcinoma predisposition syndrome	SPRTN	1	NA	Rare genetic developmental defect during embryogenesis
Orphanet:435988	Chronic atrial and intestinal dysrhythmia syndrome	SGO1	1	NA	Rare genetic cardiac disease;Rare genetic gastroenterological disease
Orphanet:435934	COG2-CDG	COG2	1	 gene and characterized by normal presentation at birth, followed by progressive deterioration with postnatal microcephaly, developmental delay, intellectual disability, seizures, spastic quadriplegia, liver dysfunction, hypocupremia and hypoceruloplasminemia in the first year of life. Diffuse cerebral atrophy and thin corpus callosum may be observed on brain MRI.	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:435938	X-linked microcephaly-growth retardation-prognathism-cryptorchidism syndrome	RPL10	1	X-linked microcephaly-growth retardation-prognathism-cryptorchidism syndrome is a rare syndromic intellectual disability characterized by hypotonia, microcephaly, severe developmental delay, seizures, intellectual disability, growth retardation, cardiovascular septal defects, cryptorchidism, hypospadias, and dysmorphic features - prominent ears, prognathism, thin upper lip, dental crowding.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:436144	Intrauterine growth restriction-short stature-early adult-onset diabetes syndrome	CDKN1C	1	NA	Rare genetic endocrine disease
Orphanet:435998	Autosomal recessive intermediate Charcot-Marie-Tooth disease type D	COX6A1	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:436159	Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency	CTLA4	1	A rare, primary immunodeficiency characterized by variable combination of enteropathy, hypogammaglobulinemia, recurrent respiratory infections, granulomatous lymphocytic interstitial lung disease, lymphocytic infiltration of non-lymphoid organs (intestine, lung, brain, bone marrow, kidney), autoimmune thrombocytopenia or neutropenia, autoimmune hemolytic anemia and lymphadenopathy.	Rare genetic gastroenterological disease;Inherited cancer-predisposing syndrome;Rare genetic immune disease
Orphanet:436151	Intellectual disability-expressive aphasia-facial dysmorphism syndrome	SETBP1	1	NA	Rare genetic neurological disorder
Orphanet:436169	Thrombomodulin-related bleeding disorder	THBD	1	NA	Rare genetic hematologic disease
Orphanet:436166	Periodic fever-infantile enterocolitis-autoinflammatory syndrome	NLRC4	1	NA	Rare genetic systemic or rheumatologic disease
Orphanet:436182	Microcephalic primordial dwarfism-insulin resistance syndrome	NSMCE2;XRCC4	2	NA	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease
Orphanet:436174	Cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome	IARS2	1	NA	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare inborn errors of metabolism;Rare genetic endocrine disease
Orphanet:436245	Retinitis pigmentosa-juvenile cataract-short stature-intellectual disability syndrome	RDH11	1	A rare, genetic, syndromic rod-cone dystrophy disorder characterized by psychomotor developmental delay from early childhood, intellectual disability, short stature, mild facial dysmorphism (e.g. upslanted palpebral fissures, hypoplastic alae nasi, malar hypoplasia, attached earlobes), excessive dental spacing and malocclusion, juvenile cataract and ophthalmologic findings of atypical retinitis pigmentosa (i.e. salt-and-pepper retinopathy, attenuated retinal arterioles, generalized rod-cone dysfunction, mottled macula, peripapillary sparing of retinal pigment epithelium).	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:436242	Familial atrial tachyarrhythmia-infra-Hisian cardiac conduction disease	TNNI3K	1	NA	Rare genetic cardiac disease
Orphanet:436271	Non-progressive predominantly posterior cavitating leukoencephalopathy with peripheral neuropathy	APOPT1	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:436252	Combined immunodeficiency-enteropathy spectrum	TTC7A	1	NA	Rare genetic immune disease;Rare genetic developmental defect during embryogenesis
Orphanet:436274	Pseudoxanthoma elasticum-like skin manifestations with retinitis pigmentosa	GGCX	1	A rare, genetic, dermis elastic tissue disorder characterized by yellowish skin papules (resembling pseudoxanthoma elasticum) located on the neck, chest and/or flexural areas associated with loose, redundant, sagging skin on trunk and upper limbs, and retinitis pigmentosa, in the absence of clotting abnormalities. Patients present reduced night and peripheral vision, as well as optic nerve pallor, retinal pigment epithelium loss, attenuated retinal vessels and/or black pigment intra-retinal clumps.	Rare genetic eye disease;Rare genetic skin disease
Orphanet:437552	Autosomal recessive primary immunodeficiency with defective spontaneous natural killer cell cytotoxicity	FCGR3A	1	A rare, genetic primary immunodeficiency characterized by recurrent respiratory and skin viral infections (Ebstein-Barr virus, herpes simplex virus, human papillomavirus), deficient spontaneous cytotoxicity of natural killer cells, but preserved antibody-dependent cellular cytotoxicity. No other abnormalities are present on immunologic work-up.	Rare genetic immune disease
Orphanet:437572	MYH7-related late-onset scapuloperoneal muscular dystrophy	MYH7	1	NA	Rare genetic neurological disorder
Orphanet:438178	Severe intellectual disability-epilepsy-cataract syndrome due to fatty acyl-CoA reductase 1 deficiency	FAR1	1	NA	Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:438159	STAT3-related early-onset multisystem autoimmune disease	STAT3	1	A rare, genetic, lypmhoproliferative syndrome characterized by early onset recurrent infections, lymphadenopathy with hepatosplenomegaly and variabe autoimmune disorders, including hemolytic anemia, thrombocytopenia, neutropenia, enteropathy, type I diabetes, scleroderma, arthritis, atopic dermatitis, and inflammatory lung disease. Patients commonly have failure to thrive. Variable immunologic findings include decreased regulatory T-cells, hypogammaglobulinemia, and reduction in memory B cells.	Rare genetic gastroenterological disease;Inherited cancer-predisposing syndrome;Rare genetic immune disease
Orphanet:438134	PCNA-related progressive neurodegenerative photosensitivity syndrome	PCNA	1	 gene and characterized by neurodegeneration, postnatal growth retardation, prelingual sensorineural hearing loss, premature aging, ocular and cutaneous telangiectasia, learning difficulties, photophobia, and photosensitivity with evidence of predisposition to sun-induced malignancy. Progressive neurologic deterioration leads to gait disturbances, muscle weakness, speech and swallowing difficulties and progressive cognitive decline.	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder;Inherited cancer-predisposing syndrome;Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:438117	Steel syndrome	COL27A1	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:438114	RARS-related autosomal recessive hypomyelinating leukodystrophy	RARS	1	A rare, genetic leukodystrophy characterized by developmental delay, increased muscle tone leading later to spasticity, mild ataxia, nystagmus, dysarthria, intentional tremor, and mild intellectual disability. Brain imaging reveals supratentorial and infratentorial hypomyelination.	Rare genetic neurological disorder
Orphanet:438075	Ketoacidosis due to monocarboxylate transporter-1 deficiency	SLC16A1	1	NA	Rare inborn errors of metabolism
Orphanet:438274	GCGR-related hyperglucagonemia	GCGR	1	 gene characterized by pancreatic alpha cell hyperplasia, pancreatic neuroendocrine tumors and markedly increased serum glucagon levels in the absence of a glucagonoma syndrome. Clinical manifestations may include abdominal pain, pancreatitis, fatigue, diarrhea, and diabetes mellitus.	
Orphanet:438216	PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome due to a point mutation	PURA	1	PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome due to a point mutation is a rare, genetic neurological disease, with a highly variable phenotype, typically characterized by neonatal hypotonia, respiratory and feeding difficulties, global development delay (often with nonverbal and frequently non-ambulatory progression) and myopathic facies. Other frequently present features include seizures (or seizure-like episodes), visual impairment and encephalopathy.	Rare genetic developmental defect during embryogenesis
Orphanet:438207	Severe autosomal recessive macrothrombocytopenia	PRKACG	1	NA	Rare genetic hematologic disease
Orphanet:439212	Early-onset myopathy-areflexia-respiratory distress-dysphagia syndrome	MEGF10	1	NA	Rare genetic neurological disorder
Orphanet:439218	KCNQ2-related epileptic encephalopathy	KCNQ2	1	KCNQ2-related epileptic encephalopathy is a severe form of neonatal epilepsy that usually manifests in newborns during the first week of life with seizures (that affect alternatively both sides of the body), often accompanied by clonic jerking or more complex motor behavior, as well as signs of encephalopathy such as diffuse hypotonia, limb spasticity, lack of visual fixation and tracking and mild to moderate intellectual deficiency. The severity can range from controlled to intractable seizures and mild/moderate to severe intellectual disability.	Rare genetic neurological disorder
Orphanet:439822	PDE4D haploinsufficiency syndrome	PDE4D	1	PDE4D haploinsufficiency syndrome is a rare syndromic intellectual disability characterized by developmental delay, intellectual disability, low body mass index, long arms, fingers and toes, prominent nose and small chin.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:439854	Fatal congenital hypertrophic cardiomyopathy due to glycogen storage disease	PRKAG2	1	NA	Rare inborn errors of metabolism;Rare genetic cardiac disease
Orphanet:439897	Lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome	KIF14	1	Lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome is a rare, genetic developmental defect during embryogenesis malformation syndrome characterized by intrauterine growth restriction, flexion arthrogryposis of all joints, severe microcephaly, renal cystic dysplasia/agenesis/hypoplasia and complex malformations of the brain (cerebral and cerebellar hypoplasia, vermis, corpus callosum and/or occipital lobe agenesis, with or without arhinencephaly), as well as of the genitourinary tract (ureteral agenesis/hypoplasia, uterine hypoplasia and/or vaginal atresia), leading to fetal demise.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Ciliopathy;Rare genetic urogenital disease;Rare genetic neurological disorder
Orphanet:440402	Interstitial lung disease due to ABCA3 deficiency	ABCA3	1	Interstitial lung disease due to ABCA3 deficiency is a rare genetic respiratory disease characterized by a variable clinical outcome ranging from a fatal respiratory distress syndrome in the neonatal period to chronic interstitial lung disease developing in infancy or childhood with chronic cough, rapid breathing, shortness of breath and recurrent pulmonary infections. Clinical manifestations of respiratory failure include grunting, intercostal retractions, nasal flaring, cyanosis, and progressive dyspnea.	Rare genetic respiratory disease
Orphanet:440354	Autosomal dominant myopia-midfacial retrusion-sensorineural hearing loss-rhizomelic dysplasia syndrome	COL11A1	1	NA	Genetic otorhinolaryngologic disease;Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:440392	Interstitial lung disease due to SP-C deficiency	SFTPC	1	NA	Rare genetic respiratory disease
Orphanet:440713	Isolated sedoheptulokinase deficiency	SHPK	1	A rare, hereditary disorder of pentose phosphate metabolism characterized by increased urine levels of sedoheptulose and erythtirol, and low-to-normal excretion of sedoheptulose-7P. Clinical presentation of this disorder is currently unclear.	Rare inborn errors of metabolism
Orphanet:440731	L-ferritin deficiency	FTL;FTL	2	NA	
Orphanet:440427	Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency	MARS	1	A rare, genetic interstitial lung disease characterized by accumulation of lipoproteins in the pulmonary alveoli leading to restrictive lung disease and respiratory failure. Patients present with dyspnea, tachypnea, cough, failure to thrive, and digital clubbing. Liver disease have been described in some cases including hepatomegaly, steatosis, fibrosis or cirrhosis.	Rare genetic respiratory disease;Rare genetic hepatic disease
Orphanet:440437	Familial colorectal cancer Type X	BMPR1A;SEMA4A;RPS20	3	A rare, hereditary nonpolyposis colon cancer defined in individuals meeting the Amsterdam criteria for Lynch syndrome, but lacking germline mutations in the mismatch repair genes. It is characterized by a later onset, preferential involvement of distal colon and rectum, lower risk of developing extracolonic cancer, a higher adenoma/carcinoma ratio, a higher differentiation of tumor cells, a more heterogeneous tumor architecture and an infiltrative growth pattern, when compared to Lynch syndrome cases.	Rare genetic tumor;Inherited cancer-predisposing syndrome
Orphanet:440706	Ribose-5-P isomerase deficiency	RPIA	1	Ribose-5-P isomerase deficiency is an extremely rare, hereditary, disorder of pentose phosphate metabolism characterized by progressive leukoencephalopathy and a highly increased ribitol and D-arabitol levels in the brain and body fluids. Clinical presentation includes psychomotor delay, epilepsy, and childhood-onset slow neurological regression with ataxia, spasticity, optic atrophy and sensorimotor neuropathy.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:441447	Early-onset posterior subcapsular cataract	LEMD2;CRYBB2;CHMP4B;EPHA2;UNC45B	5	NA	NA
Orphanet:441452	Early-onset lamellar cataract	BFSP2;CRYAA;CRYAB;CRYBA1;CRYBA4;CRYGC;CRYGD;HSF4;MIP;CRYGS;CRYGB	11	NA	NA
Orphanet:443057	Sporadic porphyria cutanea tarda	HFE	1	NA	Rare genetic skin disease;Rare genetic renal disease;Rare inborn errors of metabolism
Orphanet:443062	Familial porphyria cutanea tarda	UROD;HFE	2	NA	Rare genetic skin disease;Rare genetic renal disease;Rare inborn errors of metabolism
Orphanet:443073	Charcot-Marie-Tooth disease type 2S	IGHMBP2	1	A rare subtype of axonal hereditary motor and sensory neuropathy characterized by progressive distal muscle weakness and atrophy of both the lower and upper limbs, absent or reduced deep tendon reflexes, mild sensory loss, foot drop, and pes cavus leading eventually to wheelchair dependance. Some patients present with early hypotonia and delayed motor development. Scoliosis and variable autonomic disturbances may be associated.	Rare genetic neurological disorder
Orphanet:442835	Undetermined early-onset epileptic encephalopathy	YWHAG;UBA5;GRIN2D;TRAK1;SLC1A2;AP3B2;ATP6V1A;SCN3A;GABRB2;CLTC;NUS1;CYFIP2;NTRK2;FGF12;SZT2;DHDDS;PPP3CA;SYNJ1;STXBP1;SYNGAP1;WWOX;AARS;SCN8A;NECAP1;HCN1;SLC13A5;KCNB1;DNM1;KCNA2;KCNA2;EEF1A2;CNKSR2;CACNA1A;ARV1	34	NA	Rare genetic neurological disorder
Orphanet:443197	X-linked erythropoietic protoporphyria	ALAS2	1	NA	Rare genetic skin disease;Rare genetic renal disease;Rare inborn errors of metabolism
Orphanet:298	Mitochondrial neurogastrointestinal encephalomyopathy	POLG;TYMP;RRM2B	3	Mitochondrial NeuroGastroIntestinal Encephalomyopathy (MNGIE) syndrome is characterized by the association of gastrointestinal dysmotility, peripheral neuropathy, chronic progressive external ophthalmoplegia and leukoencephalopathy.	Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic gastroenterological disease
Orphanet:552	MODY	ABCC8;CEL;GCK;HNF4A;KCNJ11;KLF11;NEUROD1;PDX1;HNF1A;INS;PAX4;BLK;APPL1	13	MODY (maturity-onset diabetes of the young) is a rare, familial, clinically and genetically heterogeneous form of diabetes characterized by young age of onset (generally 10-45 years of age) with maintenance of endogenous insulin production, lack of pancreatic beta-cell autoimmunity, absence of obesity and insulin resistance and extra-pancreatic manifestations in some subtypes.	Rare genetic endocrine disease
Orphanet:443236	Postural orthostatic tachycardia syndrome due to NET deficiency	SLC6A2	1	A rare, genetic, primary orthostatic disorder characterized by dizziness, palpitations, fatigue, blurred vision and tachycardia following postural change from a supine to an upright position, in the absence of hypotension. A syncope with transient cognitive impairment and dyspnea may also occur. The norepinephrine transporter deficiency leads to abnormal uptake and high plasma concentrations of norepinephrine.	Rare genetic neurological disorder
Orphanet:443087	46,XY disorder of sex development due to testicular 17,20-desmolase deficiency	AKR1C2;AKR1C4	2	NA	Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease
Orphanet:443167	NUT midline carcinoma	NUTM1;BRD4	2	NA	
Orphanet:130	Brugada syndrome	SCN1B;SCN5A;CACNA1C;CACNB2;HCN4;KCNE3;TRPM4;TRPM4;GPD1L;SCN3B;KCNJ8;CACNA2D1;KCND3;SCN10A;SLMAP;AKAP9;CALM2;KCNE5;RANGRF;PKP2;SCN2B;ABCC9	22	Brugada syndrome (BrS) manifests with ST segment elevation in right precordial leads (V1 to V3), incomplete or complete right bundle branch block, and susceptibility to ventricular tachyarrhythmia and sudden death. BrS is an electrical disorder without overt myocardial abnormalities.	Rare genetic cardiac disease
Orphanet:277	Severe combined immunodeficiency due to adenosine deaminase deficiency	ADA	1	Severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency is a form of SCID characterized by profound lymphopenia and very low immunoglobulin levels of all isotypes resulting in severe and recurrent opportunistic infections.	Rare inborn errors of metabolism;Rare genetic immune disease
Orphanet:443162	NDE1-related microhydranencephaly	NDE1	1	NDE1-related microhydranencephaly is a rare, hereditary syndrome with a central nervous system malformation as major feature characterized by extreme microcephaly and growth restriction, severe motor delay and mental retardation, and typical radiological findings of gross dilation of the ventricles resulting from the absence (or severe delay in the development) of cerebral hemispheres, hypoplasia of the corpus callosum, cerebellum, and brainstem. Associated features are thin bones and scalp rugae.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:443811	PGM3-CDG	PGM3	1	 gene and characterized by neonatal to childhood onset of recurrent bacterial and viral infections, inflammatory skin diseases, atopic dermatitis and atopic diatheses, and marked serum IgE elevation. Early neurologic impairment is evident including developmental delay, intellectual disability, ataxia, dysarthria, sensorineural hearing loss, myoclonus and seizures.	Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic immune disease
Orphanet:443950	DNAJB2-related Charcot-Marie-Tooth disease type 2	DNAJB2	1	NA	Rare genetic neurological disorder
Orphanet:443988	Ventriculomegaly-cystic kidney disease	CRB2	1	NA	Rare genetic renal disease
Orphanet:444092	Autoimmune interstitial lung disease-arthritis syndrome	COPA	1	NA	Rare genetic respiratory disease
Orphanet:444099	Autosomal dominant spastic paraplegia type 73	CPT1C	1	A pure form of hereditary spastic paraplegia characterized by adult onset of crural spastic paraparesis, hyperreflexia, extensor plantar responses, proximal muscle weakness, mild muscle atrophy, decreased vibration sensation at ankles, and mild urinary dysfunction. Foot deformities have been reported to eventually occur in some patients. No abnormalities are noted on brain magnetic resonance imaging and peripheral nerve conduction velocity studies.	Rare genetic neurological disorder
Orphanet:444138	Peeling skin-leukonychia-acral punctate keratoses-cheilitis-knuckle pads syndrome	CAST	1	NA	Rare genetic skin disease
Orphanet:443995	Mandibulofacial dysostosis with alopecia	EDNRA	1	NA	Genetic otorhinolaryngologic disease;Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:444048	46,XX ovarian dysgenesis-short stature syndrome	MCM9	1	A rare, genetic disorder of sex development characterized by primary amenorrhea, short stature, delayed bone age, decreased levels of estradiol, elevated levels of follicle-stimulating hormone and luteinizing hormone, absent or underdeveloped uterus and ovaries, delayed development of pubic and axillary hair, and normal 46,XX karyotype.	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Genetic infertility
Orphanet:444013	Combined oxidative phosphorylation defect type 23	GTPBP3	1	NA	Rare genetic neurological disorder;Rare genetic cardiac disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:444069	Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome	CENPF	1	NA	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Ciliopathy;Rare genetic neurological disorder
Orphanet:444077	Cognitive impairment-coarse facies-heart defects-obesity-pulmonary involvement-short stature-skeletal dysplasia syndrome	AFF4	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease;Rare genetic cardiac disease;Rare genetic bone disease
Orphanet:444072	Cerebellar-facial-dental syndrome	BRF1	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic odontologic disease
Orphanet:444463	Autoimmune hemolytic anemia-autoimmune thrombocytopenia-primary immunodeficiency syndrome	TPP2	1	NA	Rare genetic immune disease
Orphanet:444490	Familial chylomicronemia syndrome	GPIHBP1;LMF1	2	NA	Rare inborn errors of metabolism;Rare genetic endocrine disease
Orphanet:444458	Combined oxidative phosphorylation defect type 24	NARS2	1	Combined oxidative phosphorylation defect type 24 is a rare mitochondrial oxidative phosphorylation disorder characterized by variable phenotype, including developmental delay with psychomotor regression, intellectual disability, epilepsy, Leigh syndrome, non-syndromic hearing loss, visual impairment and severe myopathy. Decreased activity of mitochondrial respiratory complexes and lactic acidosis are common findings, and diffuse cerebral atrophy may be associated.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:445110	Limb-girdle muscular dystrophy due to POMK deficiency	POMK	1	Limb-girdle muscular dystrophy due to POMK deficiency is a form of limb-girdle muscular dystrophy presenting in infancy with muscle weakness and delayed motor development (eventually learning to walk at 18 months of age) followed by progressive proximal weakness, pseudohypertrophy of calf muscles, mild facial weakness, and borderline intelligence.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:445062	Juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome	DNAJC3	1	NA	Genetic otorhinolaryngologic disease;Rare genetic endocrine disease;Rare genetic neurological disorder
Orphanet:445038	3-methylglutaconic aciduria type 7	CLPB	1	NA	Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:445018	Combined immunodeficiency due to LRBA deficiency	LRBA	1	A rare, genetic, primary immunodeficiency characterized by early onset of recurrent respiratory infections and variable combination of autoimmune disorders, including hemolytic anemia, thrombocytopenic purpura, lymphoproliferative disease, inflammatory bowel disease, colitis, diabetes, arthritis, and dermatitis. Failure to thrive, hepatosplenomegaly and endocrine abnormalities have also been associated. Variable immunologic findings include deficiency of CD4+ T regulatory cells, decreased B-cells, and hypogammaglobulinemia.	Rare genetic immune disease;Rare genetic gastroenterological disease;Rare genetic endocrine disease
Orphanet:447731	NIK deficiency	MAP3K14	1	A rare, genetic, primary combined T and B cell immunodeficiency characterized by recurrent, severe viral and bacterial infections. Immunologic findings include decreased immunoglobulin levels, decreased numbers of B and NK cells, reduced relative CD19+ B cells in peripheral blood, impaired memory responses to viral infections and defective antigen-specific T-cell proliferation.	Rare genetic immune disease
Orphanet:447737	DOCK2 deficiency	DOCK2	1	A rare, primary combined T and B cell immunodeficiency characterized by early-onset of recurrent, invasive viral and bacterial infections associated with T and B cell lymphopenia, functional defects in T and B cells, poor antibody response and thrombocytopenia. Depending on the type of infectious agent, variable clinical manifestations commonly include recurrent pneumonia, bronchiolitis, otitis media, meningoencephalitis, colitis, and diarrhea, leading to fatal multiorgan failure in severe cases.	Rare genetic immune disease
Orphanet:447740	Susceptibility to localized juvenile periodontitis	FPR1	1	NA	Rare genetic immune disease
Orphanet:447877	Polymerase proofreading-related adenomatous polyposis	POLE;POLD1	2	NA	Rare genetic gastroenterological disease;Inherited cancer-predisposing syndrome;Rare genetic tumor
Orphanet:447896	Tremor-ataxia-central hypomyelination syndrome	POLR3A	1	NA	Rare genetic eye disease;Rare genetic neurological disorder
Orphanet:447893	Hypomyelination-cerebellar atrophy-hypoplasia of the corpus callosum syndrome	POLR3A	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:447792	Hemochromatosis type 5	BMP6	1	NA	Rare genetic hepatic disease;Rare inborn errors of metabolism
Orphanet:447795	Lipoyl transferase 2 deficiency	LIPT2	1	NA	
Orphanet:447784	Mitochondrial pyruvate carrier deficiency	MPC1	1	NA	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:447757	Autosomal dominant spastic paraplegia type 9B	ALDH18A1	1	NA	Rare genetic neurological disorder
Orphanet:447753	Autosomal dominant spastic paraplegia type 9A	ALDH18A1	1	NA	Rare genetic eye disease;Rare genetic neurological disorder
Orphanet:447760	Autosomal recessive spastic paraplegia type 9B	ALDH18A1	1	NA	Rare genetic neurological disorder
Orphanet:413667	NA	CYP2C19;CYP2D6	2	NA	NA
Orphanet:413674	NA	CYP2C9;CYP4F2;VKORC1	3	NA	NA
Orphanet:413681	NA	CYP2C9	1	NA	NA
Orphanet:413684	NA	VKORC1	1	NA	NA
Orphanet:413687	NA	NUDT15;TPMT	2	NA	NA
Orphanet:413690	OBSOLETE: Methotrexate toxicity or dose selection	MTHFR;SLC19A1;GGH	3	NA	NA
Orphanet:413693	NA	BCHE	1	NA	NA
Orphanet:413696	NA	SLCO1B1	1	NA	NA
Orphanet:412066	PRKAR1B-related neurodegenerative dementia with intermediate filaments	PRKAR1B	1	PRKAR1B-related neurodegenerative dementia with intermediate filaments is a rare, genetic neurodegenerative disease characterized by dementia and mild parkinsonism with poor levodopa response. Presenting clinical manifestations are memory problems, short attention span, disorientation, language impairment, rigidity, bradykinesia, postural instability and behavioral changes, including apathy, anxiety and delusions.	Rare genetic neurological disorder
Orphanet:412057	Autosomal recessive cerebellar ataxia due to STUB1 deficiency	STUB1	1	A rare hereditary ataxia characterized by progressive truncal and limb ataxia resulting in gait instability. Dysarthria, dysphagia, nystagmus, spasticity of the lower limbs, mild peripheral sensory neuropathy, cognitive impairment and accelerated ageing have also been associated.	Rare genetic neurological disorder
Orphanet:412181	Epidermolysis bullosa simplex due to BP230 deficiency	DST	1	Epidermolysis bullosa simplex due to BP230 deficiency is a rare, hereditary, basal epidermolysis bullosa simplex characterized by mild, predominantly acral, trauma-induced skin fragility, resulting in blisters. Blisters mostly affect the feet, including the dorsal side, and are often several centimetres big.	Rare genetic skin disease
Orphanet:412069	AHDC1-related intellectual disability-obstructive sleep apnea-mild dysmorphism syndrome	AHDC1	1	A rare, syndromic intellectual disability characterized by hypotonia, developmetal delay, absent or severly delayed speech development, intellectual disability, obstructive sleep apnea, mild dysmorphic facial features and behavioral abnormalities. Epilepsy, ataxia and nystagmus have also been reported.	Rare genetic neurological disorder
Orphanet:412189	Epidermolysis bullosa simplex due to exophilin 5 deficiency	EXPH5	1	Epidermolysis bullosa simplex due to exophilin 5 deficiency is a rare, hereditary, basal epidermolysis bullosa simplex characterized by mild, generalized trauma-induced scale crusts and intermittent blistering, sometimes combined with erosions and bleeding, recovering with slight scarring and post-inflammatory hyperpigmentation. Clinical symptoms improve with age.	Rare genetic skin disease
Orphanet:412206	Primary failure of tooth eruption	PTH1R	1	NA	Rare genetic odontologic disease
Orphanet:420179	Malan overgrowth syndrome	NFIX	1	Malan overgrowth syndrome is a multiple congenital anomalies syndrome characterized by moderate postnatal overgrowth, macrocephaly, craniofacial dysmorphism (including high forehead and anterior hairline, downslanting palpebral fissures, prominent chin), developmental delay, and intellectual disability. Additional variable manifestations include unusual behavior, with or without autistic traits, as well as ocular (e.g. strabismus, nystagmus, optic disc pallor/hypoplasia), gastrointestinal (e.g. vomiting, chronic diarrhea, constipation), musculoskeletal (e.g. scoliosis and pectus excavatum), hand/foot (e.g. long, tapered fingers) and central nervous system (e.g. slightly enlarged ventricles) anomalies.	Rare genetic developmental defect during embryogenesis
Orphanet:414750	NA	HLA-A;HLA-B	2	NA	NA
Orphanet:420702	Autosomal recessive severe congenital neutropenia due to CSF3R deficiency	CSF3R	1	 gene. Full maturation of all three lineages in the bone marrow and refractoriness to in vivo rhG-CSF treatment are associated.	Rare genetic immune disease
Orphanet:420728	Combined oxidative phosphorylation defect type 20	VARS2	1	Combined oxidative phosphorylation defect type 20 is a rare mitochondrial oxidative phosphorylation disorder characterized by variable combination of psychomotor delay, hypotonia, muscle weakness, seizures, microcephaly, cardiomyopathy and mild dysmorphic facial features. Variable types of structural brain anomalies have also been reported. Biochemical studies typically show decreased activity of mitochondrial complexes (mainly complex I).	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:420733	Combined oxidative phosphorylation defect type 21	TARS2	1	Combined oxidative phosphorylation defect type 21 is a rare mitochondrial disease characterized by axial hypotonia with limb hypertonia, developmental delay, hyperlactatemia, central nervous system anomalies visible on magnetic resonance imaging (e.g. corpus callosum hypoplasia, lesions of the globus pallidus) and multiple deficiency of the mitochondrial respiratory chain complexes in muscle tissue, but not in fibroblasts or liver.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:420741	RIDDLE syndrome	RNF168	1	A rare, genetic, primary immunodeficiency disorder characterized by increased radiosensitivity(R), mild immunodeficiency (ID), dysmorphic features (D), and learning difficulties (LE).	Rare genetic neurological disorder;Rare genetic immune disease
Orphanet:420492	Adult-onset cervical dystonia, DYT23 type	CIZ1	1	A rare, genetic, isolated dystonia characterized by adult-onset, non-progressive, focal cervical dystonia typically manifesting with torticollis and occasionally accompanied by mild head tremor and essential-type limb tremor.	Rare genetic neurological disorder
Orphanet:420485	Cranio-cervical dystonia with laryngeal and upper-limb involvement	ANO3	1	Cranio-cervical dystonia with laryngeal and upper-limb involvement is a rare genetic, isolated dystonia characterized by a variable combination of cervical dystonia with tremor, blepharospasm, oromandibular and laryngeal dystonia. Dystonia progresses slowly and might spread to become segmental. Arm tremor and myoclonic jerks in the arms or neck have also been reported.	Rare genetic neurological disorder
Orphanet:420429	Glycogen storage disease due to acid maltase deficiency, late-onset	GAA	1	Glycogen storage disease due to acid maltase deficiency, late onset (AMDL), a form of Glycogen storage disease due to acid maltase deficiency (AMD), a degenerative metabolic myopathy particularly affecting respiratory and skeletal muscles, is characterized by an accumulation of glycogen in lysosomes.	Rare genetic cardiac disease;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:420611	Transient myeloproliferative syndrome	GATA1	1	NA	
Orphanet:420584	Postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome	GLI2	1	Postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome is a rare, genetic developmental defect during embryogenesis disorder characterized primarily by congenital hypopituitarism and/or postaxial polydactyly. It can be associated with short stature, delayed bone age, hypogonadotropic hypogonadism, and/or midline facial defects (e.g. hypotelorism, mild midface hypoplasia, flat nasal bridge, and cleft lip and/or palate). Hypoplastic anterior pituitary and ectopic posterior pituitary lobe are frequent findings on MRI examination.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic endocrine disease
Orphanet:420699	Autosomal recessive severe congenital neutropenia due to CXCR2 deficiency	CXCR2	1	.	Rare genetic immune disease
Orphanet:420686	Woolly hair-palmoplantar keratoderma syndrome	KANK2	1	Woolly hair-palmoplantar keratoderma syndrome is a very rare, hereditary epidermal disorder characterized by hypotrichosis/woolly scalp hair, sparse body hair, eyelashes and eyebrows, leukonychia, and striate palmoplantar keratoderma (more severe on the soles than the palms), which progressively worsens with age. Pseudo ainhum of the fifth toes was also reported. Although woolly hair-palmoplantar keratoderma syndrome shares clinical similarities with both Naxos disease and Carvajal syndrome, cardiomyopathy is notably absent.	Rare genetic skin disease
Orphanet:420561	Temple-Baraitser syndrome	KCNH1	1	Temple-Baraitser syndrome is a rare developmental anomalies syndrome characterized by severe intellectual disability and distal hypoplasia of digits, particularly of thumbs and halluces, with nail aplasia or hypoplasia. Facial dysmorphism with a pseudo-myopathic appearance has been reported, which may include high anterior hairline or low frontal hairline with central cowlick, flat forehead, ptosis, hypertelorism, downslanting palpebral fissures, epicanthal folds, ears with thick helices, broad depressed nasal bridge with anteverted nares, short columella, long philtrum, high-arched palate, broad mouth with thick vermilion border of the upper or the lower lip and downturned corners. Marked hypotonia, seizures and global developmental delay have been reported, associated with autistic spectrum disorder manifestations in some patients.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:420573	Severe combined immunodeficiency due to CTPS1 deficiency	CTPS1	1	Severe combined immunodeficiency (SCID) due to CTPS1 deficiency is a rare primary immunodeficiency disorder due to impaired capacity of activated T- and B-cells to proliferate in response to antigen receptor-mediated activation characterized by early-onset, severe, persistent and/or recurrent viral infections due to Epstein-Barr virus (EBV) and Varicella Zoster virus (VZV, including generalized varicella)), as well as recurrent sino-pulmonary bacterial infections due to encapsulated pathogens.	Rare genetic immune disease
Orphanet:420566	Bleeding disorder due to CalDAG-GEFI deficiency	RASGRP2	1	Bleeding disorder due to CalDAG-GEFI deficiency is a rare hematologic disease due to defective platelet function and characterized by mucocutaneous bleeding starting in infancy (around 18 months of age), presenting with prolonged and severe epistaxis, hematomas and bleeding after tooth extraction. Massive menorrhagia and chronic anemia have also been reported.	Rare genetic hematologic disease
Orphanet:423461	Mucolipidosis type III alpha/beta	GNPTAB	1	Mucolipidosis III alpha/beta (MLIII alpha/beta) is a lysosomal disorder characterized by progressive slowing of the growth rate from early childhood, stiffness and pain in joints, gradual coarsening of facial features, moderate developmental delay and mild intellectual disability in most patients.	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:423470	Mucolipidosis type III gamma	GNPTG	1	Mucolipidosis type III gamma (ML 3 gamma) is a very rare lysosomal disease, that has most often been observed in the Middle East, characterized by a progressive slowing of the growth rate in early childhood; stiffness and pain in shoulders, hips, and finger joints; a gradual, mild coarsening of facial features; and by a slower progression, milder clinical course and longer life expectancy than that seen in mucolipidosis type II and mucolipidosis type III alpha/beta. Cognitive function is normal or only slightly impaired and retinitis pigmentosa has been reported in a few patients. Many survive into early adulthood, but ultimately succumb to cardiorespiratory insufficiency.	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:423454	Nail and teeth abnormalities-marginal palmoplantar keratoderma-oral hyperpigmentation syndrome	GRHL2	1	Nail and teeth abnormalities-marginal palmoplantar keratoderma-oral hyperpigmentation syndrome is a rare genetic ectodermal dysplasia syndrome characterized by short stature, nail dystrophy and/or nail loss, oral mucosa and/or tongue hyperpigmentation, dentition abnormalities (delayed teeth eruption, hypodontia, enamel hypoplasia), keratoderma on the margins of the palms and soles and focal hyperkeratosis on the dorsum of the hands and feet. Additionally, dysphagia with esophageal strictures, sensorineural deafness, bronchial asthma and severe iron-deficiency anemia have been observed.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:423384	Autosomal recessive severe congenital neutropenia due to JAGN1 deficiency	JAGN1	1	 gene. Mild facial dysmorphism (i.e. triangular face), short stature, failure to thrive, hypothyroidism, developmental delay, pancreatic insufficiency and coractation of aorta, as well as bone and urogenital abnormalities, may also be associated.	Rare genetic immune disease
Orphanet:423296	Spinocerebellar ataxia type 38	ELOVL5	1	Spinocerebellar ataxia type 38 (SCA38) is a subtype of autosomal dominant cerebellar ataxia type 3 characterized by the adult-onset (average age: 40 years) of truncal ataxia, gait disturbance and gaze-evoked nystagmus. The disease is slowly progressive with dysarthria and limb ataxia following. Additional manifestations include diplopia and axonal neuropathy.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:423306	Microcephaly-short stature-intellectual disability-facial dysmorphism syndrome	QARS	1	Microcephaly-short stature-intellectual disability-facial dysmorphism syndrome is a rare genetic malformation syndrome with short stature characterized by postnatal microcephaly, failure to thrive and short stature, global developmental delay and intellectual disability, hypotonia, dysmorphic features (short nose, depressed nasal bridge, low set ears, short neck, clinodactyly and cutaneous syndactyly of T2-3 at birth and broad forehead, midface retrusion, epicanthal folds, laterally sparse eyebrows, short nose, long philtrum, widely spaced teeth, micrognathia and coarsening of facial features later in life). Other associated features include postnatal transient generalized edema, myopia, strabismus, hypothyroidism.	Rare genetic developmental defect during embryogenesis
Orphanet:423479	X-linked intellectual disability-limb spasticity-retinal dystrophy-diabetes insipidus syndrome	PRPS1	1	#945;-fetoprotein and intrauterine growth restriction is observed in routine pregnancy examination.	Rare inborn errors of metabolism;Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:422526	Hereditary clear cell renal cell carcinoma	OGG1;DIRC2;FLCN;RNF139;FHIT;HSPBAP1;DIRC3	7	Hereditary clear cell renal cell carcinoma (ccRCC) is a hereditary renal cancer syndrome defined as development of ccRCC in two or more family members without evidence of constitutional chromosome 3 translocation, von Hippel-Lindau disease or other tumor predisposing syndromes associated with ccRCC, such as tuberous sclerosis or Birt-Hogg-Dubbé syndrome.	Inherited cancer-predisposing syndrome
Orphanet:423275	Spinocerebellar ataxia type 40	CCDC88C	1	Spinocerebellar ataxia type 40 (SCA40) is a very rare subtype of autosomal dominant cerebellar ataxia type 1, characterized by the adult-onset of unsteady gait and dysarthria, followed by wide-based gait, gait ataxia, ocular dysmetria, intention tremor, scanning speech, hyperreflexia and dysdiadochokinesis.	Rare genetic neurological disorder
Orphanet:424107	Congenital myopathy with myasthenic-like onset	RYR1	1	Congenital myopathy with myasthenic-like onset is a rare, genetic, non-dystrophic myopathy characterized by fatigable muscle weakness associated with congenital myopathy. Patients present with axial hypotonia, myopathic facies with fatigable ptosis, feeding difficulties, delayed gross motor development and proximal limb weakness with a RYR1-related typical pattern of muscle involvement (i.e. severe involvement of the soleus muscle and sparring of the rectus femoris, sartorius, gracilis and semitendinous muscles). Scoliosis and frequent respiratory tract infections are additional observed features.	Rare genetic neurological disorder
Orphanet:424099	Colobomatous microphthalmia-rhizomelic dysplasia syndrome	MAB21L2	1	Colobomatous microphthalmia-rhizomelic dysplasia syndrome is a rare, genetic developmental defect during embryogenesis characterized by a range of developmental eye anomalies (including anophthalmia, microphthalmia, colobomas, microcornea, corectopia, cataract) and symmetric limb rhizomelia with short stature and contractures of large joints. Intellectual disability with autistic features, macrocephaly, dysmorphic features, urogenital anomalies (hypospadia, cryptorchidism), cutaneous syndactyly and precocious puberty may also be present.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease
Orphanet:424261	Autosomal recessive limb-girdle muscular dystrophy type 2Y	TOR1AIP1	1	A form of limb-girdle muscular dystrophy, presenting in the first or second decades of life, characterized by slowly progressive proximal and distal muscle weakness and atrophy. Additional manifestations include contractures of the proximal and distal interphalangeal hand joints, rigid spine, restricted pulmonary function, and mild cardiomyopathy.	Rare genetic neurological disorder
Orphanet:424027	Progressive myoclonic epilepsy type 8	CERS1	1	A rare, genetic, neurological disorder characterized by childhood to adolescent-onset of action myoclonus, generalized tonic-clonic seizures, and slowly progressive, moderate to severe cognitive impairment that may lead to dementia. EEG reveals progressive slowing of background activity and epileptic abnormalities and brain MRI shows cerebellar and brainstem atrophy.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:423894	Microcephaly-complex motor and sensory axonal neuropathy syndrome	VRK1	1	Microcephaly-complex motor and sensory axonal neuropathy syndrome is an extremely rare subtype of hereditary motor and sensory neuropathy characterized by severe, rapidly-progressing, distal, symmetric polyneuropathy and microcephaly (which can be evident in utero) with intact cognition. Clinically it presents with delayed motor development, hypotonia, absent or reduced deep tendon reflexes, progressive muscle wasting and weakness and scoliosis.	Rare genetic neurological disorder
Orphanet:425120	STING-associated vasculopathy with onset in infancy	TMEM173	1	STING-associated vasculopathy with onset in infancy (SAVI) is a rare, genetic autoinflammatory disorder, type I interferonopathy due to constitutive STING (STimulator of INterferon Genes) activation, characterized by neonatal or infantile onset systemic inflammation and small vessel vasculopathy resulting in severe skin, pulmonary and joint lesions. Patients present with intermittent low-grade fever, recurrent cough and failure to thrive, in association with progressive interstitial lung disease, polyarthritis and violaceous scaling lesions on fingers, toes, nose, cheeks, and ears (which are exacerbated by cold exposure) that often progress to chronic acral ulceration, necrosis and autoamputation.	Rare genetic systemic or rheumatologic disease;Rare genetic immune disease
Orphanet:431361	Progressive encephalopathy with leukodystrophy due to DECR deficiency	NADK2	1	Progressive encephalopathy with leukodystrophy due to DECR deficiency is a rare mitochondrial disease, which presents with neonatal hypotonia, central nervous system abnormalities (ventriculomegaly, corpus callosum hypoplasia, cerebellar atrophy), acquired microcephaly, failure to thrive, developmental delay and intermittent lactic acidosis provoked by catabolic stress (e.g. infection). Hyperlysinemia and elevated C10:2 carnitine can be detected in plasma. Later on, epilepsy, cerebellar ataxia, renal tubular acidosis, severe encephalopathy, dystonia, spastic quadriplegia and other complications may develop.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:431272	X-linked scapuloperoneal muscular dystrophy	FHL1	1	A rare, genetic, muscular dystrophy disease characterized by the co-occurrence of late onset scapular and peroneal muscle weakness, principally manifesting with distal lower limb and proximal upper limb weakness and scapular winging.	Rare genetic neurological disorder
Orphanet:431329	Autosomal recessive spastic paraplegia type 57	TFG	1	 gene (3q12.2) encoding protein TFG, which is thought to play a role in ER microtubular architecture and function.	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:431255	Scapuloperoneal spinal muscular atrophy	TRPV4	1	A rare, genetic motor neuron disease characterized by predominantly motor axonal peripheral neuropathy manifesting with progressive scapuloperoneal muscular atrophy and weakness, laryngeal palsy, congenital absence of muscles, and, in some, skeletal abnormalities.	Rare genetic neurological disorder
Orphanet:431149	Combined immunodeficiency due to OX40 deficiency	TNFRSF4	1	Combined immunodeficiency due to OX40 deficiency is a rare combined T and B cell immunodeficiency characterized by susceptibility to develop an aggressive, childhood-onset, disseminated, cutaneous and systemic Kaposi sarcoma.	Rare genetic immune disease
Orphanet:431166	Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection	IFNAR2;STAT2	2	Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection is a rare primary immunodeficiency due to a defect in innate immunity disorder characterized by selective susceptibility to viral infections, particularly after systemic challenge with live viral vaccines, such as the measles, mumps and rubella (MMR) vaccine. Patients present severe, potentially fatal, manifestations to viral illness, including encephalitis, hepatitis and pneumonitis.	Rare genetic immune disease
Orphanet:435438	Progressive myoclonic epilepsy type 7	KCNC1	1	A rare, genetic, neurological disorder characterized by childhood to adolescent onset of progressive myoclonus (which becomes very severe and results in major motor impediment) associated with infrequent tonic-clonic seizures, and, occasionally, ataxia. Learning disability prior to seizure onset and mild cognitive decline may be associated.	Rare genetic neurological disorder
Orphanet:435387	Autosomal dominant Charcot-Marie-Tooth disease type 2Y	VCP	1	A rare, axonal hereditary motor and sensory neuropathy characterized by progressive distal muscle weakness and atrophy of variable onset and severity. Patients present with postural instability, gait and running difficulties, decreased deep tendon reflexes, foot deformities, fine motor impairment, and distal sensory impairment. Dysarthria, dysphagia, and mild cognitive and behavioral abnormalities have also been reported.	Rare genetic neurological disorder
Orphanet:434179	Orofaciodigital syndrome type 14	C2CD3	1	 mutations, characterized by severe microcephaly, trigonocephaly, severe intellectual disability and micropenis, in addition to oral, facial and digital malformations (gingival frenulae, lingual hamartomas, cleft/lobulated tongue, cleft palate, telecanthus, up-slanting palpebral fissures, microretrognathia, postaxial polydactyly of hands and duplication of hallux). Corpus callosum agenesis and vermis hypoplasia with molar tooth sign, on brain imaging, are also associated.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:504523	Severe combined immunodeficiency due to LAT deficiency	LAT	1	NA	Rare genetic immune disease
Orphanet:504530	Combined immunodeficiency due to Moesin deficiency	MSN	1	NA	Rare genetic immune disease
Orphanet:26793	Very long chain acyl-CoA dehydrogenase deficiency	ACADVL	1	Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD) is an inherited disorder of mitochondrial long-chain fatty acid oxidation with a variable presentation including: cardiomyopathy, hypoketotic hypoglycemia, liver disease, exercise intolerance and rhabdomyolysis.	Rare genetic cardiac disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:29072	Hereditary pheochromocytoma-paraganglioma	KIF1B;MDH2;RET;SDHA;SDHB;SDHC;SDHD;FH;SDHAF2;TMEM127;MAX;VHL	12	Hereditary paraganglioma-pheochromocytomas (PGL/PCC) are rare neuroendocrine tumors represented by paragangliomas (occurring in any paraganglia from the skull base to the pelvic floor) and pheochromocytomas (adrenal medullary paragangliomas; see this term).	Rare genetic endocrine disease;Rare genetic tumor;Rare genetic renal disease
Orphanet:28378	Tyrosinemia type 2	TAT	1	Tyrosinemia type 2 is an inborn error of tyrosine metabolism characterized by hypertyrosinemia with oculocutaneous manifestations and, in some cases, intellectual deficit.	Rare inborn errors of metabolism;Rare genetic eye disease;Rare genetic skin disease
Orphanet:29073	Multiple myeloma	CCND1	1	Multiple myeloma (MM) is a malignant tumor of plasma cell characterized by overproduction of abnormal plasma cells in the bone marrow and skeletal destruction. The clinical features are bone pain, renal impairment, immunodeficiency, anemia and presence of abnormal immunoglobulins (Ig).	
Orphanet:30391	Isolated biliary atresia	GPC1	1	Biliary atresia is a rare, progressive obliterative cholangiopathy of the extrahepatic bile ducts, occuring in the embryonic/ perinatal period, leading to severe and persistent jaundice and acholic stool with an unfavorable course in the absence of treatment.	Rare genetic developmental defect during embryogenesis
Orphanet:320	Apparent mineralocorticoid excess	HSD11B2	1	A rare form of pseudohyperaldosteronism characterized by very early-onset and severe hypertension, associated with low renin levels and hypoaldosteronism.	Rare genetic endocrine disease;Rare genetic renal disease
Orphanet:230	Dopamine beta-hydroxylase deficiency	DBH	1	Dopamine beta-hydroxylase deficiency is an extremely rare genetic metabolic disorder characterized by autonomic dysregulation leading mainly to orthostatic hypotension.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:725	Continuous spikes and waves during sleep	GRIN2A;FRRS1L	2	Continuous spikes and waves during sleep (CSWS) is a rare epileptic encephalopathy of childhood characterized by seizures, an electroencephalographic (EEG) pattern of electrical status epilepticus in sleep (ESES) and neurocognitive regression in at least 2 domains of development.	Rare genetic neurological disorder
Orphanet:162	Cataract-glaucoma syndrome	PITX3	1	Cataract-glaucoma syndrome is characterised by the association of total bilateral congenital cataract with the secondary occurrence of glaucoma appearing at ages varying between 10 and 40 years.	Rare genetic eye disease
Orphanet:545	Follicular lymphoma	BCL2;HLA-DRB1;BCL6;IGH	4	Follicular lymphoma is a form of non-Hodgkin lymphoma (see this term) characterized by a proliferation of B cells whose nodular structure of follicular architecture is preserved.	
Orphanet:88	Idiopathic aplastic anemia	PRF1;SBDS;IFNG;TERT;TERC	5	NA	Rare genetic hematologic disease
Orphanet:824	Primary myelofibrosis	JAK2;MPL;TET2;CALR	4	A rare myeloproliferative neoplasm characterized by stem-cell derived clonal over proliferation of mature myeloid lineages, such as erythrocytes, leukocytes, and megakaryocytes, with variable degrees of megakaryocyte atypia, associated with reticulin and/or collagen bone marrow fibrosis, osteosclerosis, ineffective erythropoiesis, angiogenesis, extramedullary hematopoiesis, and abnormal cytokine expression.	Rare genetic hematologic disease
Orphanet:729	Polycythemia vera	JAK2;MPL;TET2	3	Polycythemia vera (PV) is an acquired myeloproliferative disorder characterized by an elevated absolute red blood cell mass caused by uncontrolled red blood cell production, frequently associated with uncontrolled white blood cell and platelet production.	
Orphanet:25980	X-linked myopathy with excessive autophagy	VMA21	1	X-linked myopathy with excessive autophagy is a childhood-onset X-linked myopathy characterised by slow progression of muscle weakness and unique histopathological findings.	Rare genetic neurological disorder
Orphanet:26106	Hereditary diffuse gastric cancer	CDH1;MAP3K6;CTNNA1	3	 genes. In early stages it presents with non-specific and vague symptoms, in advanced stages it may cause nausea and vomiting, dysphagia, loss of appetite, abdominal mass or weight loss. Women have an increased risk of lobular breast cancer as well.	Rare genetic tumor;Rare genetic gastroenterological disease
Orphanet:26792	Short chain acyl-CoA dehydrogenase deficiency	ACADS	1	Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is a very rare inborn error of mitochondrial fatty acid oxidation characterized by variable manifestations ranging from asymptomatic individuals (in most cases) to those with failure to thrive, hypotonia, seizures, developmental delay and progressive myopathy.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:266	Autosomal dominant limb-girdle muscular dystrophy type 1A	MYOT	1	A rare subtype of autosomal dominant limb girdle muscular dystrophy characterized by an adult onset of proximal shoulder and hip girdle weakness (that later progresses to include distal weakness), nasal speech and dysarthria. Other frequent findings include tightened heel cords, reduced deep-tendon reflexes and elevated creatine kinase serum levels. Respiratory failure, as well as mild facial weakness and dysphagia, may also be observed.	Rare genetic neurological disorder
Orphanet:264	Autosomal dominant limb-girdle muscular dystrophy type 1B	LMNA	1	NA	Rare genetic cardiac disease;Rare genetic neurological disorder;Laminopathy
Orphanet:353	Autosomal recessive limb-girdle muscular dystrophy type 2C	SGCG	1	A subtype of autosomal recessive limb-girdle muscular dystrophy characterized by a childhood onset of progressive shoulder and pelvic girdle muscle weakness and atrophy frequently associated with calf hypertrophy, diaphragmatic weakness, and/or variable cardiac abnormalities. Mild to moderate elevated serum creatine kinase levels and positive Gowers sign are reported.	Rare genetic cardiac disease;Rare genetic neurological disorder
Orphanet:219	Autosomal recessive limb-girdle muscular dystrophy type 2F	SGCD	1	A subtype of autosomal recessive limb-girdle muscular dystrophy characterized by a variable age of onset of progressive weakness and wasting of the proximal skeletal muscles of the shoulder and pelvic girdles, frequently associated with progressive respiratory muscle impairment and cardiomyopathy. Calf hypertrophy, muscle cramps and elevated serum creatine kinase levels are also observed. Neuropsychomotor development is usually normal.	Rare genetic cardiac disease;Rare genetic neurological disorder
Orphanet:119	Autosomal recessive limb-girdle muscular dystrophy type 2E	SGCB	1	A subtype of autosomal recessive limb girdle muscular dystrophy characterized by a childhood to adolescent onset of progressive pelvic- and shoulder-girdle muscle weakness, particularly affecting the pelvic girdle (adductors and flexors of hip). Usually the knees are the earliest and most affected muscles. In advanced stages, involvement of the shoulder girdle (resulting in scapular winging) and the distal muscle groups are observed. Calf hypertrophy, cardiomyopathy, respiratory impairment, tendon contractures, scoliosis, and exercise-induced myoglobinuria may be observed.	Rare genetic cardiac disease;Rare genetic neurological disorder
Orphanet:603	Distal myopathy, Welander type	TIA1	1	Distal myopathy, Welander type (WDM) is a distal myopathy characterized by weakness in the distal upper extremities, usually finger and wrist extensors which later progresses to all hand muscles and distal lower extremity, primarily in toe and ankle extensors.	Rare genetic neurological disorder
Orphanet:505227	Combined immunodeficiency due to GINS1 deficiency	GINS1	1	NA	Rare genetic immune disease
Orphanet:588	Muscle-eye-brain disease	LARGE1;POMGNT1;POMT1;POMT2;FKTN;FKRP;B3GALNT2;GMPPB	8	A rare, congenital muscular dystrophy due to dystroglycanopathy characterized by early onset muscular dystrophy, severe muscular hypotonia, severe mental retardation and typical brain and eye malformations, including pachygyria, polymicrogyria, agyria, brainstem and cerebellar structural anomalies, severe myopia, glaucoma, optic nerve and retinal hypoplasia. Patients may present with seizures, macrocephaly or microcephaly, microphthalmia, and congenital contractures. Depending on the severity, limited motor function is acquired. Less severe cases have been reported.	Rare genetic eye disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:505237	Early-onset seizures-distal limb anomalies-facial dysmorphism-global developmental delay syndrome	OTUD6B	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:899	Walker-Warburg syndrome	POMGNT1;POMT1;POMT2;COL4A1;FKTN;FKRP;LARGE1;DAG1;ISPD;POMGNT2;RXYLT1;B3GALNT2;B4GAT1;POMK	14	Walker-Warburg Syndrome (WWS) is a rare form of congenital muscular dystrophy associated with brain and eye abnormalities.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:505216	3-methylglutaconic aciduria type 9	TIMM50	1	NA	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:272	Congenital muscular dystrophy, Fukuyama type	FKTN	1	Fukuyama type muscular dystrophy (FCMD) is a congenital progressive muscular dystrophy characterized by brain malformation (cobblestone lissencephaly), dystrophic changes in skeletal muscle, severe intellectual deficit, epilepsy and motor impairment.	Rare genetic eye disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:505208	3-methylglutaconic aciduria type 8	HTRA2	1	NA	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:265	Autosomal dominant limb-girdle muscular dystrophy type 1C	CAV3	1	NA	Rare genetic neurological disorder
Orphanet:268	Autosomal recessive limb-girdle muscular dystrophy type 2B	DYSF	1	A subtype of autosomal recessive limb-girdle muscular dystrophy characterized by an onset in late adolescence or early adulthood of slowly progressive, proximal weakness and atrophy of shoulder and pelvic girdle muscles. Cardiac and respiratory muscles are not involved. Hypertrophy of the calf muscles and highly elevated serum creatine kinase levels are frequently observed.	Rare genetic neurological disorder
Orphanet:505248	Mucopolysaccharidosis-like syndrome with congenital heart defects and hematopoietic disorders	VPS33A	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:600	Vocal cord and pharyngeal distal myopathy	MATR3	1	Vocal cord and pharyngeal distal myopathy (VCPDM) is a rare autosomal dominant distal myopathy characterized by adult onset of muscle weakness in the feet and hands (slowly progressing to involve proximal limb muscles) combined with vocal or swallowing dysfunction and frequent respiratory muscle involvement in later stages. Normal to mildly elevated creatine kinase (CK) serum levels and rimmed-vacuolated dystrophic muscle fiber changes are associated laboratory and pathologic findings.	Rare genetic neurological disorder
Orphanet:609	Tibial muscular dystrophy	TTN	1	Tibial muscular dystrophy (TMD) is a distal myopathy characterized by weakness of the muscles of the anterior compartment of lower limbs, appearing in the fourth to seventh decade of life.	Rare genetic neurological disorder
Orphanet:602	GNE myopathy	GNE	1	GNE myopathy is a rare autosomal recessive distal myopathy characterized by early adult-onset, slowly to moderately progressive distal muscle weakness that preferentially affects the tibialis anterior muscle and that usually spares the quadriceps femoris. Muscle biopsy reveals presence of rimmed vacuoles.	Rare inborn errors of metabolism;Rare genetic hematologic disease;Rare genetic neurological disorder
Orphanet:505242	Psychomotor regression-oculomotor apraxia-movement disorder-nephropathy syndrome	SLC30A9	1	NA	Rare genetic neurological disorder;Rare genetic renal disease;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:508093	MEPAN syndrome	MECR	1	NA	Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:508533	Skeletal dysplasia-T-cell immunodeficiency-developmental delay syndrome	EXTL3	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic immune disease
Orphanet:508542	Congenital progressive bone marrow failure-B-cell immunodeficiency-skeletal dysplasia syndrome	MYSM1	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic immune disease
Orphanet:508512	Congenital multiple café-au-lait macules-increased sister chromatid exchange syndrome	RMI2;TOP3A	2	NA	Rare genetic skin disease
Orphanet:508529	Generalized basal epidermolysis bullosa simplex with skin atrophy, scarring and hair loss	KLHL24	1	NA	Rare genetic skin disease
Orphanet:508523	Hyperphenylalaninemia due to DNAJC12 deficiency	DNAJC12	1	NA	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:508488	8q24.3 microdeletion syndrome	PUF60	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic renal disease;Rare genetic cardiac disease;Rare chromosomal anomaly
Orphanet:508476	Cleft lip and palate-craniofacial dysmorphism-congenital heart defect-hearing loss syndrome	HYAL2	1	NA	Genetic otorhinolaryngologic disease;Rare genetic developmental defect during embryogenesis;Rare genetic cardiac disease
Orphanet:508501	Oral-facial-digital syndrome with short stature and brachymesophalangy	IFT57	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:508498	Intellectual disability-cardiac anomalies-short stature-joint laxity syndrome	PUF60	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic cardiac disease
Orphanet:505652	CDKL5-related epileptic encephalopathy	CDKL5	1	A rare genetic neurodevelopmental disorder characterized by early-onset drug-resistant seizures and severe neurodevelopmental impairment with major motor development delay.	Rare genetic neurological disorder
Orphanet:506334	Familial steroid-resistant nephrotic syndrome with adrenal insufficiency	SGPL1	1	NA	Rare genetic endocrine disease;Rare genetic renal disease;Rare inborn errors of metabolism
Orphanet:506307	Stromme syndrome	CENPF	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Ciliopathy;Rare genetic eye disease
Orphanet:506358	Gabriele-de Vries syndrome	YY1	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:506353	Autosomal recessive complex spastic paraplegia due to Kennedy pathway dysfunction	SELENOI	1	NA	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:495274	Charcot-Marie-Tooth disease type 2T	MME	1	NA	Rare genetic neurological disorder
Orphanet:495844	C11ORF73-related autosomal recessive hypomyelinating leukodystrophy	HIKESHI	1	NA	Rare genetic eye disease;Rare genetic neurological disorder
Orphanet:495818	9q33.3q34.11 microdeletion syndrome	LMX1B;STXBP1	2	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic skin disease;Rare chromosomal anomaly
Orphanet:496641	Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome	TBCD	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:496686	Kyphosis-lateral tongue atrophy-myofibrillar myopathy syndrome	KY	1	NA	Rare genetic neurological disorder
Orphanet:496689	Kyphoscoliosis-lateral tongue atrophy-hereditary spastic paraplegia syndrome	KY	1	NA	Rare genetic neurological disorder
Orphanet:496751	EVEN-plus syndrome	HSPA9	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:496756	Early-onset progressive encephalopathy-spastic ataxia-distal spinal muscular atrophy syndrome	TBCE	1	NA	Rare genetic neurological disorder
Orphanet:496790	Ocular anomalies-axonal neuropathy-developmental delay syndrome	ATAD3A	1	NA	Rare genetic neurological disorder;Rare genetic cardiac disease;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:494433	MIRAGE syndrome	SAMD9	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease
Orphanet:494439	Retinitis pigmentosa-hearing loss-premature aging-short stature-facial dysmorphism syndrome	EXOSC2	1	NA	Genetic otorhinolaryngologic disease;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:494444	DIAPH1-related sensorineural hearing loss-thrombocytopenia syndrome	DIAPH1	1	NA	Genetic otorhinolaryngologic disease;Rare genetic hematologic disease
Orphanet:494344	RERE-related neurodevelopmental syndrome	RERE	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:494348	Early-onset familial noncirrhotic portal hypertension	DGUOK	1	NA	
Orphanet:494547	Squamous cell carcinoma of the hypopharynx	TNFRSF10B;PTEN;ING1	3	NA	
Orphanet:494541	Childhood-onset benign chorea with striatal involvement	PDE10A	1	NA	Rare genetic neurological disorder
Orphanet:494526	Infantile-onset generalized dyskinesia with orofacial involvement	PDE10A	1	NA	Rare genetic neurological disorder
Orphanet:494550	Squamous cell carcinoma of the larynx	TNFRSF10B;PTEN;ING1	3	NA	
Orphanet:500180	Childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder	UBTF	1	NA	Rare genetic neurological disorder
Orphanet:500188	X-linked external auditory canal atresia-dilated internal auditory canal-facial dysmorphism syndrome	GPRASP2	1	NA	Rare genetic developmental defect during embryogenesis;Genetic otorhinolaryngologic disease
Orphanet:500150	Brain malformations-musculoskeletal abnormalities-facial dysmorphism-intellectual disability syndrome	SON	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:500159	Microcephaly-corpus callosum and cerebellar vermis hypoplasia-facial dysmorphism-intellectual disability syndrom	RAC1	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:302	Epidermodysplasia verruciformis	TMC6;TMC8	2	Epidermodysplasia verruciformis (EV) is a rare inherited genodermatosis characterized by chronic infection with human papillomavirus (HPV) leading to polymorphous cutaneous lesions and high risk of developing non melanoma skin cancer.	Rare genetic skin disease;Rare genetic immune disease
Orphanet:500166	SIN3A-related intellectual disability syndrome due to a point mutation	SIN3A	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:500135	Multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome	CEP55	1	NA	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Ciliopathy;Rare genetic urogenital disease;Rare genetic neurological disorder
Orphanet:500144	Early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome	TRAPPC12	1	NA	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:500055	16p13.2 microdeletion syndrome	USP7	1	NA	Rare genetic neurological disorder;Rare chromosomal anomaly
Orphanet:500095	Tall stature-intellectual disability-renal anomalies syndrome	FIBP	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic renal disease
Orphanet:500062	Infantile-onset periodic fever-panniculitis-dermatosis syndrome	OTULIN	1	NA	Rare genetic systemic or rheumatologic disease
Orphanet:123	Björnstad syndrome	BCS1L	1	Björnstad syndrome is characterized by congenital sensorineural hearing loss and pili torti.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic skin disease
Orphanet:898	Wagner disease	VCAN	1	Wagner disease is a rare hereditary vitreoretinopathy characterized by an anomaleous vitreous associated with myopia, cataract, chorioretinal atrophy, and peripheral tractional or rhegmatogenous retinal detachment.	Rare genetic eye disease
Orphanet:500478	Squamous cell carcinoma of the oropharynx	TNFRSF10B;PTEN;ING1	3	NA	
Orphanet:500481	Squamous cell carcinoma of salivary glands	TNFRSF10B;PTEN;ING1	3	NA	
Orphanet:505	Graham Little-Piccardi-Lassueur syndrome	HLA-DRA	1	A variant of lichen planopilaris characterized by the clinical triad of progressive cicatricial (scarring) alopecia of the scalp, follicular keratotic papules on glabrous skin, and variable alopecia of the axillae and groin.	
Orphanet:500548	Osteosclerotic metaphyseal dysplasia	LRRK1	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:170	Woolly hair	LPAR6;LIPH;KRT74;KRT71;KRT25	5	Woolly hair is a rare congenital abnormality of the structure of the scalp hair marked by extreme kinkiness of the hair.	Rare genetic skin disease
Orphanet:500533	Polyhydramnios-megalencephaly-symptomatic epilepsy syndrome	STRADA	1	NA	Rare genetic neurological disorder
Orphanet:500545	Severe neurodevelopmental disorder with feeding difficulties-stereotypic hand movement-bilateral cataract	NACC1	1	NA	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:500464	Squamous cell carcinoma of the nasal cavity and paranasal sinuses	TNFRSF10B;PTEN;ING1	3	NA	
Orphanet:520	Acute promyelocytic leukemia	PML;PRKAR1A;RARA;STAT5B;FIP1L1;NPM1;NABP1;ZBTB16;NUMA1;TBL1XR1	10	An aggressive form of acute myeloid leukemia (AML), characterized by arrest of leukocyte differentiation at the promyelocyte stage, due to a specific chromosomal translocation t(15;17) in myeloid cells, and manifests with easy bruising, hemorrhagic diathesis and fatigue.	
Orphanet:502363	Squamous cell carcinoma of the oral cavity	TNFRSF10B;PTEN;ING1	3	NA	
Orphanet:502366	Squamous cell carcinoma of the lip	TNFRSF10B;PTEN;ING1	3	NA	
Orphanet:502423	Mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome	MSTO1	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:502430	Metopic ridging-ptosis-facial dysmorphism syndrome	ZNF462	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic bone disease
Orphanet:502434	STAG1-related intellectual disability-facial dysmorphism-gastroesophageal reflux syndrome	STAG1	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:502444	Alkaline ceramidase 3 deficiency	ACER3	1	NA	Rare genetic neurological disorder
Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism	PROK2;PROKR2;CHD7;FGFR1;GNRHR;KISS1R;NSMF;GNRH1;FGF8;TAC3;TACR3;WDR11;HS6ST1;KISS1;FGF17;DUSP6;SPRY4;ANOS1	18	NA	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility
Orphanet:91	Aromatase deficiency	CYP19A1	1	A rare disorder that disrupts the synthesis of estradiol, resulting in hirsutism of mothers during gestation of an affected child; pseudohermaphroditism and virilization in women; and tall stature, osteoporosis and obesity in men.	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease
Orphanet:785	Estrogen resistance syndrome	ESR1	1	Estrogen resistance syndrome is a rare, genetic endocrine disease characterized by estrogen-receptor insensitivity to estrogens and the presence of elevated estrogen and gonadotropin serum levels. Clinical manifestations include absent breast development and primary amenorrhea in association with multicystic ovaries and/or hypoplastic uterus in female patients, normal or abnormal gonadal development in male patients and markedly delayed bone maturation, persistence of open epiphyses, reduced bone mineral density, and variable tall stature in both sexes. Glucose intolerance, hyperinsulinemia and lipid abnormalities may also be present.	Rare genetic gynecological and obstetrical diseases;Genetic infertility
Orphanet:873	Desmoid tumor	CTNNB1;APC	2	A desmoid tumor (DT) is a benign, locally invasive soft tissue tumor associated with a high recurrence rate but with no metastatic potential.	
Orphanet:703	Bullous pemphigoid	HLA-DRB1;HLA-DQB1	2	Bullous pemphigoid (BP) is the most common form of autoimmune bullous dermatosis.	
Orphanet:841	Sebocystomatosis	KRT17	1	Sebocystomatosis is characterized by multiple (100 to 2000) asymptomatic dermal cysts that usually occur on the sternal region, upper back, axillae and proximal parts of the extremities.	Rare genetic skin disease
Orphanet:867	Familial multiple trichoepithelioma	CYLD	1	NA	Rare genetic tumor
Orphanet:497906	Childhood-onset basal ganglia degeneration syndrome	VAC14	1	NA	Rare genetic neurological disorder
Orphanet:735	Porokeratosis of Mibelli	MVK;PMVK	2	Porokeratosis of Mibelli (PM) is a form of porokeratosis that is characterized by the presence of brown single or multiple annular plaques of varying size, that are sometimes confluent, with a distinctive sharply-defined keratotic border.	Rare genetic skin disease
Orphanet:659	Mutilating palmoplantar keratoderma with periorificial keratotic plaques	MBTPS2;TRPV3	2	Mutilating palmoplantar keratoderma (PPK) with periorificial keratotic plaques (also known as Olmsted syndrome) is a hereditary palmoplantar keratoderma characterized by the combination of bilateral mutilating transgredient palmoplantar keratoderma and periorificial keratotic plaques.	Rare genetic skin disease
Orphanet:523	Hereditary leiomyomatosis and renal cell cancer	FH	1	Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a hereditary cancer syndrome characterized by a predisposition to cutaneous and uterine leiomyomas and, in some families, to renal cell cancer.	Rare genetic tumor;Inherited cancer-predisposing syndrome
Orphanet:497757	MME-related autosomal dominant Charcot Marie Tooth disease type 2	MME	1	NA	Rare genetic neurological disorder
Orphanet:530	Lipoid proteinosis	ECM1	1	Lipoid proteinosis (LP) is a rare genodermatosis characterized clinically by mucocutaneous lesions, hoarseness developing in early childhood and, at times, neurological complications.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:497764	Spinocerebellar ataxia type 43	MME	1	Spinocerebellar ataxia type 43 is a rare autosomal dominant cerebellar ataxia type I disorder characterized by late adult-onset of slowly progressive cerebellar ataxia, typically presenting with balance and gait disturbances, in association with axonal peripheral neuropathy resulting in reduced/absent deep tendon reflexes and sensory impairment. Lower limb pain and amyotrophy may be present, as well as various cerebellar signs, including dysarthria, nystagmus, hypometric saccades and tremor.	Rare genetic neurological disorder
Orphanet:734	Alpha delta granule deficiency	GFI1B	1	NA	Rare genetic hematologic disease
Orphanet:721	Gray platelet syndrome	NBEAL2;GFI1B	2	Gray platelet syndrome (GPS) is a rare inherited bleeding disorder characterized by macrothrombocytopenia, myelofibrosis, splenomegaly and typical gray appearance of platelets on Wright stained peripheral blood smear.	Rare genetic hematologic disease
Orphanet:722	Hypoplasminogenemia	PLG	1	Severe hypoplasminogenemia (HPG) or type 1 plasminogen (plg) deficiency is a systemic disease characterised by markedly impaired extracellular fibrinolysis leading to the formation of ligneous (fibrin-rich) pseudomembranes on mucosae during wound healing.	
Orphanet:749	Congenital prekallikrein deficiency	KLKB1	1	NA	Rare genetic hematologic disease
Orphanet:853	Fetal and neonatal alloimmune thrombocytopenia	GP1BA;GP1BB;ITGA2B;ITGB3;ITGA2;CD109	6	Foetal/neonatal alloimmune thrombocytopaenia (NAIT) results from maternal alloimmunisation against foetal platelet antigens inherited from the father and different from those present in the mother, and usually presents as a severe isolated thrombocytopaenia in otherwise healthy newborns.	
Orphanet:498359	Aquagenic palmoplantar keratoderma	CFTR	1	NA	
Orphanet:483	Congenital high-molecular-weight kininogen deficiency	KNG1	1	NA	Rare genetic hematologic disease
Orphanet:852	X-linked thrombocytopenia with normal platelets	WAS	1	NA	Rare genetic hematologic disease
Orphanet:465	Congenital plasminogen activator inhibitor type 1 deficiency	SERPINE1	1	A rare hemorrhagic disorder due to a constitutional haemostatic factors defect characterized by premature lysis of hemostatic clots and a moderate bleeding tendency.	Rare genetic hematologic disease;Serpinopathy
Orphanet:498251	Menstrual cycle-dependent periodic fever	HTR1A	1	NA	
Orphanet:143	Parathyroid carcinoma	CDC73	1	Parathyroid carcinoma (PRTC) is a very rare, slow-growing, clinically serious endocrine tumor that generally develops in mid-adulthood. PRTC presents as a palpable painless mass in the neck and causes severe hypercalcemia and related symptoms, non-specific gastrointestinal manifestations, as well as renal and bone complications related to primary hyperparathyroidism (nephrolithiasis, impaired renal function, osteoporosis, bone pain, and pathologic fractures, etc.). Some PRTCs are however non-functioning tumors.	
Orphanet:786	Generalized glucocorticoid resistance syndrome	NR3C1	1	A rare, adrenogenital syndrome characterized by generalized, partial tissue insensitivity to glucocorticoids leading to variable phenotype, including asymptomatic individuals with only biochemical alterations or patients with ambiguous genitalia at birth in females, hypertension, acne, hirsutism, precocious puberty, male-pattern hair loss, anxiety and depression in both sexes, menstrual irregularities in women, and oligospermia in men.	Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease;Rare genetic gynecological and obstetrical diseases
Orphanet:334	Familial atrial fibrillation	ABCC9;PITX2;SCN5A;GATA4;KCNE1;KCNE2;KCNJ2;KCNQ1;NKX2-5;GJA5;SCN1B;MYL4;NKX2-6;SCN4B;KCNA5;NUP155;NPPA;SCN3B;GATA6;GATA5;SCN2B	21	Familial atrial fibrillation is a rare, genetically heterogenous cardiac disease characterized by erratic activation of the atria with an irregular ventricular response, in various members of a single family. It may be asymptomatic or associated with palpitations, dyspnea and light-headedness. Concomitant rhythm disorders and cardiomyopathies are frequently reported.	Rare genetic cardiac disease
Orphanet:615	Familial atrial myxoma	PRKAR1A	1	Familial atrial myxoma is a rare, genetic cardiac tumor characterized by the presence of a primary, benign, gelatinous mass located in the atria and composed of primitive connective tissue cells and stroma (resembling mesenchyme) in several members of a family. Clinical presentation depends on the size, mobility and location of tumor, ranging from nonspecific and/or constitutional symptoms to sudden cardiac death, and includes dyspnea, hemoptisis, syncope, fatigue, fever, cutaneous rash, increases in venous pressure and/or peripheral edema.	Rare genetic tumor
Orphanet:1330	Partial atrioventricular canal	CRELD1;GATA4;GATA6;NR2F2	4	A congenital heart malformation characterized by an atrial septal defect (ASD; ostium primum), clefts of mitral and occasionally tricuspid valves, two separate atrioventricular (AV) valve annuli and an intact ventricular septum. The typical symptoms of PAVC are impaired exercise capacity and exertional dyspnea.	
Orphanet:498497	Short rib-polydactyly syndrome type 5	WDR35	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:498693	MYBPC1-related autosomal recessive non-lethal arthrogryposis multiplex congenita syndrome	MYBPC1	1	NA	Rare genetic developmental defect during embryogenesis
Orphanet:444	Marie Unna hereditary hypotrichosis	EPS8L3;HR	2	A rare autosomal dominant hair loss disorder characterized by the absence or scarcity of scalp hair, eyebrows, and eyelashes at birth; coarse and wiry hair during childhood; and progressive hair loss beginning around puberty.	Rare genetic skin disease
Orphanet:498481	LRP5-related primary osteoporosis	LRP5;LRP5	2	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:573	Monilethrix	KRT86;KRT83;KRT81;DSG4	4	A rare genodermatosis characterized by a hair shaft dysplasia resulting in hypotrichosis.	Rare genetic skin disease
Orphanet:498494	Mirror-image polydactyly	PITX1	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:384	Huriez syndrome	SMARCAD1	1	NA	Rare genetic skin disease
Orphanet:41	Dyschromatosis symmetrica hereditaria	ADAR	1	A rare genodermatosis characterised by the presence of hyperpigmented and hypopigmented macules, principally located on the extremities and limbs.	Rare genetic skin disease
Orphanet:122	Birt-Hogg-Dubé syndrome	FLCN	1	Birt-Hogg-Dube (BHD) syndrome is characterized by skin lesions, kidney tumors, and pulmonary cysts that may be associated with pneumothorax. It is a rare clinicopathologic condition named after the three Canadian physicians who reported the syndrome in 1977.	Rare genetic tumor;Inherited cancer-predisposing syndrome
Orphanet:241	Dyschromatosis universalis hereditaria	ABCB6	1	A rare, genetic, pigmentation anomaly of the skin characterized by generalized, irregularly shaped, asymptomatic, hyper- and hypopigmented macules distributed in a reticular pattern involving the trunk, limbs, and sometimes the face. The palms, soles and mucosa are usually not affected. Systemic abnormalities have been rarely reported.	Rare genetic skin disease
Orphanet:316	Progressive symmetric erythrokeratodermia	KRT83;KDSR;LOR	3	NA	Rare genetic skin disease
Orphanet:211	Familial cylindromatosis	CYLD	1	NA	Rare genetic tumor
Orphanet:2908	Kindler syndrome	FERMT1	1	Kindler syndrome (KS) is the fourth major type of epidermolysis bullosa (EB), besides simplex, junctional and dystrophic forms, and is characterized by skin fragility and blistering at birth followed by development of photosensitivity and progressive poikilodermatous skin changes.	Rare genetic skin disease
Orphanet:779	Reynolds syndrome	LBR	1	Reynolds syndrome (RS) is an autoimmune disorder characterized by the association of primary biliary cirrhosis (PBC) with limited cutaneous systemic sclerosis (lcSSc) (see these terms).	
Orphanet:486811	Prenatal-onset spinal muscular atrophy with congenital bone fractures	ASCC1;TRIP4	2	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:486815	Congenital muscular dystrophy-respiratory failure-skin abnormalities-joint hyperlaxity syndrome	TRIP4	1	NA	Rare genetic neurological disorder
Orphanet:485418	EMILIN-1-related connective tissue disease	EMILIN1	1	NA	Rare genetic neurological disorder
Orphanet:485421	MFF-related encephalopathy due to mitochondrial and peroxisomal fission defect	MFF	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:485350	CLCN4-related X-linked intellectual disability syndrome	CLCN4	1	NA	Rare genetic neurological disorder
Orphanet:485275	Acquired schizencephaly	EMX2;SIX3;SHH	3	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:482606	X-linked keloid scarring-reduced joint mobility-increased optic cup-to-disc ratio syndrome	FLNA	1	NA	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic skin disease
Orphanet:482601	Adenylosuccinate synthetase-like 1-related distal myopathy	ADSSL1	1	NA	Rare genetic neurological disorder
Orphanet:31837	Pulmonary venoocclusive disease	BMPR2;EIF2AK4	2	NA	Rare genetic respiratory disease
Orphanet:480864	Recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome	TANGO2	1	Recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome is a rare, genetic, neurodegenerative disease characterized by episodic metabolic encephalomyopathic crises (of variable frequency and severity which are frequently precipitated by an acute illness) which manifest with profound muscle weakness, ataxia, seizures, cardiac arrhythmias, rhabdomyolysis with myoglobinuria, elevated plasma creatine kinase, hypoglycemia, lactic acidosis, increased acylcarnitines and a disorientated or comatose state. Global developmental delay, intellectual disability and cortical, pyramidal and cerebellar signs develop with subsequent progressive neurodegeneration causing loss of expressive language and varying degrees of cerebral atrophy.	Rare genetic neurological disorder;Rare genetic cardiac disease
Orphanet:480907	X-linked intellectual disability-global development delay-facial dysmorphism-sacral caudal remnant syndrome	TAF1	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:480898	Global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome	EMC1	1	Global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome is a rare, genetic, neurological disorder characterized by mild to severe developmental delay and speech impairment, truncal hypotonia, abnormalities of vision (including cortical visual impairment and abnormal visual-evoked potentials), progressive brain atrophy mainly affecting the cerebellum, and shortened or atrophic corpus callosum. Other clinical findings may include increased muscle tone in the extremities, dystonic posturing, hyporeflexia, scoliosis, postnatal microcephaly and variable facial dysmorphism (e.g. deep-set eyes, gingival hyperplasia, short philtrum and retrognathia).	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:480880	X-linked female restricted facial dysmorphism-short stature-choanal atresia-intellectual disability	USP9X	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:480556	Isolated neonatal sclerosing cholangitis	DCDC2	1	Isolated neonatal sclerosing cholangitis is a rare, genetic, biliary tract disease characterized by severe neonatal-onset cholangiopathy with patent bile ducts and absence of ichthyosiform skin lesions. Patients present with jaundice, acholic stools, hepatosplenomegaly and high serum gamma-glutamyltransferase activity. Liver histology shows portal fibrosis, ductular proliferation, hepatocellular metallothionein deposits, and intralobular bile-pigment accumulations. Some patients may also have renal disease.	Rare genetic hepatic disease
Orphanet:31709	Infantile convulsions and choreoathetosis	PRRT2;SCN8A	2	Infantile Convulsions and paroxysmal ChoreoAthetosis (ICCA) syndrome is a neurological condition characterized by the occurrence of seizures during the first year of life (Benign familial infantile epilepsy ; see this term) and choreoathetotic dyskinetic attacks during childhood or adolescence.	Rare genetic neurological disorder
Orphanet:480541	High grade B-cell lymphoma with MYC and/ or BCL2 and/or BCL6 rearrangement	MYC;BCL2;BCL6	3	NA	
Orphanet:480851	Hereditary thrombocytopenia with early-onset myelofibrosis	SRC	1	NA	Rare genetic hematologic disease
Orphanet:480682	Autosomal recessive limb-girdle muscular dystrophy type 2Z	POGLUT1	1	NA	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:481665	USP18 deficiency	USP18	1	NA	Rare genetic systemic or rheumatologic disease
Orphanet:482077	HTRA1-related autosomal dominant cerebral small vessel disease	HTRA1	1	NA	Rare genetic neurological disorder
Orphanet:481986	Familial schizencephaly	COL4A1	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:481152	PYCR2-related microcephaly-progressive leukoencephalopathy	PYCR2	1	PYCR2-related microcephaly-progressive leukoencephalopathy is a rare, genetic, syndromic intellectual disability disorder characterized by progressive postnatal microcephaly, cerebral hypomyelination and severe psychomotor developmental delayed with absent speech, as well as axial hypotonia, appendicular hypertonia with hyperextensibility of the wrists and ankles, hyperreflexia, severe muscle wasting and failure to thrive. Associated craniofacial dysmorphism includes triangular facies with bitemporal narrowing, down- or upslanting palpebral fissures, malar hypoplasia, large malformed ears with overfolded helices, upturned bulbous nose, long smooth philtrum and thin vermilion borders.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:481662	Familial Chilblain lupus	SAMHD1;TREX1;TMEM173	3	NA	Rare genetic skin disease;Rare genetic systemic or rheumatologic disease;Rare genetic neurological disorder
Orphanet:480476	Progressive familial intrahepatic cholestasis type 5	NR1H4	1	NA	Rare inborn errors of metabolism;Rare genetic hepatic disease
Orphanet:480491	MYO5B-related progressive familial intrahepatic cholestasis	MYO5B	1	NA	Rare inborn errors of metabolism;Rare genetic hepatic disease
Orphanet:480483	Progressive familial intrahepatic cholestasis type 4	TJP2	1	NA	Rare inborn errors of metabolism;Rare genetic hepatic disease
Orphanet:480528	Lethal hydranencephaly-diaphragmatic hernia syndrome	PLAT	1	Lethal hydranencephaly-diaphragmatic hernia syndrome is a rare, genetic, lethal, multiple congenital anomalies syndrome characterized by hydranencephaly and diaphragmatic hernia, as well as macrocephaly, a widely open anterior fontanel, scaphoid abdomen and hypotonia. Additionally, congenital heart defects, polyhydramnios and pulmonary hypertension have also been associated.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:480536	MSH3-related attenuated familial adenomatous polyposis	MSH3	1	NA	Rare genetic gastroenterological disease;Inherited cancer-predisposing syndrome;Rare genetic tumor
Orphanet:477814	Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome	DIAPH1	1	Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome is a rare, genetic, neuro-ophthalmological syndrome characterized by post-natal, progressive microcephaly and early-onset seizures, associated with delayed global development, bilateral cortical visual impairment and moderate to severe intellectual disability. Additional manifestations include short stature, generalized hypotonia and pulmonary complications, such as recurrent respiratory infections and bronchiectasis. Auditory and metabolic screenings are normal.	Rare genetic eye disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:477787	Cytosolic phospholipase-A2 alpha deficiency associated bleeding disorder	PLA2G4A	1	NA	Rare genetic hematologic disease;Rare genetic gastroenterological disease
Orphanet:478029	Combined oxidative phosphorylation defect type 29	TXN2	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:478042	Combined oxidative phosphorylation defect type 30	TRMT10C	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:477993	Palatal anomalies-widely spaced teeth-facial dysmorphism-developmental delay syndrome	KDM1A	1	Palatal anomalies-widely spaced teeth-facial dysmorphism-developmental delay syndrome is a rare, genetic multiple congenital anomalies/dysmorphic syndrome characterized by global developmental delay, axial hypotonia, palate abnormalities (including cleft palate and/or high and narrow palate), dysmorphic facial features (including prominent forehead, hypertelorism, downslanting palpebral fissures, wide nasal bridge, thin lips and widely spaced teeth), and short stature. Additional manifestations may include digital anomalies (such as brachydactyly, clinodactyly, and hypoplastic toenails), a single palmar crease, lower limb hypertonia, joint hypermobility, as well as ocular and urogenital anomalies.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:477857	Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency	RORC	1	NA	Rare genetic immune disease
Orphanet:477817	PMP22-RAI1 contiguous gene duplication syndrome	RAI1	1	NA	Rare chromosomal anomaly;Rare genetic neurological disorder
Orphanet:477831	Skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome	PDGFRB	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:478049	Lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome	MIPEP	1	Lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome is rare, genetic, neurometabolic disease characterized by global developmental delay, severe hypotonia, seizures, cataracts, cardiomyopathy (including left or bi-ventricular hypertrophy, dilated cardiomyopathy) and left ventricular non-compaction, typically resulting in infantile or early-childhood death. Patients usually present metabolic lactic acidosis, failure to thrive, head lag, respiratory problems and decrease in respiratory chain complex activity. Highly variable cerebral abnormalities have been reported and include microcephaly, prominent extra-axial cerebrospinal fluid spaces, diffuse neuronal loss and cortical/white matter gliosis.	Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:477661	IL21-related infantile inflammatory bowel disease	IL21	1	NA	Rare genetic gastroenterological disease;Rare genetic immune disease
Orphanet:477684	Combined oxidative phosphorylation defect type 26	TRMT5	1	NA	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:477673	Postnatal microcephaly-infantile hypotonia-spastic diplegia-dysarthria-intellectual disability syndrome	GPT2	1	NA	Rare genetic neurological disorder
Orphanet:477738	Pediatric multiple sclerosis	HLA-DQB1;HLA-DRB1	2	Pediatric multiple sclerosis (MS) is a rare multiple sclerosis variant characterized by the onset of multiple sclerosis (i.e. one or multiple episodes of clinical CNS symptoms consistent with acquired CNS demyelination, with radiologically proven dissemination of inflammatory lesions in space and time, following exclusion of other disorders) before the age of 18 years old. Pediatric MS patients present a predominantly relapsing-remitting course with first attack usually consisting of optic neuritis, transverse myelitis, acute disseminated encephalomyelitis and monofocal or polyfocal neurological deficits. A high burden of T2-hyperintense lesions on intial MRI, primarily of the supratentorial region and/or of the cervical spinal cord, has been reported.	
Orphanet:477749	Pontine autosomal dominant microangiopathy with leukoencephalopathy	COL4A1	1	NA	Rare genetic neurological disorder
Orphanet:477742	Nodular fasciitis	USP6;MYH9	2	NA	
Orphanet:477774	Combined oxidative phosphorylation defect type 27	CARS2	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:476119	Autosomal dominant preaxial polydactyly-upperback hypertrichosis syndrome	SHH	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic skin disease
Orphanet:476113	Combined immunodeficiency due to TFRC deficiency	TFRC	1	NA	Rare genetic immune disease
Orphanet:476126	Micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome	TRIO	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:476406	Congenital generalized hypercontractile muscle stiffness syndrome	TPM3	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:476394	PMP2-related Charcot-Marie-Tooth disease type 1	PMP2	1	NA	Rare genetic neurological disorder
Orphanet:493342	Vibratory urticaria	ADGRE2	1	Vibratory urticaria is a rare, genetic urticaria characterized by the development of localized, short-lasting (resolving within 1 hour), pruritic, erythematous, edematous hives in response to repetitive frictional or vibratory stimulation of the skin, which in some cases is accompanied by facial flushing, headache or the sensation of a metallic taste. Concomitant local mast cell degranulation and increased histamine serum levels are additional typical findings.	Rare genetic skin disease
Orphanet:488642	TELO2-related intellectual disability-neurodevelopmental disorder	TELO2	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:488647	DDX41-related hematologic malignancy predisposition syndrome	DDX41	1	NA	
Orphanet:488650	Distal myopathy, Tateyama type	CAV3	1	Distal myopathy, Tateyama type is a rare, genetic, slowly progressive, distal myopathy disorder characterized by muscle atrophy and weakness limited to the small muscles of the hands and feet (in particular, thenar and hypothenar muscle atrophy), increased serum creatine kinase, and severely reduced caveolin-3 expression on muscle biopsy. Some patients may also show calf hypertrophy, pes cavus, and signs of muscle hyperexcitability.	Rare genetic neurological disorder
Orphanet:488618	Transketolase deficiency	TKT	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic cardiac disease;Rare inborn errors of metabolism
Orphanet:488627	Severe growth deficiency-strabismus-extensive dermal melanocytosis-intellectual disability syndrome	PUS3	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:488632	TBCK-related intellectual disability syndrome	TBCK	1	TBCK-related intellectual disability syndrome is a rare, genetic, syndromic intellectual disability characterized by usually profound intellectual disability with absent speech, severe infantile hypotonia with decreased or absent reflexes, markedly slow motor development (with no progress beyond the ability to sit independently), early-onset epilepsy, strabismus and post-natal onset of progressive brain atrophy (incl. loss of brain volume, ex vacuo ventriculomegaly, dysgenesis of corpus callosum, white matter abnormalities ranging from non-specific changes to leukodystrophy). Swallowing difficulties, respiratory insufficiency, osteoporosis and variable craniofacial dysmorphisms (incl. plagio/brachicephaly, bitemporal narrowing, high-arched eyebrows, high nasal bridge, anteverted nares, high palate, tented upper lip) may constitute additional clinical features.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:488635	Early-onset epilepsy-intellectual disability-brain anomalies syndrome	PIGG	1	NA	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:488265	Osteofibrous dysplasia	MET	1	Osteofibrous dysplasia is a rare, genetic primary bone dysplasia characterized by the presence of a benign, fibro-osseous, osteolytic tumor typically located in the tibia (occasionally the fibula, or both) and usually involving the anterior diaphyseal cortex with adjacent cortical expansion. It may on occasion be asymptomatic or may present with a palpable mass, pain, tenderness and/or anterior bowing of the tibia.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:488232	Split-foot malformation-mesoaxial polydactyly syndrome	MAP3K20	1	NA	Genetic otorhinolaryngologic disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic skin disease
Orphanet:488333	Autosomal dominant Charcot-Marie-Tooth disease type 2W	HARS	1	NA	Rare genetic neurological disorder
Orphanet:488437	SIX2-related frontonasal dysplasia	SIX2	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:488613	Global developmental delay-neuro-ophthalmological abnormalities-seizures-intellectual disability syndrome	GNB1	1	NA	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:488594	Autosomal recessive spastic paraplegia type 76	CAPN1	1	Autosomal recessive spastic paraplegia type 76 is a rare, complex hereditary spastic paraplegia characterized by adult onset slowly progressive, mild to moderate lower limb spasticity and hyperreflexia, resulting in gait disturbances, commonly associated with upper limb hyperreflexia and dysarthria. Foot deformities (usually pes cavus) and extensor plantar responses are also frequent. Additional features may include ataxia, lower limb weakness/amyotrophy, abnormal bladder function, distal sensory loss and mild intellectual deterioration.	Rare genetic neurological disorder
Orphanet:488197	Familial progressive retinal dystrophy-iris coloboma-congenital cataract syndrome	MIR204	1	NA	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:488168	Microcephaly-congenital cataract-psoriasiform dermatitis syndrome	MSMO1	1	NA	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic eye disease;Rare genetic skin disease
Orphanet:488191	Female infertility due to oocyte meiotic arrest	WEE2;PATL2;TUBB8	3	NA	Genetic infertility
Orphanet:487796	Macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome	CDC42	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic hematologic disease
Orphanet:487814	Autosomal dominant Charcot-Marie-Tooth disease type 2 due to DGAT2 mutation	DGAT2	1	NA	Rare genetic neurological disorder
Orphanet:487825	Pierpont syndrome	TBL1XR1	1	Pierpont syndrome is a rare subcutaneous tissue disorder characterized by axial hypotonia after birth, prolonged feeding difficulties, moderate to severe global developmental delay, seizures (in particular absence seizures), fetal digital pads, distinctive plantar fat pads anteromedial to the heels, deep palmar and plantar grooves. Additionally, distinct craniofacial dysmorphic features, notably a broad face with high forehead, high anterior hairline, narrow palpebral fissures that take on a crescent moon shape when smiling, broad nasal bridge and tip with anteverted nostrils, mild midfacial hypoplasia, long, smooth philtrum, thin upper lip vermillion, small, widely spaced teeth and flat occiput/microcephaly/brachycephaly, are also chararteristic. Over time, fat pads may become less prominent and disappear.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:31150	Tangier disease	ABCA1	1	Tangier disease (TD) is a rare lipoprotein metabolism disorder characterized biochemically by an almost complete absence of plasma high-density lipoproteins (HDL), and clinically by liver, spleen, lymph node and tonsil enlargement along with peripheral neuropathy in children and adolescents, and, occasionally, cardiovascular disease in adults.	Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic endocrine disease
Orphanet:31043	Familial primary hypomagnesemia with hypercalciuria and nephrocalcinosis without severe ocular involvement	CLDN16	1	Familial primary hypomagnesemia with hypercalciuria and nephrocalcinosis without severe ocular involvement (FHHN) is a form of familial primary hypomagnesemia (FPH; see this term), characterized by recurrent urinary tract infections, nephrolithiasis, bilateral nephrocalcinosis, renal magnesium (Mg) wasting, hypercalciuria and kidney failure.	Rare genetic renal disease;Rare inborn errors of metabolism
Orphanet:31112	Dermatofibrosarcoma protuberans	COL1A1;PDGFB	2	Dermatofibrosarcoma protuberans (DFSP) is a rare infiltrating soft tissue sarcoma, generally of low grade malignancy, arising from the dermis of the skin and characteristically associated with a specific chromosomal translocation t(17;22).	Rare genetic tumor
Orphanet:30924	Primary hypomagnesemia with secondary hypocalcemia	TRPM6	1	Primary hypomagnesemia with secondary hypocalcemia (PHSH) is a form of familial primary hypomagnesemia (FPH, see this term), characterized by severe hypomagnesemia and secondary hypocalcemia associated with neurological symptoms, including generalized seizures, tetany and muscle spasms. PHSH may be fatal or may result in chronic irreversible neurological complications.	Rare genetic renal disease;Rare inborn errors of metabolism
Orphanet:30925	Hereditary central diabetes insipidus	AVP	1	Hereditary central diabetes insipidus is a rare genetic subtype of central diabetes insipidus (CDI, see this term) characterized by polyuria and polydipsia due to a deficiency in vasopressin (AVP) synthesis.	Rare genetic endocrine disease
Orphanet:476084	Autosomal recessive limb-girdle muscular dystrophy type 2X	BVES	1	A rare subtype of autosomal recessive limb-girdle muscular dystrophy characterized by atrioventricular block resulting in repeated syncope episodes, elevated creatine kinase serum levels and adult-onset of slowly progressive proximal limb skeletal muscle weakness and atrophy. Muscular dystrophic changes observed in muscle biopsy include diameter variability, increased central nuclei, and presence of necrotic and regenerating fibers.	Rare genetic neurological disorder;Rare genetic cardiac disease
Orphanet:476096	Erythrokeratodermia-cardiomyopathy syndrome	DSP	1	Erythrokeratodermia-cardiomyopathy syndrome is a rare, genetic erythrokeratoderma disorder characterized by generalized cutaneous erythema with fine white scales and pruritus refractory to treatment, progressive dilated cardiomyopathy, palmoplantar keratoderma, sparse or absent eyebrows and eyelashes, sparse scalp hair, nail dystrophy, and dental enamel anomalies. Variable features include failure to thrive, developmental delay, and development of corneal opacities. Histology shows psoriasiform acanthosis, hypogranulosis, and compact orthohyperkeratosis.	Rare genetic cardiac disease;Rare genetic skin disease
Orphanet:476102	Hereditary pediatric Behçet-like disease	TNFAIP3	1	NA	
Orphanet:476093	Autosomal dominant distal axonal motor neuropathy-myofibrillar myopathy syndrome	HSPB8	1	NA	Rare genetic neurological disorder
Orphanet:71278	Congenital brain dysgenesis due to glutamine synthetase deficiency	GLUL	1	NA	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:71271	Split hand-split foot-deafness syndrome	DLX5	1	Split hand - split foot - deafness is an extremely rare genetic syndrome reported in a few families to date and characterized clinically by split hand/split foot malformation (SHFM; see this term) and mild to moderate sensorineural hearing loss, sometimes associated with cleft palate and intellectual deficit.	Genetic otorhinolaryngologic disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:71275	Rh deficiency syndrome	RHCE;RHD;RHAG	3	NA	Rare genetic hematologic disease
Orphanet:71277	Classic glucose transporter type 1 deficiency syndrome	SLC2A1	1	Glucose transporter type 1 (GLUT1) deficiency syndrome is characterized by an encephalopathy marked by childhood epilepsy that is refractory to treatment, deceleration of cranial growth leading to microcephaly, psychomotor retardation, spasticity, ataxia, dysarthria and other paroxysmal neurological phenomena often occurring before meals. Symptoms appear between the age of 1 and 4 months, following a normal birth and gestation.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:71212	Hyperinsulinism due to short chain 3-hydroxylacyl-CoA dehydrogenase deficiency	HADH	1	Hyperinsulinism due to short chain 3 hydroxylacyl-CoA dehydrogenase (SCHAD) deficiency is a recently described mitochondrial fatty acid oxidation disorder characterized by hyperinsulinemic hypoglycemia with seizures, and in one case fulminant hepatic failure.	Rare genetic neurological disorder;Rare genetic endocrine disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:70592	Immunodeficiency due to interleukin-1 receptor-associated kinase-4 deficiency	IRAK4	1	Interleukin-1 receptor-associated kinase-4 (IRAK-4) deficiency is an immunodeficiency associated with increased susceptibility to invasive infections caused by pyogenic bacteria.	Rare genetic immune disease
Orphanet:70595	Sensory ataxic neuropathy-dysarthria-ophthalmoparesis syndrome	POLG;TWNK	2	Sensory ataxic neuropathy-dysarthria-ophthalmoparesis syndrome is characterised by adult-onset severe sensory ataxic neuropathy, dysarthria and chronic progressive external ophthalmoplegia.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:70594	Dopa-responsive dystonia due to sepiapterin reductase deficiency	SPR	1	Dopa-responsive dystonia (DRD) due to sepiapterin reductase deficiency (SRD) is a very rare neurometabolic disorder characterized by dystonia with diurnal fluctuations, axial hypotonia, oculogyric crises, and delays in motor and cognitive development.	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:70573	Small cell lung cancer	RB1;TP53;TP73	3	Small cell lung cancer (SCLC) is a highly aggressive malignant neoplasm, accounting for 10-15% of lung cancer cases, characterized by rapid growth, and early metastasis. SCLC usually manifests as a large hilar mass with bulky mediastinal lymphadenopathy presenting clinically with chest pain, persistent cough, dyspnea, wheezing, hoarseness, hemoptysis, loss of appetite, weight loss, and neurological and endocrine paraneoplastic syndromes. SCLC is primarily reported in elderly people with a history of long-term tobacco exposure.	
Orphanet:70587	Infant acute respiratory distress syndrome	SFTPB;SFTPC;ABCA3	3	Infant acute respiratory distress syndrome is a lung disorder that affects premature infants caused by developmental insufficiency of surfactant production and structural immaturity of the lungs. The symptoms usually appear shortly after birth and may include tachypnea, tachycardia, chest wall retractions (recession), expiratory grunting, nasal flaring and cyanosis during breathing efforts.	
Orphanet:70474	Leigh syndrome with cardiomyopathy	NDUFAF3;NDUFB8;SCO2;SURF1;NDUFS2	5	NA	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic eye disease;Rare genetic neurological disorder
Orphanet:70472	Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	LRPPRC	1	Saguenay-Lac-St. Jean (SLSJ) type congenital lactic acidosis, a French Canadian form of Leigh syndrome (see this term), is a mitochondrial disease characterized by chronic metabolic acidosis, hypotonia, facial dysmorphism and delayed development.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:70470	OBSOLETE: Hyperlipoproteinemia type 5	APOA5;CREB3L3;LPL	3	NA	NA
Orphanet:70567	Cholangiocarcinoma	PTPN3	1	Cholangiocarcinoma (CCA) is a biliary tract cancer (BTC, see this term) originating in the epithelium of the biliary tree, either intra or extra hepatic.	
Orphanet:69735	Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome	SOX18	1	Hypotrichosis - lymphedema - telangiectasia is an extremely rare syndromic lymphedema disorder characterized by early-onset hypotrichosis, childhood-onset lymphedema, and variable telangiectasia, particularly of the palms.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic renal disease
Orphanet:69737	Bosley-Salih-Alorainy syndrome	HOXA1	1	 gene (7p15.2) and is transmitted in an autosomal recessive manner. The syndrome overlaps clinically and genetically with Athabaskan brain dysfunction syndrome (ABDS,). However unlike ABDS, BSAS does not manifest central hypoventilation.	Genetic otorhinolaryngologic disease;Rare genetic developmental defect during embryogenesis;Rare genetic cardiac disease
Orphanet:69739	Athabaskan brainstem dysgenesis syndrome	HOXA1	1	A rare, genetic, neurological disorder characterized by horizontal gaze palsy, sensorineural deafness, central hypoventilation, developmental delay, and intellectual disability, described in persons of Athabascan American Indian heritage. Swallowing dysfunction, vocal cord paralysis, facial paresis, seizures, internal carotid artery, and cardiac outflow tract anomalies may be additionally observed. No dysmorphic facial features are associated.	Genetic otorhinolaryngologic disease
Orphanet:69663	Low phospholipid-associated cholelithiasis	ABCB4	1	Low phospholipid associated cholelithiasis is a rare genetic hepatic disease characterized by cholesterol gallstones and intrahepatic stones developing before the age of 40 years.	Rare genetic hepatic disease
Orphanet:69665	Intrahepatic cholestasis of pregnancy	NR1H4;ABCB11;ABCB4;ATP8B1	4	Intrahepatic cholestasis of pregnancy (ICP) is a cholestatic disorder characterized by (i) pruritus with onset in the second or third trimester of pregnancy, (ii) elevated serum aminotransferases and bile acid levels, and (iii) spontaneous relief of signs and symptoms within two to three weeks after delivery.	Rare genetic hepatic disease
Orphanet:69723	Tyrosinemia type 3	HPD	1	Tyrosinemia type 3 is an inborn error of tyrosine metabolism characterised by mild hypertyrosinemia and increased urinary excretion of 4-hydroxyphenylpyruvate, 4-hydroxyphenyllactate and 4-hydroxyphenylacetate.	Rare inborn errors of metabolism
Orphanet:69126	Pyogenic arthritis-pyoderma gangrenosum-acne syndrome	PSTPIP1	1	Pyogenic arthritis-pyoderma gangrenosum-acne syndrome is a rare pleiotropic autoinflammatory disorder of childhood, primarily affecting the joints and skin.	Rare genetic skin disease;Rare genetic immune disease
Orphanet:69087	Naegeli-Franceschetti-Jadassohn syndrome	KRT14	1	Naegeli-Franceschetti-Jadassohn (NFJ) syndrome is a rare ectodermal dysplasia that affects the skin, sweat glands, nails, and teeth.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:69088	Anhidrotic ectodermal dysplasia-immunodeficiency-osteopetrosis-lymphedema syndrome	IKBKG	1	This syndrome is characterized by severe immunodeficiency, osteopetrosis, lymphedema and anhidrotic ectodermal dysplasia.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic immune disease;Rare genetic bone disease
Orphanet:69085	Limb-mammary syndrome	TP63	1	Limb-mammary syndrome (LMS) is a rare disease belonging to the group of ectodermal dysplasias.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease;Rare genetic skin disease
Orphanet:69084	Pure hair and nail ectodermal dysplasia	KRT85;KRT74;HOXC13	3	Pure hair and nail ectodermal dysplasia is characterised by the association of onychodystrophy and severe hypotrichosis, which is mainly limited to the scalp but may also affect the eyelashes and eyebrows. Less than 20 cases have been reported so far. The mode of transmission is autosomal dominant.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:69076	Familial renal glucosuria	SLC5A2	1	A rare, genetic, glucose transport disorder characterized by the presence of persistent isolated glucosuria in the absence of both proximal tubular dysfunction and hyperglycemia. The disorder is benign in the majority of cases although it may occasionally manifest with polyuria, enuresis, a mild growth and pubertal maturation delay, hypercalciuria, aminoaciduria and, in severe cases, increased incidence of urinary infections and episodic dehydration and ketosis during pregnancy and starvation.	Rare inborn errors of metabolism;Rare genetic renal disease
Orphanet:67046	3-methylglutaconic aciduria type 1	AUH	1	3-methylglutaconic aciduria (3-MGA) type I is an inborn error of leucine metabolism with a variable clinical phenotype ranging from mildly delayed speech to psychomotor retardation, coma, failure to thrive, metabolic acidosis and dystonia.	Rare inborn errors of metabolism
Orphanet:67047	3-methylglutaconic aciduria type 3	C19ORF70;OPA3	2	3-methylglutaconic aciduria type III (MGA III) is an organic aciduria characterised by the association of optic atrophy and choreoathetosis with 3-methylglutaconic aciduria.	Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:67044	Thrombocytopenia with congenital dyserythropoietic anemia	GATA1	1	Thrombocytopenia with congenital dyserythropoietic anemia (CDA; see this term) is a rare hematological disorder, seen almost exclusively in males, characterized by moderate to severe thrombocytopenia with hemorrhages with or without the presence of mild to severe anemia.	Rare genetic hematologic disease
Orphanet:67045	X-linked intellectual disability with isolated growth hormone deficiency	SOX3	1	NA	Rare genetic neurological disorder
Orphanet:67042	Late-onset retinal degeneration	C1QTNF5	1	Late-onset retinal degeneration is an inherited retinal dystrophy characterized by delayed dark adaptation and nyctalopia and drusen deposits presenting in adulthood, followed by cone and rod degeneration that presents in the sixth decade of life, which leads to central vision loss. Anterior segment features such as peripupillary iris transillumination defects and abnormally long anterior zonular insertions are also observed. Choroidal neovascularization and glaucoma may occur in the late stages of the disease.	Rare genetic eye disease
Orphanet:67041	Hyaluronidase deficiency	HYAL1	1	NA	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:67038	B-cell chronic lymphocytic leukemia	P2RX7;IGHV3-21;ATM;CCND1;TP53;ARL11;IGHG1;POT1;RPS15;IKZF3	10	B-cell chronic lymphocytic leukemia (B-CLL) is a type of B-cell non-Hodgkin lymphoma (see this term), and the most common form of leukemia in Western countries, affecting elderly adults (mean age of 67 and 72 years) with a slight male predominance (1.7:1), and characterized by a highly variable clinical presentation that can include asymptomatic disease or non-specific B-symptoms such as unintentional weight loss, severe fatigue, fever (without evidence of infection), and night sweats as well as cervical lymphadenopathy, splenomegaly and frequent infections. Some patients can also develop autoimmune complications such as autoimmune hemolytic anemia or immune thrombocytopenia (see these terms). The clinical course is extremely heterogeneous with survival ranging from a few months to several decades.	
Orphanet:67036	Autosomal dominant optic atrophy and cataract	OPA3	1	 gene (19q13.32).	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:66637	Diaphanospondylodysostosis	BMPER	1	Diaphanospondylodysostosis is characterized by absent ossification of the vertebral bodies and sacrum associated with variable anomalies. It has been described in less than ten patients from different families. Manifestations include a short neck, a short wide thorax, a reduced number of ribs, a narrow pelvis, and inconstant anomalies such as myelomeningocele, cystic kidneys with nephrogenic rests, and cleft palate.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:66634	Dilated cardiomyopathy with ataxia	DNAJC19	1	Dilated cardiomyopathy with ataxia (DCMA) is characterized by severe early onset (before the age of three years) dilated cardiomyopathy (DCM) with conduction defects (long QT syndrome), non-progressive cerebellar ataxia, testicular dysgenesis, and 3-methylglutaconic aciduria.	Rare inborn errors of metabolism;Rare genetic cardiac disease
Orphanet:66631	CEDNIK syndrome	SNAP29	1	CEDNIK syndrome is a neurocutaneaous syndrome characterized by severe developmental abnormalities of the nervous system and aberrant differentiation of the epidermis.	Rare genetic neurological disorder;Rare genetic skin disease
Orphanet:66629	Goldberg-Shprintzen megacolon syndrome	KIF1BP	1	A rare multiple congenital anomalies/dysmorphic syndrome characterized by Hirschsprung disease, facial dysmorphism (sloping forehead, high arched eyebrows, long eyelashes, telecanthus/hypertelorism, ptosis, prominent ears, thick earlobes, prominent nasal bridge, thick philtrum, everted lower lip vermillion and pointed chin), global developmental delay, intellectual disability and variable cerebral abnormalities (focal or generalized polymicrogyria, or hypoplastic corpus callosum).	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic gastroenterological disease;Rare genetic eye disease
Orphanet:66628	Obesity due to congenital leptin deficiency	LEP	1	Congenital leptin deficiency is a form of monogenic obesity characterised by severe early-onset obesity and marked hyperphagia.	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility;Rare genetic developmental defect during embryogenesis
Orphanet:65283	Timothy syndrome	CACNA1C	1	A multi-system disorder characterized by cardiac, hand, facial and neurodevelopmental features that include QT prolongation, webbed fingers and toes, flattened nasal bridge, low-set ears, small upper jaw, thin upper lip, and characteristic features of autism or autistic spectrum disorders.	Rare genetic cardiac disease
Orphanet:65282	Carvajal syndrome	DSP	1	A syndrome that is characterized by woolly hair, palmoplantar keratoderma and dilated cardiomyopathy principally affecting the left ventricle.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic cardiac disease
Orphanet:65285	Lhermitte-Duclos disease	PTEN	1	A very rare disorder characterized by abnormal development and enlargement of the cerebellum, and an increased intracranial pressure.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:65284	Biotin-thiamine-responsive basal ganglia disease	SLC19A3	1	NA	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:65287	Beta-ureidopropionase deficiency	UPB1	1	Beta-ureidopropionase deficiency is a very rare pyrimidine metabolism disorder described in fewer than 10 patients to date with an extremely wide clinical picture ranging from asymptomatic cases to neurological (epilepsy, autism) and developmental disorders (urogenital, colorectal).	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:65288	Permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome	PTF1A	1	Permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome is characterized by neonatal diabetes mellitus associated with cerebellar and/or pancreatic agenesis.	Rare genetic endocrine disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:65684	Monomelic amyotrophy	CPLANE1;CEP126	2	Monomelic amyotrophy (MA) is a rare benign lower motor neuron disorder characterized by muscular weakness and wasting in the distal upper extremities during adolescence followed by a spontaneous halt in progression and a stabilization of symptoms.	
Orphanet:65748	Multiple self-healing squamous epithelioma	TGFBR1	1	Multiple self-healing squamous epithelioma (also known as Ferguson-Smith disease (FSD)) is a rare inherited skin cancer syndrome characterized by the development of multiple locally invasive skin tumors resembling keratoacanthomas of the face and limbs which usually heal spontaneously after several months leaving pitted scars.	Rare genetic tumor
Orphanet:65743	Autosomal dominant multiple pterygium syndrome	MYH3	1	A rare distal arthrogryposis syndrome characterized by multiple pterygia (typically involving the neck, axilla and popliteal areas), joint contractures, ptosis, camptodactyly of the hands with hypoplastic flexion creases, vertebral fusions, severe scoliosis and short stature.	Rare genetic developmental defect during embryogenesis
Orphanet:65759	Carpenter syndrome	MEGF8;RAB23	2	Carpenter syndrome is a subtype of a family of genetic disorders known as acrocephalopolysyndactyly (ACPS) disorders.	Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease;Rare genetic bone disease
Orphanet:64748	Dejerine-Sottas syndrome	PMP22;PRX;EGR2;MPZ	4	 (19q13.2) have been implicated.	Rare genetic neurological disorder
Orphanet:64751	Hereditary motor and sensory neuropathy type 5	MFN2	1	Hereditary motor and sensory neuropathy type 5 is a rare axonal hereditary motor and sensory neuropathy characterized by slowly progressive distal muscle weakness and atrophy with or without sensory loss resulting in difficulty in walking, foot drop and pes cavus, that may be associated with pyramidal signs (extensor plantar responses, mild increase in tone, brisk tendon reflexes), muscle cramps, pain and spasticity.	Rare genetic neurological disorder
Orphanet:64752	Hereditary sensory and autonomic neuropathy type 5	NTRK1;NGF	2	A disorder that is characterized by loss of pain perception and impaired temperature sensitivity, in the absence of any other major neurological anomalies.	Rare genetic neurological disorder
Orphanet:64753	Spinocerebellar ataxia with axonal neuropathy type 2	SETX;PIK3R5	2	A rare autosomal recessive cerebellar ataxia (ARCA), characterized by progressive cerebellar ataxia associated with frequent oculomotor apraxia, severe neuropathy and an elevated serum alpha-fetoprotein (AFP) level.	Rare genetic eye disease;Rare genetic neurological disorder
Orphanet:64754	Nevus comedonicus syndrome	NEK9	1	A rare, syndromic nevus characterized by the association of typically unilateral, closely arranged, linear, slightly elevated, multiple, nevus comedonicus lesions located usually on the face, neck, trunk or limbs (with or without a central, dark, firm, hyperkeratotic plug and secondary acneiform lesions) with extracutaneous ocular, skeletal, and/or central nervous system abnormalities, such as ipsilateral cataract, corneal erosion, poly-/syndactyly, absent fifth finger, scoliosis, vertebral defects, corpus callosum agenesis, seizures, interhemispheric cyst, intellectual deficiency, and/or developmental delay.	Rare genetic tumor
Orphanet:64755	Becker nevus syndrome	ACTB	1	A rare, syndromic, benign, epidemal nevus syndrome characterized by the association of a Becker nevus (i.e. circumscribed, unilateral, irregularly shaped, hyperpigmented macules, with or without hypertrichosis and/or acneiform lesions, occuring predominantly on the anterior upper trunk or scapular region) with ipsilateral breast hypoplasia or other, typically hypoplastic, skeletal, cutaneous, and/or muscular defects, such as pectoralis major hypoplasia, supernumerary nipples, vertebral defects, scoliosis, limb asymmetry, odontomaxillary hypoplasia and lipoatrophy.	Rare genetic tumor;Rare genetic developmental defect during embryogenesis
Orphanet:64280	Childhood absence epilepsy	GABRA1;GABRG2;SLC2A1;GABRB3;JRK;CACNA1H	6	Childhood absence epilepsy (CAE) is a familial generalized pediatric epilepsy, characterized by very frequent (multiple per day) absence seizures, usually occurring in children between the ages of 4 and 10 years, with, in most cases, a good prognosis.	Rare genetic neurological disorder
Orphanet:64739	Ovarian hyperstimulation syndrome	FSHR	1	NA	
Orphanet:63260	Craniorachischisis	DACT1	1	Craniorachischisis is the most severe form of neural tube defect in which both the brain and spinal cord remain open to varying degrees. It is a very rare congenital malformation of the central nervous system.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:63440	Isolated oxycephaly	ZIC1	1	Isolated oxycephaly is a late-appearing form of nonsyndromic craniosynostosis characterized by premature fusion of both the coronal and sagittal sutures, and, in some cases, of the lambdoid sutures. Compensatory growth in the region of the anterior fontanel results in a pointed or cone-shaped skull.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease
Orphanet:63442	Angel-shaped phalango-epiphyseal dysplasia	GDF5	1	A form of acromelic dysplasia characterized by the distinctive radiological sign of angel-shaped middle phalanges, a typical metacarpophalangeal pattern profile (mainly affecting first metacarpals and middle phalanges of second, third and fifth digits, which all appear short), epiphyseal changes in the hips and, in some, abnormal dentition and delayed bone age.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:63273	Distal myopathy with posterior leg and anterior hand involvement	FLNC	1	Distal myopathy with posterior leg and anterior hand involvement, also named distal ABD-filaminopathy, is a neuromuscular disease characterized by a progressive symmetric muscle weakness of anterior upper and posterior lower limbs.	Rare genetic neurological disorder
Orphanet:63446	Acrocapitofemoral dysplasia	IHH	1	A rare skeletal dysplasi, characterized clinically by short stature of variable degrees with short limbs, brachydactyly and narrow thorax.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:60040	Megalencephaly-capillary malformation-polymicrogyria syndrome	PIK3CA	1	Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP) is a polymalfomative syndrome characterized by cutaneous capillary malformations, megalencephaly, cortical brain malformations (most distinctively polymicrogyria), abnormalities of somatic growth with body and brain asymmetry, developmental delay, and characteristic facial dysmorphism.	Rare genetic skin disease;Inherited cancer-predisposing syndrome;Rare genetic developmental defect during embryogenesis
Orphanet:60033	Idiopathic bronchiectasis	CFTR;SCNN1A;SCNN1B;SCNN1G	4	#160;(IB) is a progressive lung disease characterized by chronic dilation of the bronchi and destruction of the bronchial walls in the absence of any underlying cause (such as post infectious disease, aspiration, immunodeficiency, congenital abnormalities and ciliary anomalies).	
Orphanet:59303	Neonatal ichthyosis-sclerosing cholangitis syndrome	CLDN1	1	Neonatal ichthyosis-sclerosing cholangitis (NISCH syndrome) is a very rare complex ichthyosis syndrome characterized by scalp hypotrichosis, scarring alopecia, ichthyosis and sclerosing cholangitis.	Rare genetic hepatic disease;Rare genetic skin disease
Orphanet:59306	McLeod neuroacanthocytosis syndrome	XK	1	McLeod neuroacanthocytosis syndrome (MLS) is a form of neuroacanthocytosis (see this term) and is characterized clinically by a Huntington's disease-like phenotype with an involuntary hyperkinetic movement disorder, psychiatric manifestations and cognitive alterations, and biochemically by absence of the Kx antigen and by weak expression of the Kell antigens.	Rare genetic neurological disorder;Rare genetic cardiac disease;Rare genetic hematologic disease
Orphanet:60015	Enlarged parietal foramina	ALX4;MSX2	2	Enlarged parietal foramina (EPF) is a developmental defect, characterized by variable intramembranous ossification defects of the parietal bones, which is either asymptomatic, symptomatic (headaches, nausea, vomiting, intellectual disability) or associated with other pathologies.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:60025	Pulmonary alveolar microlithiasis	SLC34A2	1	NA	
Orphanet:60030	Loeys-Dietz syndrome	TGFBR1;TGFBR2	2	Loeys-Dietz syndrome is a rare genetic connective tissue disorder characterized by a broad spectrum of craniofacial, vascular and skeletal manifestations with four genetic subtypes described forming a clinical continuum.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic systemic or rheumatologic disease;Rare genetic vascular disease
Orphanet:59181	Sorsby pseudoinflammatory fundus dystrophy	TIMP3	1	Sorsby's fundus dystrophy is a rare progressive autosomal dominant macular dystrophy, presenting between the third and sixth decades of life, characterized by retinal atrophy and retinal detachment and leading to loss of central vision, then peripheral vision, and eventually blindness.	Rare genetic eye disease
Orphanet:59135	Laing early-onset distal myopathy	MYH7	1	Laing distal myopathy, also called myopathy distal, type 1 (MPD1), is characterized by early-onset selective weakness of the great toe and ankle dorsiflexors, and a very slowly progressive course.	Rare genetic neurological disorder
Orphanet:58017	Classic hairy cell leukemia	BRAF	1	Hairy cell leukemia (HCL) is a rare type of leukemia in which abnormal B-lymphocytes are present in the bone marrow, spleen and peripheral blood. It is a slowly progressive chronic lymphocytic leukemia (CLL). The name comes from the abnormally shaped lymphocytes with hair-like projections.	
Orphanet:57782	Mazabraud syndrome	GNAS	1	Mazabraud syndrome is a rare primary bone dysplasia (see this term) characterized by the association of fibrous dysplasia with intramuscular myxomas. Fibrous dysplasia (usually polyostotic, sometimes monostotic) occurs during the growth period and can be asymptomatic or can present with pain, skeletal deformities or fractures while intramuscular myxoma, associated with polyostotic fibrous dysplasia (see this term) is usually multifocal, typically occuring in the vicinity of skeletal lesions, and presents in adulthood as a painless soft-tissue mass (most commonly in the thigh). Although it is a benign condition, local recurrences of myxomas after incomplete excision and malignant transformation of a fibrous dysplastic lesion into osteogenic sarcoma have been reported.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:55595	Autosomal dominant limb-girdle muscular dystrophy type 1F	TNPO3	1	A rare subtype of autosomal dominant limb-girdle muscular dystrophy ,with a variable age of onset, characterized by progressive, proximal weakness and wasting of the shoulder and pelvic musculature (with the pelvic girdle, and especially the ileopsoas muscle, being more affected) and frequent association of calf hypertrophy, dysphagia, arachnodactyly with or without finger contractures and/or distal and axial muscle involvement. Additional features include an abnormal gait, exercise intolerance, myalgia, fatigue and respiratory insufficiency. Cardiac conduction defects are typically not observed.	Rare genetic neurological disorder
Orphanet:55596	Autosomal dominant limb-girdle muscular dystrophy type 1G	HNRNPDL	1	A rare, mild subtype of autosomal dominant limb-girdle muscular dystrophy characterized by a typically adult onset of mild, progressive, proximal weakness of pelvic and shoulder girdle muscles and progressive, permanent finger and toes flexion limitation without flexion contractures. Normal to highly elevated creatine kinase serum levels are observed.	Rare genetic neurological disorder
Orphanet:54595	Craniopharyngioma	BRAF;CTNNB1	2	Craniopharyngiomas are benign slow growing tumours that are located within the sellar and parasellar regions of the central nervous system.	Rare genetic endocrine disease
Orphanet:56304	Atelosteogenesis type II	SLC26A2	1	A rare, lethal perinatal bone dysplasia characterized by limb shortening, normal sized skull with cleft palate, hitchhiker thumbs, distinctive facial dysmorphism and radiographic skeletal features, caused by mutations in the diastrophic dysplasia sulfate transporter gene.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:56305	Atelosteogenesis type III	FLNB	1	A rare skeletal dysplasia characterized by short limbs dysmorphic facies and diagnostic radiographic findings.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:55880	Chondrosarcoma	EXT1	1	Chondrosarcoma is a malignant bone tumor arising from cartilaginous tissue, most frequently occuring at the ends of the femur and tibia, the proximal end of the humerus and the pelvis; and presenting with a palpable mass and progressive pain. Chondrosarcoma is usually slow growing at low histological grades and can be well managed by intralesional curettage or en-block wide resection.	
Orphanet:55654	Hypotrichosis simplex	LIPH;APCDD1;RPL21;SNRPE;LPAR6;DSG4	6	Hypotrichosis simplex (HS) or hereditary hypotrichosis simplex (HHS) is characterized by reduced pilosity over the scalp and body (with sparse, thin, and short hair) in the absence of other anomalies.	Rare genetic skin disease
Orphanet:79233	Hypoxanthine guanine phosphoribosyltransferase partial deficiency	HPRT1	1	Kelley-Seegmiller syndrome (KSS) is the mildest form of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency (see this term), a hereditary disorder of purine metabolism, and is associated with uric acid overproduction (UAO) leading to urolithiasis, and early-onset gout.	Rare inborn errors of metabolism;Rare genetic neurological disorder;Rare genetic hematologic disease;Rare genetic renal disease
Orphanet:79230	Hemochromatosis type 2	HAMP;HJV	2	Hemochromatosis type 2 (juvenile) is the early-onset and most severe form of rare hereditary hemochromatosis (HH; see this term), a group of diseases characterized by excessive tissue iron deposition of genetic origin.	Rare genetic hepatic disease;Rare inborn errors of metabolism
Orphanet:79237	Galactokinase deficiency	GALK1	1	A rare mild form of galactosemia characterized by early onset of cataract and an absence of the usual signs of classic galactosemia, i.e. feeding difficulties, poor weight gain and growth, lethargy, and jaundice.	Rare genetic eye disease;Rare inborn errors of metabolism;Rare genetic renal disease
Orphanet:79234	Crigler-Najjar syndrome type 1	UGT1A1	1	A hereditary disorder of hepatic bilirubin conjugation, characterized by severe neonatal unconjugated hyperbilirubinemia due to a complete absence of hepatic bilirubin glucuronosyltransferase (BGT).	Rare genetic hepatic disease;Rare inborn errors of metabolism
Orphanet:79235	Crigler-Najjar syndrome type 2	UGT1A1	1	A hereditary disorder of bilirubin metabolism characterized by unconjugated hyperbilirubinemia due to reduced and inducible activity of hepatic bilirubin glucuronosyltransferase (GT). Crigler-Najjar syndrome type 2 (CNS2) is a milder form of Crigler-Najjar syndrome (CNS) than Crigler-Najjar syndrome type 1 (CNS1).	Rare genetic hepatic disease;Rare inborn errors of metabolism
Orphanet:79157	2-methylbutyryl-CoA dehydrogenase deficiency	ACADSB	1	 gene (located on chromosome 10q25-26) have been reported in affected patients. Treatment includes carnitine supplementation and a low-protein diet.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:79155	Hydroxykynureninuria	KYNU	1	A rare, genetic disorder of tryptophan metabolism characterized by massive urinary excretion of xanthurenic acid (XA), 3-hydroxykynurenine and kynurenine and increased XA concentration in plasma. The clinical phenotype is highly variable, ranging from asymptomatic or mild cases presentating with jaundice and vomiting, with subsequent normal development and growth, to more severe cases with manifestions which include intellectual disability, cerebellar ataxia, pellagra, progressive encephalopathy with muscular hypotonia, global developmental delay, stereotyped gestures and/or congenital deafness.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:79154	2-aminoadipic 2-oxoadipic aciduria	DHTKD1	1	2-aminoadipic 2-oxoadipic aciduria is a rare disorder of lysine and hydroxylysine metabolism characterized by variable clinical presentation including hypotonia, developmental delay, mild to severe intellectual disability, ataxia, epilepsy and behavioral disorders, most commonly attention deficit hyperactivity disorder. Frequently, individuals are completely without clinical phenotype.	Rare inborn errors of metabolism
Orphanet:79152	Disseminated superficial actinic porokeratosis	MVK;SLC17A9;MVD;FDPS	4	Disseminated superficial actinic porokeratosis (DSAP) is the most common form of porokeratosis characterized by the presence of several small annular plaques with a distinctive keratotic rim found most commonly on sun-exposed areas of the skin, particularly the extremities.	Rare genetic skin disease
Orphanet:79151	Acrokeratosis verruciformis of Hopf	ATP2A2	1	"A rare, genetic, acrokeratoderma disease characterized by multiple, symmetrical, asymptomatic, skin-colored (rarely, brownish), flat-topped, wart-like papules located on the dorsal aspects of the hands and feet (occasionally found on other parts of the body, such as knees, elbows and forearms), typically associated with palmoplantar punctate keratosis and variable nail involvement (including leukonychia, thickening, ridging, longitudinal striations and splitting). Histology reveals undulating hyperkeratosis, papillomatosis, hypergranulosis, and acanthosis, creating a characteristic ""church spire"" appearance, with no acantholysis nor dyskeratosis associated."	Rare genetic skin disease
Orphanet:79146	Familial progressive hyperpigmentation	KITLG	1	Familial progressive hyperpigmentation is a rare, genetic, skin pigmentation anomaly disorder characterized by irregular patches of hyperpigmented skin which present at birth or in early infancy and increase in size, number and confluence with age. Affected areas of the body include the face, neck, trunk and limbs, as well as the palms, soles, oral mucosa and conjuctiva. No hypogmentation macules are observed and no systemic diseases are associated.	Rare genetic skin disease
Orphanet:79145	Dowling-Degos disease	PSENEN;KRT5;POFUT1;POGLUT1	4	A rare, genetic, hyperpigmentation of the skin disease characterized by adulthood-onset of reticular, reddish-brown to dark-brown, macular and/or comedone-like, hyperkeratotic papules with hypopigmented macules, predominantly affecting flexural areas and, on occasion, progressing to involve trunk and acral regions. Histologically, epidermal acanthosis, thin, branch-like, rete ridges, and a tendency for acantholysis and pigmentary incontinence is observed.	Rare genetic skin disease;Rare inborn errors of metabolism
Orphanet:79159	Isobutyryl-CoA dehydrogenase deficiency	ACAD8	1	 gene (11q25).	Rare inborn errors of metabolism;Rare genetic cardiac disease
Orphanet:79107	Developmental malformations-deafness-dystonia syndrome	ACTB	1	Developmental malformations-deafness-dystonia syndrome is characterised by the association of midline malformations, sensory hearing loss, and a delayed-onset generalised dystonia syndrome.	Genetic otorhinolaryngologic disease;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic neurological disorder
Orphanet:79106	Eiken syndrome	PTH1R	1	A rare, genetic, primary bone dysplasia syndrome characterized by multiple epiphyseal dysplasia, severely delayed ossification (mainly of the epiphyses, pubic symphysis, hands and feet), abnormal modeling of the bones in hands and feet, abnormal pelvis cartilage persistence, and mild growth retardation. Calcium, phosphate and vitamin D serum levels are typically within normal range, while parathyroid hormone serum levels are normal to slighly elevated. Oligodontia has been rarely associated.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:79118	Neonatal diabetes-congenital hypothyroidism-congenital glaucoma-hepatic fibrosis-polycystic kidneys syndrome	GLIS3	1	 encoding for the transcription factor GLI similar 3 seem to be responsible of the syndrome.	Rare genetic renal disease
Orphanet:79113	Mandibulofacial dysostosis-microcephaly syndrome	EFTUD2	1	Mandibulofacial dysostosis-microcephaly syndrome is a rare genetic multiple malformation disorder characterized by malar and mandibular hypoplasia, microcephaly, ear malformations with associated conductive hearing loss, distinctive facial dysmorphism, developmental delay, and intellectual disability.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:79102	Thyrotoxic periodic paralysis	CACNA1S;GABRA3;KCNJ18	3	Thyrotoxic periodic paralysis (TPP) is a rare neurological disease characterized by recurrent episodes of paralysis and hypokalemia during a thyrotoxic state.	Rare genetic neurological disorder
Orphanet:79105	Myxofibrosarcoma	FUS;CREB3L2;CREB3L1	3	NA	
Orphanet:79101	Hyperprolinemia type 2	ALDH4A1	1	Hyperprolinemia type 2 is an autosomal recessive proline metabolism disorder due to pyroline-5-carboxylate dehydrogenase deficiency. The condition is often benign but clinical signs may include seizures, intellectual deficit and mild developmental delay.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:79100	Atrophoderma vermiculata	LRP1	1	NA	Rare genetic skin disease
Orphanet:79095	Congenital bile acid synthesis defect type 4	AMACR	1	Congenital bile acid synthesis defect type 4 (BAS defect type 4) is an anomaly of bile acid synthesis (see this term) characterized by mild cholestatic liver disease, fat malabsorption and/or neurological disease.	Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic hepatic disease
Orphanet:79094	Grange syndrome	YY1AP1	1	Grange syndrome is characterised by stenosis or occlusion of multiple arteries (including the renal, cerebral and abdominal vessels), hypertension, brachysyndactyly, syndactyly, increased bone fragility, and learning difficulties or borderline intellectual deficit. Congenital heart defects were also reported in some cases.	Rare genetic developmental defect during embryogenesis
Orphanet:79096	Pyridoxal phosphate-responsive seizures	PNPO	1	Pyridoxal phosphate-responsive seizures is a very rare neonatal epileptic encephalopathy disorder characterized clinically by onset of severe seizures within hours of birth that are not responsive to anticonvulsants, but are responsive to treatment with pyridoxal phosphate.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:79134	DEND syndrome	ABCC8;KCNJ11	2	DEND syndrome is a very rare, generally severe form of neonatal diabetes mellitus (NDM, see this term) characterized by a triad of developmental delay, epilepsy, and neonatal diabetes.	Rare genetic neurological disorder;Rare genetic endocrine disease
Orphanet:79137	Generalized epilepsy-paroxysmal dyskinesia syndrome	KCNMA1	1	 gene (chromosome 10q22), encoding the alpha subunit of the BK channel. Transmission is autosomal dominant.	Rare genetic neurological disorder
Orphanet:79124	Hepatic veno-occlusive disease-immunodeficiency syndrome	SP110	1	Hepatic veno-occlusive disease-immunodeficiency syndrome is characterized by the association of severe hypogammaglobulinemia, combined T and B cell immunodeficiency, absent lymph node germinal centers, absent tissue plasma cells and hepatic veno-occlusive disease.	Rare genetic immune disease
Orphanet:77293	Niemann-Pick disease type B	SMPD1	1	Niemann-Pick disease type B is a mild subtype of Niemann-Pick disease, an autosomal recessive lysosomal disease, and is characterized clinically by onset in childhood with hepatosplenomegaly, growth retardation, and lung disorders such as infections and dyspnea	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:77295	Odontoleukodystrophy	POLR3A	1	Leukodystrophy with oligodontia is characterised by progressive ataxia beginning during infancy, a pyramidal syndrome and dental agenesis. The syndrome has been described in four children born to consanguineous parents. The mode of transmission is autosomal recessive.	Rare genetic neurological disorder
Orphanet:77261	Gaucher disease type 3	GBA	1	Gaucher disease type 3 is the subacute neurological form of Gaucher disease (GD; see this term) characterized by progressive encephalopathy and associated with the systemic manifestations (organomegaly, bone involvement, cytopenia) of GD type 1 (see this term).	Rare genetic eye disease;Rare genetic neurological disorder;Rare genetic cardiac disease;Rare inborn errors of metabolism;Rare genetic bone disease
Orphanet:77292	Niemann-Pick disease type A	SMPD1	1	Niemann-Pick disease type A is a very severe subtype of Niemann-Pick disease, an autosomal recessive lysosomal disease, and is characterized clinically by onset in infancy or early childhood with failure to thrive, hepatosplenomegaly, and rapidly progressive neurodegenerative disorders.	Rare genetic neurological disorder;Rare genetic eye disease;Rare inborn errors of metabolism
Orphanet:77298	Anophthalmia/microphthalmia-esophageal atresia syndrome	SOX2	1	A syndrome that belongs to the group of syndromic microphthalmias and is characterized by the association of uni- or bilateral anophthalmia or microphthalmia, and esophageal atresia with or without trachoesophageal fistula.	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic endocrine disease
Orphanet:77297	Majeed syndrome	LPIN2	1	Majeed syndrome is a rare genetic multisystemic disorder characterized by chronic recurrent multifocal osteomyelitis, congenital dyserythropoietic anemia, which may be accompanied by neutrophilic dermatosis.	Rare genetic immune disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic hematologic disease
Orphanet:77301	Monosomy 9q22.3	PTCH1	1	Interstitial 9q22.3 microdeletion is associated with a phenotype including macrocephaly, overgrowth and trigonocephaly. Psychomotor delay, hyperactivity and distinctive facial features were also observed. It has been described in two unrelated children.	Rare genetic eye disease;Rare chromosomal anomaly
Orphanet:79083	PPARG-related familial partial lipodystrophy	PPARG	1	NA	Rare genetic skin disease;Rare genetic endocrine disease
Orphanet:79076	Juvenile polyposis of infancy	PTEN;BMPR1A	2	Juvenile polyposis of infancy (JPI) is the most severe form of juvenile gastrointestinal polyposis (see this term) and is characterized by pancolonic hamartomatous polyposis from stomach to rectum, diagnosed in the first two years of life.	Rare genetic gastroenterological disease;Inherited cancer-predisposing syndrome;Rare chromosomal anomaly
Orphanet:79087	Acquired partial lipodystrophy	LMNB2	1	A rare acquired lipodystrophy characterized by bilateral, symmetrical lipoatrophy of the upper body (face, neck, arms, thorax and sometimes upper abdomen) with sparing of the lower extremities and cephalothoracic progression. The disease may be associated with low serum levels of C3 and presence of C3-nephritic factor.	Rare genetic skin disease
Orphanet:79085	AKT2-related familial partial lipodystrophy	AKT2	1	NA	Rare genetic skin disease;Rare genetic endocrine disease
Orphanet:79084	Familial partial lipodystrophy, Köbberling type	LMNA	1	Familial partial lipodystrophy, Köbberling type, is a very rare form of familial partial lipodystrophy (FPLD; see this term) of unknown etiology characterized by lipoatrophy that is confined to the limbs and a normal or increased fat distribution of the face, neck, and trunk. Arterial hypertension and diabetes have also been associated. Inheritance is thought to be autosomal dominant.	Rare genetic skin disease;Rare genetic endocrine disease;Laminopathy
Orphanet:79091	Hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome	MYH2	1	Hereditary inclusion body myopathy type 3 is characterised by congenital joint contractures (normalizing during early childhood), external ophthalmoplegia, and proximal muscle weakness. In adult cases, the muscular weakness is progressive.	Rare genetic neurological disorder
Orphanet:75327	North Carolina macular dystrophy	DHS6S1	1	North Carolina macular dystrophy (NCMD) is a non-progressive autosomal dominant macular disorder of congenital or infantile onset characterized by loss of central vision, the accumulation of drusen in the macula and atrophy of photoreceptor cells with a variable phenotype at macular examination.	Rare genetic eye disease
Orphanet:75374	Bradyopsia	RGS9BP;RGS9	2	Bradyopsia is characterised by prolonged electroretinal response suppression leading to difficulties adjusting to changes in luminance, normal to subnormal acuity and photophobia.	Rare genetic eye disease
Orphanet:75376	Familial drusen	CFI;CFH;EFEMP1	3	NA	Rare genetic eye disease
Orphanet:75377	Central areolar choroidal dystrophy	GUCA1A;PRPH2;GUCY2D	3	Central areolar choroidal dystrophy (CACD) is a hereditary macular disorder, usually presenting between the ages of 30-60, characterized by a large area of atrophy in the centre of the macula and the loss or absence of photoreceptors, retinal pigment epithelium and choriocapillaris in this area, resulting in a progressive decrease in visual acuity.	Rare genetic eye disease
Orphanet:75382	Oguchi disease	SAG;GRK1	2	Oguchi disease is an autosomal recessive retinal disorder characterized by congenital stationary night blindness (see this term) and the Mizuo-Nakamura phenomenon.	Rare genetic eye disease
Orphanet:75391	Primary immunodeficiency with natural-killer cell deficiency and adrenal insufficiency	MCM4	1	The primary immunodeficiency with natural-killer cell deficiency and adrenal insufficiency is characterised by a specific natural-killer (NK) cell deficiency and susceptibility to viral diseases. It has been described in four children from a large inbred kindred. Three out of the four children reported developed a viral illness. The mode of transmission is most likely autosomal recessive. The causative gene has been localised to within a 12-Mb region on chromosome 8p11.23-q11.21.	Rare genetic immune disease
Orphanet:75392	Periodontal Ehlers-Danlos syndrome	C1S;C1R	2	Ehlers-Danlos syndromes (EDS) form a heterogeneous group of hereditary connective tissue diseases characterized by joint hyperlaxity, cutaneous hyperelasticity and tissue fragility.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic systemic or rheumatologic disease
Orphanet:75496	B4GALT7-related spondylodysplastic Ehlers-Danlos syndrome	B4GALT7;B3GALT6	2	Ehlers-Danlos syndrome, progeroid type (EDS-PF) is a form of Ehlers-Danlos syndrome characterized by a premature aging with sparse hair, macrocephaly, loose elastic skin, failure to thrive, joint laxity, psychomotor retardation, hypotonia, and defective wound healing with atrophic scars.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic skin disease;Rare genetic systemic or rheumatologic disease;Rare inborn errors of metabolism
Orphanet:75563	X-linked sideroblastic anemia	ALAS2	1	X-linked sideroblastic anemia is a constitutional microcytic, hypochromic anemia of varying severity that is clinically characterized by manifestations of anemia and iron overload and that may respond to treatment with pyridoxine and folic acid.	Rare inborn errors of metabolism;Rare genetic hematologic disease
Orphanet:75564	Acquired idiopathic sideroblastic anemia	TET2;SF3B1	2	A rare myelodysplastic syndrome (MDS) characterized by ineffective hemopoiesis affecting one or more blood cell lineages (myeloid, erythroid or megakaryocytic) leading to peripheral blood cytopenias and an increased risk of developing leukaemia.	
Orphanet:75857	6q terminal deletion syndrome	ERMARD	1	6q terminal deletion syndrome is marked by a characteristic facial dysmorphism, short neck and psychomotor retardation, generally associated with a range of non-specific malformations.	Rare genetic developmental defect during embryogenesis;Rare chromosomal anomaly
Orphanet:75840	Congenital muscular dystrophy, Ullrich type	COL6A1;COL6A2;COL6A3;COL12A1	4	Ullrich congenital muscular dystrophy (UCMD) is characterized by early-onset, generalized and slowly progressive muscle weakness, multiple proximal joint contractures, marked hypermobility of the distal joints and normal intelligence.	Rare genetic neurological disorder
Orphanet:75858	MORM syndrome	INPP5E	1	MORM syndrome is characterised by the association of intellectual deficit, truncal obesity, retinal dystrophy and micropenis. It has been described in 14 individuals from a consanguineous family. It is transmitted in an autosomal recessive manner. The causative locus has been mapped to chromosome region 9q34.	Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease;Rare genetic eye disease;Ciliopathy
Orphanet:77258	Trichorhinophalangeal syndrome type 1 and 3	TRPS1	1	Trichorhinophalangeal syndromes (TRPS) type 1 and 3 are malformation syndromes characterized by short stature, sparse hair, a bulbous nasal tip and cone-shaped epiphyses, as well as severe generalized shortening of all phalanges, metacarpals and metatarsal bones.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic skin disease
Orphanet:77260	Gaucher disease type 2	GBA	1	Gaucher disease type 2 is the acute neurological form of Gaucher disease (GD; see this term). It is characterized by early-onset and severe neurological involvement of the brainstem, associated with an organomegaly and generally leading to death before the age of 2.	Rare genetic eye disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:77259	Gaucher disease type 1	GBA;SCARB2	2	Gaucher disease type 1 is the chronic non-neurological form of Gaucher disease (GD; see this term) characterized by organomegaly, bone involvement and cytopenia.	Rare genetic eye disease;Rare genetic cardiac disease;Rare inborn errors of metabolism;Rare genetic bone disease;Rare genetic neurological disorder
Orphanet:73272	Growth delay due to insulin-like growth factor type 1 deficiency	IGF1	1	Growth delay due to insulin-like growth factor I deficiency is characterised by the association of intrauterine and postnatal growth retardation with sensorineural deafness and intellectual deficit.	Rare genetic endocrine disease
Orphanet:73273	Growth delay due to insulin-like growth factor I resistance	IGF1R	1	Growth delay due to IGF-I resistance is characterised by variable intrauterine and postnatal growth retardation and elevated serum IGF-I levels. Addition features include variable degrees of intellectual deficit, microcephaly and dysmorphism (broad nasal bridge and tip, smooth philtrum, thin upper and everted lower lips, short fingers, clinodactyly, wide-set nipples and pectus excavatum).	Rare genetic endocrine disease
Orphanet:75326	Retinal arterial tortuosity	COL4A1	1	NA	Rare genetic neurological disorder
Orphanet:75249	Familial isolated restrictive cardiomyopathy	FLNC;KIF20A;TNNI3;TNNT2;MYPN	5	NA	Rare genetic cardiac disease
Orphanet:75234	Cholesteryl ester storage disease	LIPA	1	Cholesteryl ester storage disease (CESD) is a very rare, late-onset, genetic endocrine disease characterized by deficient or inactive lysosomal acid lipase (LAL) causing lipid build-up, which leads to atherosclerosis, hepatomegaly, splenomegaly, progressive liver disease, and malabsorption.	Rare genetic hepatic disease;Rare inborn errors of metabolism;Rare genetic endocrine disease
Orphanet:75233	Wolman disease	LIPA	1	Wolman disease represents the most severe manifestation of lysosomal acid lipase deficiency. Milder phenotypes as a whole are referred to as cholesterol ester storage disease (see this term). The acid lipase enzyme plays an essential role in lysosomal hydrolysis of both esterified cholesterol and triglycerides of lipoproteic origin. In Wolman disease, the rarest form of acid lipase deficiency, these lipids accumulate in most tissues.	Rare genetic hepatic disease;Rare inborn errors of metabolism;Rare genetic endocrine disease
Orphanet:71290	Familial platelet disorder with associated myeloid malignancy	ETV6;ANKRD26;RUNX1	3	A rare, genetic, constitutional thrombocytopenia disease characterized by mild to moderate thrombocytopenia, abnormal platelet function and a propensity to develop hematological malignancies, mainly of myeloid origin.	Rare genetic hematologic disease
Orphanet:71493	Familial thrombocytosis	THPO;JAK2;MPL	3	Familial thrombocytosis is a type of thrombocytosis, a sustained elevation of platelet numbers, which affects the platelet/megakaryocyte lineage and may create a tendency for thrombosis and hemorrhage but does not cause myeloproliferation.	Rare genetic hematologic disease
Orphanet:71289	Radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome	MECOM;HOXA11	2	 gene (7p15).	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic hematologic disease
Orphanet:71526	Obesity due to pro-opiomelanocortin deficiency	POMC	1	Pro-opiomelanocortin (POMC) deficiency is a form of monogenic obesity resulting in severe early-onset obesity, adrenal insufficiency, red hair and pale skin.	NA
Orphanet:71528	Obesity due to prohormone convertase I deficiency	PCSK1	1	Prohormone convertase-I deficiency is the rarest form of monogenic obesity. The disorder is characterised by severe childhood obesity, hypoadrenalism, reactive hypoglycaemia, and elevated circulating levels of certain prohormones.	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility
Orphanet:71529	Obesity due to melanocortin 4 receptor deficiency	MC4R	1	Melanocortin 4 receptor (MC4R) deficiency is the commonest form of monogenic obesity identified so far. MC4R deficiency is characterised by severe obesity, an increase in lean body mass and bone mineral density, increased linear growth in early childhood, hyperphagia beginning in the first year of life and severe hyperinsulinaemia, in the presence of preserved reproductive function.	NA
Orphanet:71517	Rapid-onset dystonia-parkinsonism	ATP1A3	1	Rapid-onset dystonia-parkinsonism (RDP) is a very rare movement disorder, characterized by the abrupt onset of parkinsonism and dystonia, often triggered by physical or psychological stress.	Rare genetic neurological disorder
Orphanet:71518	Benign paroxysmal torticollis of infancy	CACNA1A	1	A rare, transient paroxysmal dystonia characterized by onset of recurrent episodes of torticollic posturing of the head between infancy and early-childhood.	Rare genetic neurological disorder
Orphanet:73229	HANAC syndrome	COL4A1	1	A rare multisystemic disease characterized by small-vessel brain disease, cerebral aneurysm, and extracerebral findings involving the kidney, muscle, and small vessels of the eye.	Rare genetic neurological disorder;Rare genetic renal disease
Orphanet:39041	Omenn syndrome	ADA;RAG1;RAG2;CHD7;DCLRE1C;IL2RG;LIG4;RMRP;IL7R	9	Omenn syndrome (OS) is an inflammatory condition characterized by erythroderma, desquamation, alopecia, chronic diarrhea, failure to thrive, lymphadenopathy, and hepatosplenomegaly, associated with severe combined immunodeficiency (SCID; see this term).	Rare genetic immune disease
Orphanet:39044	Uveal melanoma	CYSLTR2;BAP1;BAP1;GNAQ;GNA11;SF3B1	6	Uveal melanoma is a rare tumor of the eye, arising from the choroid in 90% of cases and from the iris and ciliary body in the other 10% of cases, which clinically presents with visual symptoms (including blurred vision, photopsia, floaters, and visual field reduction), a visible mass and pain. Fatal metastatic disease is seen in about half of all patients, with the liver being the most frequent site of metastasis.	
Orphanet:38874	Dihydropyrimidinuria	DPYS	1	Dihydropyrimidinase (DPD) deficiency is a very rare pyrimidine metabolism disorder with a variable clinical presentation including gastrointestinal manifestations (feeding problems, cyclic vomiting, gastroesophageal reflux, malabsorption with villous atrophy), hypotonia, intellectual deficit, seizures, and less frequently growth retardation, failure to thrive, microcephaly and autism. Asymptomatic cases are also reported. DPD deficiency increases the risk of 5-FU toxicity.	Rare inborn errors of metabolism
Orphanet:37612	Episodic ataxia type 1	KCNA1	1	Episodic ataxia type 1 (EA1) is a frequent form of Hereditary episodic ataxia (EA; see this term) characterized by brief episodes of ataxia, neuromyotonia, and continuous interictal myokymia.	Rare genetic neurological disorder
Orphanet:37553	Andersen-Tawil syndrome	KCNJ2;KCNJ5	2	A rare disorder characterized by periodic muscle paralysis, prolongation of the QT interval with a variety of ventricular arrhythmias (leading to predisposition to sudden cardiac death) and characteristic physical features: short stature, scoliosis, low-set ears, hypertelorism, broad nasal root, micrognathia, clinodactyly, brachydactyly and syndactyly.	Rare genetic neurological disorder;Rare genetic cardiac disease
Orphanet:37042	Immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome	FOXP3	1	Immunodysregulation - polyendocrinopathy - enteropathy - X-linked (IPEX) syndrome is a severe congenital systemic autoimmune disease characterized by refractory diarrhea, endocrinopathies, cutaneous involvement, and infections.	Rare genetic immune disease;Rare genetic gastroenterological disease;Rare genetic endocrine disease
Orphanet:36899	Myoclonus-dystonia syndrome	SGCE;TOR1A;DRD2;DYT15;KCTD17	5	Myoclonus-dystonia syndrome (MDS) is a rare movement disorder characterized by mild to moderate dystonia along with 'lightning-like' myoclonic jerks.	Rare genetic neurological disorder
Orphanet:41751	Bietti crystalline dystrophy	CYP4V2	1	Bietti's crystalline dystrophy (BCD) is a rare progressive autosomal recessive tapetoretinal degeneration disease, occurring in the third decade of life, characterized by small sparkling crystalline deposits in the posterior retina and corneal limbus in addition to sclerosis of the choroidal vessels and manifesting as nightblindness, decreased vision, paracentral scotoma, and, in the end stages of the disease, legal blindness.	Rare genetic eye disease
Orphanet:42062	Iminoglycinuria	SLC6A20;SLC36A2;SLC6A18;SLC6A19	4	Iminoglycinuria is a metabolic disorder resulting from defective renal tube reabsorption of proline, hydroxyproline and glycine. The prevalence is estimated at around 1 in 15 000. The disorder is usually asymptomatic and is identified fortuitously by detection of increased levels of the imino acids and glycine in the urine. It is transmitted as an autosomal recessive trait.	Rare inborn errors of metabolism
Orphanet:35706	Glutaric acidemia type 3	SUGCT	1	Glutaryl-CoA oxidase deficiency is a peroxisomal disorder leading to glutaric aciduria. The prevalence is unknown. There is no distinctive phenotype associated with this disorder and one of the reported cases was asymptomatic. Transmission appears to be autosomal recessive.	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:35704	L-Arginine:glycine amidinotransferase deficiency	GATM	1	L-Arginine:glycine amidinotransferase (AGAT) deficiency is a very rare type of creatine deficiency sydrome characterized by global developmental delay, intellectual disability, and myopathy.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:35710	Glucose-galactose malabsorption	SLC5A1	1	Glucose-galactose malabsorption (GGM) is a very rare, potentially lethal, genetic metabolic disease characterized by impaired glucose-galactose absorption resulting in severe watery diarrhea and dehydration with onset inthe neonatal period.	Rare inborn errors of metabolism;Rare genetic gastroenterological disease
Orphanet:35737	Morning glory disc anomaly	PAX6	1	A congenital optic disc anomaly characterized by a funnel shaped excavation of the posterior fundus that incorporates the optic disc. Clinically, the optic disc malformation resembles the morning glory flower. Morning glory disc anomaly (MGDA) is usually unilateral and often results in a decrease in best-corrected visual acuity (BCVA). MGDA can be isolated or associated with other ocular or non-ocular anomalies.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:35708	Aromatic L-amino acid decarboxylase deficiency	DDC	1	A very rare, severe, genetic neurometabolic disorder associated with clinical manifestations related to underproduction of serotonin and dopamine, mainly hypotonia, hypokinesia, ptosis oculogyric crises, and signs of autonomic dysfunction.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:35689	Primary lateral sclerosis	SPG7	1	Primary lateral sclerosis (PLS) is an idiopathic non-familial motor neuron disease characterized by slowly progressive upper motor neuron dysfunction leading to spasticity, mild weakness in voluntary muscle movement, hyperreflexia, and loss of motor speech production.	Rare genetic neurological disorder
Orphanet:35701	3-hydroxy-3-methylglutaryl-CoA synthase deficiency	HMGCS2	1	3-hydroxy-3-methylglutaryl-CoA synthase deficiency (HMG-CoA synthase deficiency) is a rare autosomal recessively inherited disorder of ketone body metabolism (see this term), reported in less than 20 patients to date, characterized clinically by episodes of decompensation (often associated with gastroenteritis or fasting) that present with vomiting, lethargy, hepatomegaly, non ketotic hypoglycemia and, in rare cases, coma. Patients are mostly asymptomatic between acute epidodes. HMG-CoA synthase deficiency requires an early diagnosis in order to avoid hypoglycemic crises that can lead to permanent brain damage or death.	Rare inborn errors of metabolism
Orphanet:35612	Nanophthalmos	MFRP;TMEM98;PRSS56	3	A rare ophthalmic disease and a severe form of microphthalmia (small eye phenotype) characterized by a small eye with a short axial length, severe hyperopia, an elevated lens/eye ratio, and a high incidence of angle-closure glaucoma.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:35173	X-linked dominant chondrodysplasia punctata	EBP	1	A rare genodermatosis disease with great phenotypic variation and characterized most commonly by ichthyosis following the lines of Blaschko, chondrodysplasia punctata (CDP), asymmetric shortening of the limbs, cataracts and short stature.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic skin disease;Rare genetic eye disease;Rare genetic bone disease
Orphanet:35664	ALDH18A1-related De Barsy syndrome	ALDH18A1	1	A rare, genetic, neurometabolic disease characterized by prenatal and postnatal growth retardation, hypotonia, failure to thrive, large and late-closing fontanel, development delay, cutis laxa, joint laxity, progeroid appearance, and dysmorphic facial features. In addition, corneal opacities, cataracts, myopia, seizures, hyperreflexia and athetoid movements have also been associated.	Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic eye disease;Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:35120	Hemolytic anemia due to pyrimidine 5' nucleotidase deficiency	NT5C3A	1	Hemolytic anemia due to pyrimidine 5' nucleotidase deficiency is a rare, hereditary, hemolytic anemia due to an erythrocyte nucleotide metabolism disorder characterized by mild to moderate hemolytic anemia associated with basophilic stippling and the accumulation of high concentrations of pyrimidine nucleotides within the erythrocyte. Patients present with variable features of jaundice, splenomegaly, hepatomegaly, gallstones, and sometimes require transfusions. Rare cases of mild development delay and learning difficulties are reported.	Rare inborn errors of metabolism;Rare genetic hematologic disease
Orphanet:35107	Desmosterolosis	DHCR24	1	Desmosterolosis is a very rare sterol biosynthesis disorder characterized by multiple congenital anomalies, failure to thrive, and intellectual disability, with elevated levels of desmosterol.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic bone disease
Orphanet:35099	Isolated brachycephaly	FGFR3;ZIC1;TCF12;TWIST1	4	Isolated brachycephaly is a relatively frequent nonsyndromic craniosynostosis consisting of premature fusion of both coronal sutures leading to skull deformity with a broad flat forehead and palpable coronal ridges.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease
Orphanet:35098	Isolated plagiocephaly	FGFR3;ZIC1;TCF12;TWIST1	4	Isolated synostotic plagiocephaly (SP) is a form of nonsyndromic craniosynostosis characterized by premature fusion of one coronal suture leading to skull deformity and facial asymmetry.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease
Orphanet:36387	Generalized epilepsy with febrile seizures-plus	SCN1A;SCN1B;SCN2A;SCN9A;GABRD;GABRG2;STX1B;ADGRV1	8	Generalized epilepsy with febrile seizures plus (GEFS+) is a familial epilepsy syndrome in which family members display a seizure disorder from the GEFS+ spectrum which ranges from simple febrile seizures (FS) to the more severe phenotype of myoclonic-astatic epilepsy (MAE) or Dravet syndrome (DS) (see these terms).	Rare genetic neurological disorder
Orphanet:36412	Hypocomplementemic urticarial vasculitis	DNASE1L3	1	Hypocomplementemic urticarial vasculitis (HUV) is an immune complex-mediated small vessel vasculitis characterized by urticaria and hypocomplementemia (low C1q with or without low C3 and C4), and usually associated with circulating anti-C1q autoantibodies. Arthritis, pulmonary disease, ocular inflammation, and glomerulonephritis are common systemic manifestations.	
Orphanet:36426	Stevens-Johnson syndrome	HLA-B;IKZF1	2	Stevens-Johnson syndrome is a limited form of toxic epidermal necrolysis (see this term) characterized by destruction and detachment of the skin epithelium and mucous membranes involving less than 10% of the body surface area.	
Orphanet:36355	Bleeding disorder due to P2Y12 defect	P2RY12	1	P2Y12 defect is a rare hemorrhagic disorder characterized by mild to moderate bleeding diathesis with easy bruising, mucosal bleedings, and excessive post-operative hemorrhage due to defect of the platelet P2Y12 receptor resulting in selective impairment of platelet responses to adenosine diphosphate.	Rare genetic hematologic disease
Orphanet:36367	Distal monosomy 1q	ZBTB18	1	1qter deletion syndrome is a chromosomal anomaly characterized by an intellectual deficiency, progressive microcephaly, seizures, growth delay, distinct facial dysmorphic features and various midline defects including cardiac, corpus callosum, gastro-oesophalgeal and urogenital anomalies.	Rare chromosomal anomaly
Orphanet:36383	COL4A1-related familial vascular leukoencephalopathy	COL4A1	1	COL4A1-related familial vascular leukoencephalopathy is a rare, genetic, neurological disease characterized by the presence of fragile small-vessel intracerebral vasculature in various members of a single family, manifesting, clinically, with single or recurrent hemorrhagic and/or ischemic stroke and, frequently, ocular and renal involvement. Neuroimaging reveals diffuse, periventricular leukoencephalopathy associated with dilated perivascular spaces, lacunar infarction and microhemorrhages.	Rare genetic neurological disorder
Orphanet:36386	Hereditary sensory and autonomic neuropathy type 1	ATL1;SPTLC1;SPTLC2;ATL3	4	Hereditary sensory neuropathy type I (HSN I) is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:35878	Hyperinsulinism-hyperammonemia syndrome	GLUD1	1	Hyperinsulinism-hyperammonemia syndrome (HIHA) is a frequent form of diazoxide-sensitive diffuse hyperinsulinism (see this term), characterized by an excessive/ uncontrolled insulin secretion (inappropriate for the level of glycemia), asymptomatic hyperammonemia and recurrent episodes of profound hypoglycemia induced by fasting and protein rich meals, requiring rapid and intensive treatment to prevent neurological sequelae. Epilepsy and cognitive deficit that are unrelated to hypoglycemia may also occur.	Rare inborn errors of metabolism;Rare genetic endocrine disease;Rare genetic developmental defect during embryogenesis
Orphanet:35858	Imerslund-Gräsbeck syndrome	AMN;CUBN	2	Imerslund-Grasbeck syndrome (IGS) or selective vitamin B12 (cobalamin) malabsorption with proteinuria is a rare autosomal recessive disorder characterized by vitamin B12 deficiency commonly resulting in megaloblastic anemia, which is responsive to parenteral vitamin B12 therapy and appears in childhood.	Rare inborn errors of metabolism;Rare genetic renal disease;Rare genetic hematologic disease;Rare genetic gastroenterological disease
Orphanet:35909	Combined deficiency of factor V and factor VIII	MCFD2;LMAN1	2	Combined deficiency of factor V and factor VIII is an inherited bleeding disorder due to the reduction in activity and antigen levels of both factor V (FV) and factor VIII (FVIII) and characterized by mild-to-moderate bleeding symptoms.	Rare genetic hematologic disease
Orphanet:33572	5-oxoprolinase deficiency	OPLAH	1	A very heterogeneous condition characterized by 5-oxoprolinuria.	Rare inborn errors of metabolism
Orphanet:33445	Neuroectodermal melanolysosomal disease	MYO5A	1	Elejalde syndrome (ES) is characterized by silvery to leaden hair, bronze skin colour in sun-exposed areas and severe neurological impairment.	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic skin disease;Rare genetic neurological disorder
Orphanet:33402	Pediatric hepatocellular carcinoma	MET;CTNNB1	2	A rare, aggressive and malignant hepatic tumor arising from the hepatocytes. It develops mainly in children over 10 years of age, either in a cirrhotic background, or more commonly in a non-cirrhotic background (70% of cases).	
Orphanet:34217	Naxos disease	JUP	1	A recessively inherited condition with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) and a cutaneous phenotype, characterised by peculiar woolly hair and palmoplantar keratoderma.	Rare genetic cardiac disease;Rare genetic skin disease
Orphanet:33574	Glutamate-cysteine ligase deficiency	GCLC	1	A disorder that is principally characterized by hemolytic anemia, (usually rather mild), however, the presence of neurological symptoms has also been reported.	Rare inborn errors of metabolism;Rare genetic hematologic disease
Orphanet:33573	Gamma-glutamyl transpeptidase deficiency	GGT1	1	A disorder that is characterized by increased glutathione concentration in the plasma and urine.	Rare inborn errors of metabolism
Orphanet:33110	Autosomal agammaglobulinemia	IGHM;IGLL1;LRRC8A;TCF3;CD79A;CD79B;BLNK;PIK3R1	8	A rare form of agammaglobulinemia, a primary immunodeficiency disease, and is characterized by variable immune dysfunction with frequent and recurrent bacterial infections and/or chronic diarrhea.	Rare genetic immune disease
Orphanet:33108	Lethal multiple pterygium syndrome	NEB;RAPSN;RYR1;CHRNA1;CHRND;CHRNG	6	A rare genetic multiple pterygium syndrome characterized by intrauterine growth retardation, fetal akinesia, multiple joint contractures causing severe arthrogryposis and pterygia (webbing) across multiple joints. Cystic hygroma and/or fetal hydrops are almost invariably present.	Rare genetic developmental defect during embryogenesis
Orphanet:33067	Metaphyseal chondrodysplasia, Jansen type	PTH1R	1	Jansen's metaphyseal chondrodysplasia (JMC) is a very rare autosomal dominant skeletal dysplasia characterized by short-limbed short stature (due to severe metaphyseal changes that are often discovered in childhood by imaging), waddling gait, bowed legs, contracture deformities of the joints, short hands with clubbed fingers, clinodactyly, prominent upper face and small mandible, as well as chronic parathyroid hormone-independent hypercalcemia, hypercalciuria, and mild hypophosphatemia.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:33069	Dravet syndrome	SCN1A;SCN1B;SCN9A;GABRA1;GABRG2;STXBP1;PCDH19;SCN2A	8	Dravet syndrome (DS) is a genetic epilepsy of childhood characterized by a variety of drug-resistant seizures often induced by fever, presenting in previously healthy children, and which frequently leads to cognitive and motor impairment.	Rare genetic neurological disorder
Orphanet:33001	Lymphedema-distichiasis syndrome	FOXC2	1	Lymphedema - distichiasis is a rare syndromic lymphedema disorder characterized by lower-limb lymphedema and varying degrees of abnormal growth of eyelashes from the orifices of the Meibomian glands (distichiasis), with occasional associated manifestations.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:33355	Reticular dysgenesis	AK2	1	Reticular dysgenesis is the most severe form of severe combined immunodeficiency (SCID; see this term) and is characterized by bilateral sensorineural deafness and a lack of innate and adaptive immune functions leading to fatal septicemia within days after birth if not treated.	Rare genetic immune disease
Orphanet:33364	Trichothiodystrophy	MPLKIP;ERCC2;GTF2H5;ERCC3;RNF113A;GTF2E2	6	Trichothiodystrophy or TTD is a heterogeneous group disorders characterized by short, brittle hair with low-sulphur content (due to an abnormal synthesis of the sulphur containing keratins).	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Genetic infertility
Orphanet:33226	Waldenström macroglobulinemia	MYD88	1	Waldenström macroglobulinemia (WM) is an indolent B-cell lymphoproliferative disorder characterized by the accumulation of monoclonal cells in the bone marrow and peripheral lymphoid tissues, and associated with the production of serum immunoglobulin M (IgM) monoclonal protein.	
Orphanet:35069	Infantile neuroaxonal dystrophy	PLA2G6	1	Infantile neuroaxonal dystrophy/atypical neuroaxonal dystrophy (INAD/atypical NAD) is a type of neurodegeneration with brain iron accumulation (NBIA; see this term) characterized by psychomotor delay and regression, increasing neurological involvement with symmetrical pyramidal tract signs and spastic tetraplegia. INAD may be classic or atypical and patients present with symptoms anywhere along a continuum between the two.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:35093	Isolated scaphocephaly	ALX4;ERF;TWIST1	3	Isolated scaphocephaly is a form of nonsyndromic craniosynostosis characterized by premature fusion of the sagittal suture.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease
Orphanet:35078	T-B+ severe combined immunodeficiency due to JAK3 deficiency	JAK3	1	Severe combined immunodeficiency (SCID) T-B+ due to JAK3 deficiency is a form of SCID (see this term) characterized by severe and recurrent infections, associated with diarrhea and failure to thrive.	Rare genetic immune disease
Orphanet:34520	Congenital muscular dystrophy with integrin alpha-7 deficiency	ITGA7	1	Congenital muscular dystrophy with integrin alpha-7 deficiency is a rare, genetic, congenital muscular dystrophy due to extracellular matrix protein anomaly characterized by early motor development delay and muscle weakness with mild elevation of serum creatine kinase, that may be followed by progressive disease course with predominantly proximal muscle weakness and atrophy, motor development regress, scoliosis and respiratory insufficiency.	Rare genetic neurological disorder
Orphanet:34514	Autosomal recessive limb-girdle muscular dystrophy type 2G	TCAP	1	A mild subtype of autosomal recessive limb-girdle muscular dystrophy characterized by a variable onset (ranging from infancy to adolescence) of progressive proximal upper and lower limb muscle weakness and atrophy. Mild scapular winging, calf hypertrophy, and lack of respiratory and cardiac involvement are also observed.	Rare genetic neurological disorder
Orphanet:34515	Autosomal recessive limb-girdle muscular dystrophy type 2I	FKRP	1	A subtype of autosomal recessive limb-girdle muscular dystrophy that presents a highly variable age of onset and phenotypic spectrum typically characterized by slowly progressive proximal weakness of the pelvic and shoulder girdle musculature (predominantly affecting the lower limbs), frequently associated with waddling gait, scapular winging, calf and tongue hypertrophy, exercise-induced myalgia, and myoglobinuria and/or elevated creatine kinase serum levels. Abdominal muscle weakness, cardiomyopathy, respiratory muscle involvement and various brain abnormalities have also been reported.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:34516	Autosomal dominant limb-girdle muscular dystrophy type 1D	DNAJB6	1	A subtype of autosomal dominant limb-girdle muscular dystrophy characterized by an adult-onset of slowly progressive, proximal pelvic girdle weakness, with none, or only minimal, shoulder girdle involvement, and absence of cardiac and respiratory symptoms. Mild to moderate elevated creatine kinase serum levels and gait abnormalities are frequently observed.	Rare genetic neurological disorder
Orphanet:34517	Autosomal dominant limb-girdle muscular dystrophy type 1E	DES	1	NA	Rare genetic neurological disorder
Orphanet:34587	Glycogen storage disease due to LAMP-2 deficiency	LAMP2	1	Glycogen storage disease due to LAMP-2 (Lysosomal-Associated Membrane Protein 2) deficiency is a lysosomal glycogen storage disease characterised by severe cardiomyopathy and variable degrees of muscle weakness, frequently associated with intellectual deficit.	Rare genetic cardiac disease;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:34592	Immunodeficiency by defective expression of MHC class I	TAP2;TAP1;TAPBP;B2M	4	Immunodeficiency by defective expression of HLA class 1 is a very rare, primary, genetic, immunodeficiency disorder characterized by partial or complete absence of human leukocyte antigen class I expression resulting in a non-specific clinical picture of impaired immune response and susceptibility to infections.	Rare genetic immune disease
Orphanet:34527	Familial primary hypomagnesemia with normocalciuria and normocalcemia	EGF;CNNM2	2	A form of familial primary hypomagnesemia (FPH), characterized by low serum magnesium (Mg) values but inappropriate normal urinary Mg values (i.e. renal hypomagnesemia). The typical symptoms are weakness of the limbs, vertigo, headaches, seizures, brisk tendon reflexes and mild to moderate psychomotor delay.	Rare genetic renal disease;Rare inborn errors of metabolism
Orphanet:34528	Autosomal dominant primary hypomagnesemia with hypocalciuria	FXYD2;HNF1B	2	A mild form of familial primary hypomagnesemia (FPH), characterized by extreme weakness, tetany and convulsions. Secondary disturbances in calcium excretion are observed.	Rare genetic renal disease;Rare inborn errors of metabolism
Orphanet:32960	Tumor necrosis factor receptor 1 associated periodic syndrome	TNFRSF1A	1	Tumor necrosis factor receptor 1 associated periodic syndrome (TRAPS) is a periodic fever syndrome, characterized by recurrent fever, arthralgia, myalgia and tender skin lesions lasting for 1 to 3 weeks, associated with skin, joint, ocular and serosal inflammation and complicated by secondary amyloidosis (see this term).	Rare genetic immune disease;Rare genetic systemic or rheumatologic disease
Orphanet:52530	Pseudo-von Willebrand disease	GP1BA	1	Platelet type Von Willebrand disease (PT-VWD) is a bleeding disorder characterized by mild to moderate mucocutaneous bleeding, which becomes more pronounced during pregnancy or following ingestion of drugs that have anti-platelet activity. PT-VWD is due to hyperresponsive platelets, resulting in thrombocytopenia.	Rare genetic hematologic disease
Orphanet:52688	Myelodysplastic syndrome	MECOM;GATA2	2	NA	NA
Orphanet:52429	Branchiootic syndrome	EYA1;SIX1	2	Branchiootic syndrome is a rare, genetic multiple congenital anomalies syndrome characterized by second branchial arch anomalies (branchial cysts and fistulae), malformations of the outer, middle and inner ear associated with sensorineural, mixed or conductive hearing loss, and the absence of renal abnormalities. Typical ear findings consist of malformed auricles (e.g. lop or cupped ears), preauricular pits and/or tags, and middle and/or inner ear dysplasias (inculding cochlear, vestibular and semicircular channel hypoplasia, malformation of the ossicles and of middle ear space).	Genetic otorhinolaryngologic disease;Rare genetic developmental defect during embryogenesis
Orphanet:52503	X-linked creatine transporter deficiency	SLC6A8	1	X-linked creatine transporter deficiency (CRTR-D) is a creatine deficiency syndrome characterized clinically by global developmental delay/ intellectual disability (DD/ID) with prominent speech/language delay, autistic behavior and seizures.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:52430	Inclusion body myopathy with Paget disease of bone and frontotemporal dementia	VCP;HNRNPA2B1;HNRNPA1	3	Inclusion body myopathy with Paget disease of bone and frontotemporal dementia (IBMPFD) is a multisystem degenerative genetic disorder characterized by adult-onset proximal and distal muscle weakness (clinically resembling limb-girdle muscular dystrophy; see this term); early-onset Paget disease of bone (see this term), manifesting with bone pain, deformity and enlargement of the long-bones; and premature frontotemporal dementia (see this term), manifesting first with dysnomia, dyscalculia and comprehension deficits followed by progressive aphasia, alexia, and agraphia. As the disease progresses, muscle weakness begins to affect the other limbs and respiratory muscles, ultimately resulting in respiratory or cardiac failure.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic neurological disorder
Orphanet:52416	Mantle cell lymphoma	CCND1;ATM;IGH	3	Mantle cell lymphoma is a rare form of malignant non-Hodgkin lymphoma (see this term) affecting B lymphocytes in the lymph nodes in a region called the ``mantle zone''.	
Orphanet:52427	Retinitis punctata albescens	PRPH2;RDH5;RHO;RLBP1	4	NA	Rare genetic eye disease
Orphanet:52417	MALT lymphoma	MALT1;BIRC3;IGH;FOXP1;BCL10	5	MALT (mucosa-associated lymphoid tissue) lymphoma is a rare form of malignant non-Hodgkin lymphoma (see this term) that affects B cells and grows at the expense of lymphoid tissue associated with mucous membranes, but also occurs, more rarely, in lymph nodes.	
Orphanet:52055	Corpus callosum agenesis-intellectual disability-coloboma-micrognathia syndrome	IGBP1	1	Corpus callosum agenesis-intellectual disability-coloboma-micrognathia syndrome is a developmental anomalies syndrome characterized by coloboma of the iris and optic nerve, facial dysmorphism (high forehead, microretrognathia, low-set ears), intellectual deficit, agenesis of the corpus callosum (ACC), sensorineural hearing loss, skeletal anomalies and short stature.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:52368	Mohr-Tranebjaerg syndrome	TIMM8A	1	An X-linked syndromic intellectual disability characterized by clinical manifestations commencing with early childhood onset hearing loss, followed by adolescent onset progressive dystonia or ataxia, visual impairment from early adulthood onwards and dementia from the 4th decade onwards.	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:53271	Muenke syndrome	FGFR3	1	Muenke syndrome is a syndromic craniosynostosis with significant phenotypic variability, usually characterized by coronal synostosis, midfacial retrusion, strabismus, hearing loss and developmental delay.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:53347	Brody myopathy	ATP2A1	1	NA	Rare genetic neurological disorder
Orphanet:53035	Caroli disease	PKHD1	1	Caroli disease (CD) is a rare congenital liver disease characterized by non-obstructive cystic dilatations of the intra-hepatic and rarely extra-hepatic bile ducts.	Rare genetic hepatic disease;Rare genetic developmental defect during embryogenesis
Orphanet:52901	Isolated follicle stimulating hormone deficiency	FSHB	1	NA	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility
Orphanet:53690	Congenital lactase deficiency	LCT	1	Congenital lactase deficiency is a rare severe gastrointestinal disorder in newborns primarily reported in Finland and characterized clinically by watery diarrhea on feeding with breast-milk or lactose-containing formula.	Rare inborn errors of metabolism;Rare genetic gastroenterological disease
Orphanet:53689	Congenital chloride diarrhea	SLC26A3	1	NA	Rare genetic gastroenterological disease
Orphanet:53583	Paroxysmal dystonic choreathetosis with episodic ataxia and spasticity	SLC2A1	1	A rare, genetic, paroxysmal dystonia disorder characterized by childhood to adolescent-onset of episodic paroxysmal choreoathetosis, triggered mainly by sudden movements, prolonged exercise, anxiety and emotional stress, in association with progressive spastic paraparesis (onest in adulthood), gait ataxia, mild to moderate cognitive impairment, and/or epileptic seizures. Episodes typically last from a few minutes to hours, have a variable frequency (daily to yearly), and are relieved by rest. Frequency of episodes tends to decrease with age.	Rare genetic neurological disorder
Orphanet:53540	Goldmann-Favre syndrome	NR2E3	1	Goldmann-Favre syndrome (GFS) is a vitreoretinal dystrophy characterized by early onset of night blindness, reduced bilateral visual acuity, and typical fundus findings (progressive pigmentary degenerative changes, macular edema, retinoschisis).	Rare genetic eye disease
Orphanet:53351	X-linked dystonia-parkinsonism	TAF1	1	X-linked dystonia-parkinsonism (XDP) is a neurodegenerative movement disorder characterized by adult-onset parkinsonism that is frequently accompanied by focal dystonia, which becomes generalized over time, and that has a highly variable clinical course.	Rare genetic neurological disorder
Orphanet:54260	Left ventricular noncompaction	PLEKHM2;PKP2;ACTC1;TNNT2;TPM1;DTNA;MYBPC3;MYH7;LDB3;LMNA;MIB1;PRDM16;MYH7B;MIB2	14	Left ventricular noncompaction (LVNC) is a rare cardiomyopathy characterized anatomically by prominent left ventricular trabeculae and deep intratrabecular recesses causing progressive systolic and diastolic dysfunction, conduction abnormalities, and occasionally thromboembolic events.	Rare genetic cardiac disease;Laminopathy
Orphanet:53698	Hyaline body myopathy	MYH7	1	NA	Rare genetic neurological disorder
Orphanet:53696	Lethal arthrogryposis-anterior horn cell disease syndrome	GLE1	1	NA	Rare genetic developmental defect during embryogenesis
Orphanet:53697	Gnathodiaphyseal dysplasia	ANO5	1	Gnathodiaphyseal dysplasia (GDD) is a bone dysplasia characterized by bone fragility, frequent bone fractures at a young age, cemento-osseous lesions of the jaw bones, bowing of tubular bones (tibia and fibula) and diaphyseal sclerosis of long bones associated with generalized osteopenia. GD follows an autosomal dominant mode of transmission.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:53691	Congenital cornea plana	KERA	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:53693	GRACILE syndrome	BCS1L	1	GRACILE syndrome is an inherited lethal mitochondrial disorder characterized by fetal growth restriction (GR), aminoaciduria (A), cholestasis (C), iron overload (I), lactacidosis (L), and early death (E).	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic hepatic disease
Orphanet:48818	Aceruloplasminemia	CP	1	A rare adult-onset disorder of neurodegeneration with brain iron accumulation (NBIA) characterized by anemia, retinal degeneration, diabetes and various neurological symptoms.	Rare genetic eye disease;Rare inborn errors of metabolism;Rare genetic neurological disorder;Rare genetic hematologic disease
Orphanet:49382	Achromatopsia	PDE6C;RPGR;CNGA3;CNGB3;PDE6H;GNAT2;ATF6	7	A rare autosomal recessive retinal disorder characterized by color blindness, nystagmus, photophobia, and severely reduced visual acuity due to the absence or impairment of cone function.	Rare genetic eye disease
Orphanet:48431	Congenital cataracts-facial dysmorphism-neuropathy syndrome	CTDP1	1	Congenital Cataracts Facial Dysmorphism Neuropathy (CCFDN) syndrome is a complex developmental disorder of autosomal recessive inheritance.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:48652	Monosomy 22q13.3	SHANK3	1	Monosomy 22q13.3 syndrome (deletion 22q13.3 syndrome or Phelan-McDermid syndrome) is a chromosome microdeletion syndrome characterized by neonatal hypotonia, global developmental delay, normal to accelerated growth, absent to severely delayed speech, and minor dysmorphic features.	Rare chromosomal anomaly
Orphanet:50814	Craniolenticulosutural dysplasia	SEC23A	1	Craniolenticulosutural dysplasia (CLSD), also known as Boyadjiev-Jabs syndrome, is characterized by the specific association of large and late-closing fontanels, hypertelorism, early-onset cataract and mild generalized skeletal dysplasia.	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:49827	Thiamine-responsive megaloblastic anemia syndrome	SLC19A2	1	Thiamine-responsive megaloblastic anemia (TRMA) is characterized by a triad of megaloblastic anemia, non-type I diabetes mellitus, and sensorineural deafness.	Genetic otorhinolaryngologic disease;Rare genetic endocrine disease;Rare inborn errors of metabolism;Rare genetic hematologic disease
Orphanet:50945	Blomstrand lethal chondrodysplasia	PTH1R	1	Blomstrand lethal chondrodysplasia (BLC) is a neonatal osteosclerotic dysplasia (see this term) characterized by advanced endochondral bone maturation, very short limbs, dwarfism and prenatal lethality.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:50944	Schöpf-Schulz-Passarge syndrome	WNT10A	1	Schöpf-Schulz-Passarge syndrome (SSPS) is a rare autosomal recessive ectodermal dysplasia characterized by multiple eyelid apocrine hidrocystomas, palmoplantar keratoderma, hypotrichosis, hypodontia and nail dystrophy.	Inherited cancer-predisposing syndrome;Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:51083	Familial short QT syndrome	KCNJ2;KCNH2;KCNQ1;CACNA2D1	4	Familial short QT syndrome is a newly described cardiologic entity that associates a short QT interval (QT and QTc 300 ms) on the surface electrocardiogram (ECG) with a high risk of syncope or sudden death due to malignant ventricular arrhythmia.	Rare genetic cardiac disease
Orphanet:50943	Keratolytic winter erythema	CTSB	1	Keratolytic winter erythema is a rare epidermal disease, characterized by recurrent centrifugal palmoplantar peeling and erythema presenting seasonal variation (cold weather). Skin lesions may spread to the dorsum of hands and feet and to the interdigital spaces. Lower legs, knees and thighs may also be involved. Episodes may be preceded by itch and hyperhidrosis. Skin biopsy reveals an epidermal spongiosis with clefting in the stratum corneum, followed by regrowth. Keratolytic winter erythema follows an autosomal dominant mode of transmission.	Rare genetic skin disease
Orphanet:50942	Striate palmoplantar keratoderma	DSP;KRT1;DSG1	3	Striate palmoplantar keratoderma is an isolated, focal, hereditary palmoplantar keratoderma characterized by linear hyperkeratosis along the flexor aspect of the fingers and on palms, as well as focal hyperkeratosis of the plantar skin. Patients present with painful thickening of the skin on palms and soles, with occasional fissuring, blistering and hyperhidrosis. Rarely, hyperkeratosis on other areas may be seen (knees, dorsal aspects of the digits). Histopatologically, widened intercellular spaces between keratinocytes are observed.	Rare genetic skin disease
Orphanet:52022	Potocki-Shaffer syndrome	ALX4;EXT2;PHF21A	3	Potocki-Shaffer syndrome is characterized by multiple exostoses, parietal foramina, enlargement of the anterior fontanelle and occasionally intellectual deficit and mild cranio-facial anomalies. To date, 23 individuals from 14 families have been reported. The syndrome is caused by contiguous gene deletions on the short arm of chromosome 11 (11p11.2).	Rare genetic developmental defect during embryogenesis;Rare chromosomal anomaly
Orphanet:51608	Generalized arterial calcification of infancy	ABCC6;ENPP1	2	A rare genetic vascular disease characterized by early onset (between in utero to infancy) of extensive calcification and stenosis of the large and medium sized arteries. Presentation is typically with respiratory distress, congestive heart failure and systemic hypertension.	
Orphanet:51188	Ethylmalonic encephalopathy	ETHE1	1	Ethylmalonic acid encephalopathy (EE) is defined by elevated excretion of ethylmalonic acid (EMA) with recurrent petechiae, orthostatic acrocyanosis and chronic diarrhoea associated with neurodevelopmental delay, psychomotor regression and hypotonia with brain magnetic resonance imaging (MRI) abnormalities.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:51208	Formiminoglutamic aciduria	FTCD	1	A rare disorder of folate metabolism and transport characterized, biochemically, by elevated formiminoglutamate in urine and plasma due to glutamate formiminotransferase deficiency, associated with a highly variable clinical phenotype, ranging from developmental delay, intellectual disability and anemia to normal development without anemia. Increased hydantoin-5-propionic acid and/or folate in plasma may also be associated.	Rare inborn errors of metabolism;Rare genetic hematologic disease
Orphanet:51636	WHIM syndrome	CXCR4	1	WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome is a congenital autosomal dominant immune deficiency characterized by abnormal retention of mature neutrophils in the bone marrow (myelokathexis) and occasional hypogammaglobulinemia, associated with an increased risk for bacterial infections and a susceptibility to human papillomavirus (HPV) induced lesions (cutaneous warts, genital dysplasia and invasive mucosal carcinoma).	Rare genetic immune disease
Orphanet:42665	Tietz syndrome	MITF	1	Tietz syndrome is a genetic hypopigmentation and deafness syndrome characterized by congenital profound bilateral sensorineural hearing loss and generalized albino-like hypopigmentation of skin, eyes and hair.	Genetic otorhinolaryngologic disease;Rare genetic skin disease
Orphanet:43115	Hereditary myopathy with lactic acidosis due to ISCU deficiency	ISCU	1	A rare disease characterised by myopathy with severe exercise intolerance and deficiencies of skeletal muscle succinate dehydrogenase and aconitase.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:45448	Miyoshi myopathy	DYSF	1	A recessive distal myopathy characterized by weakness in the distal lower extremity posterior compartment (gastrocnemius and soleus muscles) and associated with difficulties in standing on tip toes.	Rare genetic neurological disorder
Orphanet:44890	Gastrointestinal stromal tumor	SDHA;SDHB;SDHC;KIT;KIT;PDGFRA	6	Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal (GI) tract, typically presenting in adults over the age of 40 (mean age 63), and only rarely in children, in various regions of the GI tract, most commonly the stomach or small intestine but also less commonly in the esophagus, appendix, rectum and colon. GISTs can be asymptomatic or present with various non-specific signs, depending on the location and size of tumor, such as loss of appetite, anemia, weight loss, fatigue, abdominal discomfort or fullness, nausea, vomiting, as well as an abdominal mass, blood in stool, and intestinal obstruction. GISTs can also be seen in familial syndromes such as Carney triad and neurofibromatosis type 1.	Rare genetic tumor
Orphanet:45358	Congenital fibrosis of extraocular muscles	PHOX2A;KIF21A;TUBB3;TUBB2B	4	NA	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:46348	Paroxysmal extreme pain disorder	SCN10A;SCN11A;SCN9A	3	A rare, genetic, neurological disorder characterized by severe episodic perirectal pain accompanied by skin flushing that is typically precipitated by defecation. Ocular and submaxillary pain, associated with triggers including cold or other irritants, may become more prominent with age.	
Orphanet:46059	Lathosterolosis	SC5D	1	Lathosterolosis is an extremely rare inborn error of sterol biosynthesis characterized by facial dysmorphism, congenital anomalies (including limb and kidney anomalies), failure to thrive, developmental delay and liver disease.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:47044	Hereditary papillary renal cell carcinoma	MET	1	Hereditary papillary renal cell carcinoma (HPRCC) is a familial renal cancer syndrome characterised by a predisposition for developing bilateral and multifocal type 1 papillary renal carcinomas.	Inherited cancer-predisposing syndrome
Orphanet:46627	Char syndrome	TFAP2B	1	A rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by the triad of patent ductus arteriosus (PDA), facial dysmorphism (wide-set eyes, downslanting palpebral fissures, mild ptosis, flat midface, flat nasal bridge and upturned nasal tip, short philtrum with a triangular mouth, and thickened, everted lips) and hand anomalies (aplasia or hypoplasia of the middle phalanges of the fifth fingers).	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:46532	Hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome	HBB;HBG1;HBG2;KLF1	4	Hereditary persistence of fetal hemoglobin (HPFH) associated with beta-thalassemia (see this term) is characterized by high hemoglobin (Hb) F levels and an increased number of fetal-Hb-containing-cells.	Rare genetic hematologic disease
Orphanet:47045	Familial cold urticaria	NLRP3;NLRC4	2	Familial cold urticaria (FCAS) is the mildest form of cryopyrin-associated periodic syndrome (CAPS; see this term) and is characterized by recurrent episodes of urticaria-like skin rash triggered by exposure to cold associated with low-grade fever, general malaise, eye redness and arthralgia/myalgia.	Rare genetic systemic or rheumatologic disease;Rare genetic immune disease
Orphanet:90050	Retinopathy of prematurity	LRP5;FZD4;NDP	3	A rare retinal vasoproliferative disease affecting preterm infants characterized initially by a delay in physiologic retinal vascular development and compromised physiologic vascularity, and subsequently by aberrant angiogenesis in the form of intravitreal neovascularization.	
Orphanet:90045	Hereditary folate malabsorption	SLC46A1	1	Hereditary folate malabsorption (HFM) is an inherited disorder of folate transport characterized by a systemic and central nervous system (CNS) folate deficiency manifesting as megaloblastic anemia, failure to thrive, diarrhea and/or oral mucositis, immunologic dysfunction and neurological disorders.	Rare genetic immune disease;Rare inborn errors of metabolism;Rare genetic gastroenterological disease;Rare genetic hematologic disease
Orphanet:90039	Hemoglobin D disease	HBB	1	Hemoglobin D disease(HbD) is a hemoglobinopathy characterized by production of abnormal variant hemoglobin known as hemoglobin D, with no or mild clinical manifestations (splenomegaly, very mild anemia).	Rare genetic hematologic disease
Orphanet:90044	Familial pseudohyperkalemia	ABCB6	1	 potassium levels in samples stored below 37°C. FP is not associated with additional hematological abnormalities, although affected individuals may show some mild abnormalities like macrocytosis.	Rare genetic hematologic disease
Orphanet:90042	Primary familial polycythemia	EPOR	1	Primary familial polycythemia is an inherited hematological disorder resulting from mutations in the erythropoietin (EPO) receptor and is characterized by an elevated absolute red blood cell mass caused by uncontrolled red blood cell production in the presence of low EPO levels.	Rare genetic hematologic disease
Orphanet:90024	Deafness with labyrinthine aplasia, microtia, and microdontia	FGF3	1	Deafness with labyrinthine aplasia, microtia, and microdontia (LAMM) is a genetic transmission deafness syndrome.	Genetic otorhinolaryngologic disease
Orphanet:90023	Primary immunodeficiency syndrome due to LAMTOR2 deficiency	LAMTOR2	1	 infections.	Rare genetic immune disease
Orphanet:90020	Amyotrophic lateral sclerosis-parkinsonism-dementia complex	PARK7;TRPM7	2	NA	
Orphanet:90031	Non-spherocytic hemolytic anemia due to hexokinase deficiency	HK1	1	, the gene that encodes red blood cell-specific hexokinase-R.	Rare genetic hematologic disease
Orphanet:90026	Primary erythromelalgia	SCN9A;SCN10A;SCN11A	3	Primary erythermalgia is characterized by intermittent attacks of red, warm, painful burning extremities. It spontaneously arises during early childhood and adolescence in the absence of any detectable underlying disorder.	Rare genetic neurological disorder
Orphanet:90030	Hemolytic anemia due to glutathione reductase deficiency	GSR	1	Haemolytic anaemia due to glutathione reductase (GSR) deficiency is characterised by nearly complete absence of GSR activity in erythrocytes.	Rare genetic hematologic disease
Orphanet:89936	X-linked hypophosphatemia	PHEX	1	X-linked hypophosphatemia (XLH) is a hereditary renal phosphate-wasting disorder characterized by hypophosphatemia, rickets and/or osteomalacia, and diminished growth.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic endocrine disease;Rare genetic renal disease
Orphanet:89844	Lissencephaly syndrome, Norman-Roberts type	RELN	1	Lissencephaly syndrome, Norman-Roberts type is characterised by the association of lissencephaly type I with craniofacial anomalies (severe microcephaly, a low sloping forehead, a broad and prominent nasal bridge and widely set eyes) and postnatal growth retardation.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:89843	Dystrophic epidermolysis bullosa pruriginosa	COL7A1	1	Dystrophic epidermolysis bullosa pruriginosa is a rare subtype of dystrophic epidermolysis bullosa (DEB, see this term) characterized by generalized or localized skin lesions associated with severe, if not intractable, pruritus.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:89842	Recessive dystrophic epidermolysis bullosa, generalized intermediate	COL7A1	1	Recessive dystrophic epidermolysis bullosa (RDEB)-generalized other, also known as RDEB non-Hallopeau-Siemens type, is a subtype of DEB (see this term) characterized by generalized cutaneous and mucosal blistering that is not associated with severe deformities.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:89841	Centripetalis recessive dystrophic epidermolysis bullosa	COL7A1	1	Centripetalis recessive dystrophic epidermolysis bullosa (RDEB-Ce) is an extremely rare subtype of dystrophic epidermolysis bullosa (DEB, see this term), characterized by blistering which begins acrally and then progressively spreads toward the trunk.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:89839	Epidermolysis bullosa simplex superficialis	COL7A1	1	Epidermolysis bullosa simplex superficialis (EBSS) is a suprabasal subtype of epidermolysis bullosa simplex (EBS, see this term) characterized by generalized or acral superficial erosions in the absence of blisters.	Rare genetic skin disease
Orphanet:89938	Infantile Bartter syndrome with sensorineural deafness	BSND;CLCNKB;CLCNKA	3	Infantile Bartter syndrome with deafness, a phenotypic variant of Bartter syndrome (see this term) is characterized by maternal polyhydramnios, premature delivery, polyuria and sensorineural deafness and is associated with hypokalemic alkalosis, increased levels of plasma renin and aldosterone, low blood pressure, and vascular resistance to angiotensin II.	Genetic otorhinolaryngologic disease;Rare genetic renal disease
Orphanet:89937	Autosomal dominant hypophosphatemic rickets	FGF23	1	A rare hereditary renal phosphate-wasting disorder characterized by hypophosphatemia, rickets and/or osteomalacia.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic endocrine disease;Rare genetic renal disease
Orphanet:90340	Blau syndrome	NOD2	1	Blau syndrome (BS) is a rare systemic inflammatory disease characterized by early onset granulomatous arthritis, uveitis and skin rash. BS now refers to both the familial and sporadic (formerly early-onset sarcoidosis) form of the same disease. The proposed term pediatric granulomatous arthritis is currently questioned since it fails to represent the systemic nature of the disease.	Rare genetic eye disease;Rare genetic skin disease;Rare genetic immune disease
Orphanet:90342	Xeroderma pigmentosum variant	POLH	1	Xeroderma pigmentosum variant is a milder subtype of xeroderma pigmentosum (XP; see this term), a rare genetic photodermatosis characterized by severe sun sensitivity and an increased risk of skin cancer.	Inherited cancer-predisposing syndrome;Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic eye disease
Orphanet:90348	Autosomal dominant cutis laxa	ALDH18A1;FBLN5;ELN	3	A rare connective tissue disorder characterized by wrinkled, redundant and sagging inelastic skin associated in some cases with internal organ involvement.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:90349	Autosomal recessive cutis laxa type 1	EFEMP2;FBLN5	2	A generalized connective tissue disorder characterized by the association of wrinkled, redundant and sagging inelastic skin with severe systemic manifestations (lung atelectesias and emphysema, vascular anomalies, and gastrointestinal and genitourinary tract diverticuli).	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:90354	Brittle cornea syndrome	ZNF469;PRDM5	2	Brittle cornea syndrome is a form of Ehlers-Danlos syndrome characterized by a severe ocular manifestations due to extreme corneal thinning and fragility with rupture in the absence of significant trauma, and progression to blindness. Extraocular manifestations comprise deafness, developmental hip dysplasia, and joint hypermobility.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic systemic or rheumatologic disease
Orphanet:90308	Klippel-Trénaunay syndrome	AGGF1	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic eye disease;Rare genetic bone disease
Orphanet:90307	Parkes Weber syndrome	RASA1	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease;Rare genetic eye disease;Rare genetic bone disease
Orphanet:90318	OBSOLETE: Ehlers-Danlos syndrome type 2	COL5A1;COL5A2;COL1A1	3	NA	NA
Orphanet:90309	OBSOLETE: Ehlers-Danlos syndrome type 1	COL5A2;COL1A1;COL5A1	3	NA	NA
Orphanet:90322	Cockayne syndrome type 2	ERCC6;ERCC8;ERCC1	3	NA	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder;Inherited cancer-predisposing syndrome;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic skin disease
Orphanet:90321	Cockayne syndrome type 1	ERCC4;ERCC6;ERCC8	3	NA	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder;Inherited cancer-predisposing syndrome;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic skin disease
Orphanet:90324	Cockayne syndrome type 3	ERCC6;ERCC8	2	NA	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder;Inherited cancer-predisposing syndrome;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic skin disease
Orphanet:90153	Mandibuloacral dysplasia with type A lipodystrophy	LMNA	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic bone disease;Rare genetic skin disease;Rare genetic endocrine disease;Laminopathy
Orphanet:90154	Mandibuloacral dysplasia with type B lipodystrophy	ZMPSTE24	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic bone disease;Rare genetic skin disease;Rare genetic endocrine disease
Orphanet:90118	Severe early-onset axonal neuropathy due to MFN2 deficiency	MFN2	1	10 years) progressive distal muscle weakness and wasting of the lower limbs and later, to a lesser extent the upper limbs resulting in foot and wrist drop, areflexia, skeletal deformities (kyphoscoliosis, pes cavus with flattening, joint contractures), mild sensory impairment with vibration sense reduced to a greater extent than pain, optic atrophy and hearing loss. Wheelchair dependence by adolescence is usual and respiratory impairment with diaphragmatic paralysis may develop.	Rare genetic neurological disorder
Orphanet:90117	Hereditary motor and sensory neuropathy, Okinawa type	TFG	1	Hereditary motor and sensory neuropathy, Okinawa type is a rare, genetic, axonal hereditary motor and sensory neuropathy characterized by the adult-onset of slowly progressive, symmetric, proximal dominant muscle weakness and atrophy, painful muscle cramps, fasciculations and distal sensory impairment, mostly (but not exclusively) in individuals (and their descendents) from the Okinawa region in Japan. Absent deep tendon reflexes, elevated creatine kinase levels and autosomal dominant inheritance are also characteristic.	Rare genetic neurological disorder
Orphanet:90120	Hereditary motor and sensory neuropathy type 6	SLC25A46;MFN2	2	A rare axonal hereditary motor and sensoy neuropathy disease characterized by progressive, peripheral, axonal sensorimotor neuropathy (of variable severity), affecting predominantly the distal lower limbs, associated with progressive, variably severe, optic atrophy, which frequently leads to visual loss. Patients typically present distal limb muscle weakness and atrophy, hypo/areflexia, foot deformities, poor visual acuity (often with a central scotoma), nystagmus, and reduced peripheral and nocturnal vision. Additional reported manifestations include sensorineural hearing loss, major joint contractures, anosmia, scoliosis/lumbar hyperlordosis, cognitive impairment and vocal cord paresis.	Rare genetic neurological disorder
Orphanet:88644	Autosomal recessive ataxia, Beauce type	SYNE1	1	 gene mutations.	Rare genetic neurological disorder
Orphanet:88660	Hypertension due to gain-of-function mutations in the mineralocorticoid receptor	NR3C2	1	Hypertension due to gain-of-function mutations in the mineralocorticoid receptor is a rare genetic hypertension characterized by a familial severe hypertension with an onset before age 20 years, associated with suppressed plasma renin and low aldosterone levels in the presence of low or normal levels of the mineralocorticoid aldosterone, that is highly resistant to antihypertensive medication. During pregnancy, there is a marked exacerbation of hypertension, accompanied by low serum potassium levels and undetectable aldosterone levels, but without signs of preeclampsia, requiring early delivery.	Rare genetic renal disease
Orphanet:88637	Hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome	POLR3B;POLR1C;POLR3A	3	Hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome is characterised by the association of demyelinating leukodystrophy with progressive cerebellar ataxia, hypogonadotropic hypogonadism and hypodontia.	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility;Rare genetic neurological disorder
Orphanet:88639	Neurodegeneration due to 3-hydroxyisobutyryl-CoA hydrolase deficiency	HIBCH	1	 gene, encoding 3-hydroxyisobutyryl-CoA hydrolase. The mode of transmission has not yet been established.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:88642	Channelopathy-associated congenital insensitivity to pain	SCN9A;SCN10A;SCN11A	3	NA	Rare genetic neurological disorder
Orphanet:88632	Anterior segment developmental anomaly	FOXE3;PITX3	2	NA	NA
Orphanet:88635	Vacuolar myopathy with sarcoplasmic reticulum protein aggregates	CASQ1	1	Myopathy due to calsequestrin and SERCA1 protein overload is characterised by mild myopathy or elevated levels of creatine kinase in the blood without associated symptoms.	Rare genetic neurological disorder
Orphanet:88621	Ichthyosis-prematurity syndrome	SLC27A4	1	Ichthyosis prematurity syndrome is a rare, syndromic congenital ichthyosis characterized by premature birth (at gestational weeks 30-32, in general) in addition to thick, caseous and desquamating epidermis, neonatal respiratory asphyxia, and persistent eosinophilia. After the perinatal period, a spontaneous improvement in the health of affected patients is observed and skin features (vernix caseosa-like scale) evolve into a mild presentation of flat follicular hyperkeratosis with atopy.	Rare genetic skin disease
Orphanet:88628	Posterior column ataxia-retinitis pigmentosa syndrome	FLVCR1	1	Posterior column ataxia - retinitis pigmentosa is characterized by the association of progressive sensory ataxia and retinitis pigmentosa.	Rare genetic neurological disorder
Orphanet:88629	Tritanopia	OPN1SW	1	Tritanopia is an extremely rare form of colour blindness characterised by a selective deficiency of blue vision.	Rare genetic eye disease
Orphanet:88630	Terminal osseous dysplasia-pigmentary defects syndrome	FLNA	1	Terminal osseous dysplasia-pigmentary defects syndrome is characterised by malformation of the hands and feet, pigmentary skin lesions on the face and scalp and digital fibromatosis.	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:88620	Isolated congenital anosmia	TENM1;CNGA2	2	This syndrome is characterised by total or partial anosmia at birth. So far, 15 patients have been described. The anosmia is caused by a defect in the development of the olfactory bulbs or by replacement of the olfactory epithelium by respiratory epithelium. The mode of transmission appears to be autosomal dominant with incomplete penetrance. Isolated congenital anosmia is found in some parents of individuals with Kallman syndrome (see this term).	
Orphanet:88619	Familial acute necrotizing encephalopathy	RANBP2	1	Familial acute necrotizing encephalopathy or ADANE is a potentially fatal neurological disease characterised by neuropathological lesions principally involving the brainstem, thalamus and putamen.	
Orphanet:88618	Psychomotor delay due to S-adenosylhomocysteine hydrolase deficiency	AHCY	1	Psychomotor retardation due to S-adenosylhomocysteine hydrolase deficiency is characterised by psychomotor delay and severe myopathy (hypotonia, absent tendon reflexes and delayed myelination) from birth, associated with hypermethioninaemia and elevated serum creatine kinase levels.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:88616	Autosomal recessive non-syndromic intellectual disability	DCPS;B3GALNT2;AIMP1;CRBN;MED13L;TUSC3;TECR;GRIK2;WASHC4;TRAPPC9;PRSS12;MED23;ST3GAL3;CRADD;ZC3H14;NSUN2;LINS1;PGAP1;METTL23;CLIP1;FBXO31;NDST1;FMN2;EDC3;HNMT;EZR;LMAN2L;TNIK;PIGC;SLC45A1;FRRS1L;MBOAT7;C12ORF4;SARS;MED25;CC2D1A;MAN1B1;WARS2	38	NA	Rare genetic neurological disorder
Orphanet:87503	Mal de Meleda	SLURP1	1	Mal de Meleda (MdM) is a diffuse palmoplantar keratoderma, initially reported in the Island of Meleda, characterized by symmetric palmoplantar hyperkeratosis that progressively extends to the dorsal surfaces of hands and feet (transgrediens). The disease can be associated to hyperhidrosis, lichenoid plaques and perioral erythema.	Rare genetic skin disease
Orphanet:86923	Hereditary palmoplantar keratoderma, Gamborg-Nielsen type	SLURP1	1	Hereditary palmoplantar keratoderma, Gamborg-Nielsen type is characterised by the presence of diffuse palmoplantar keratoderma without associated symptoms. The syndrome has been described in multiple families from the northernmost county of Sweden (Norrbotten). The palmoplantar keratoderma found in the Gamborg-Nielsen type disease is milder than that found in Mal de Meleda but more severe than that found in Thost-Unna palmoplantar keratoderma (see these terms). Transmission is autosomal recessive.	Rare genetic skin disease
Orphanet:86920	Dermatopathia pigmentosa reticularis	KRT14	1	A rare, genetic, ectodermal dysplasia characterized by a widespread, early-onset, reticulate hyperpigmentation that persists throughout life, mild, diffuse non-cicatricial alopecia, and onychodystrophy. There are no dental anomalies. Patients may also present with adermatoglyphia, palmoplantar hyperkeratosis, acral dorsal blistering, and hypohidrosis or hyperhidrosis.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:522077	Infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome	SYT1	1	NA	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:521450	LAMA5-related multisystemic syndrome	LAMA5	1	NA	
Orphanet:521445	Microcephaly-facial dysmorphism-ocular anomalies-multiple congenital anomalies syndrome	ADAMTSL1	1	NA	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder
Orphanet:521438	Congenital vertebral-cardiac-renal anomalies syndrome	KYNU;HAAO	2	NA	Genetic otorhinolaryngologic disease;Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Rare genetic cardiac disease
Orphanet:521432	Congenital cataract-severe neonatal hepatopathy-global developmental delay syndrome	CYP51A1	1	NA	Rare genetic eye disease;Rare genetic hepatic disease
Orphanet:521426	PLAA-associated neurodevelopmental disorder	PLAA	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:521414	Autosomal dominant Charcot-Marie-Tooth disease type 2DD	ATP1A1	1	NA	Rare genetic neurological disorder
Orphanet:521258	Xq25 microduplication syndrome	STAG2	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare chromosomal anomaly
Orphanet:521305	Proximal myopathy with focal depletion of mitochondria	CHKB	1	NA	Rare genetic neurological disorder
Orphanet:521390	Spastic paraplegia-intellectual disability-nystagmus-obesity syndrome	KIDINS220	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease
Orphanet:89838	Epidermolysis bullosa simplex, autosomal recessive K14	KRT14	1	Epidermolysis bullosa simplex, autosomal recessive K14 (EBS-AR KRT14) is a basal subtype of epidermolysis bullosa simplex (EBS) characterized by generalized or, less frequently, localized acral blistering.	Rare genetic skin disease
Orphanet:521406	Dystonia-parkinsonism-hypermanganesemia syndrome	SLC39A14	1	NA	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:521411	Autosomal recessive axonal Charcot-Marie-Tooth disease due to copper metabolism defect	SCO2	1	NA	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:88949	MUC1-related autosomal dominant tubulointerstitial kidney disease	MUC1	1	NA	Rare genetic renal disease
Orphanet:88950	UMOD-related autosomal dominant tubulointerstitial kidney disease	UMOD	1	NA	Rare genetic renal disease
Orphanet:88940	Pseudohypoaldosteronism type 2C	WNK1	1	NA	Rare genetic renal disease
Orphanet:88939	Pseudohypoaldosteronism type 2B	WNK4	1	NA	Rare genetic renal disease
Orphanet:88924	Autosomal dominant polycystic kidney disease type 1 with tuberous sclerosis	TSC2;PKD1	2	Polycystic kidney disease with tuberous sclerosis (PKD-TSC) is characterised by early-onset and severe polycystic kidney disease with various manifestations of tuberous sclerosis (multiple angiomyolipomas, lymphangioleiomyomatosis and periventricular calcifications of the central nervous system).	Rare genetic renal disease;Rare chromosomal anomaly
Orphanet:88918	Autosomal dominant Alport syndrome	COL4A3;COL4A4	2	NA	Genetic otorhinolaryngologic disease;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic renal disease
Orphanet:88919	Autosomal recessive Alport syndrome	COL4A3;COL4A4	2	NA	Genetic otorhinolaryngologic disease;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic renal disease
Orphanet:88917	X-linked Alport syndrome	COL4A5	1	NA	Genetic otorhinolaryngologic disease;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic renal disease
Orphanet:93256	Fragile X-associated tremor/ataxia syndrome	FMR1	1	Fragile X-associated tremor/ataxia syndrome (FXTAS) is a rare neurodegenerative disorder characterized by adult-onset progressive intention tremor and gait ataxia.	Rare genetic neurological disorder
Orphanet:528105	Hypohidrosis-electrolyte imbalance-lacrimal gland dysfunction-ichthyosis-xerostomia syndrome	CLDN10	1	NA	Rare genetic renal disease
Orphanet:528091	Hydrops-lactic acidosis-sideroblastic anemia-multisystemic failure syndrome	LARS2	1	NA	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:93221	Sporadic idiopathic steroid-resistant nephrotic syndrome with minimal changes	NPHS2	1	NA	Rare genetic renal disease
Orphanet:93220	Sporadic idiopathic steroid-resistant nephrotic syndrome with diffuse mesangial sclerosis	PLCE1;WT1	2	NA	Rare genetic renal disease
Orphanet:93218	Sporadic idiopathic steroid-resistant nephrotic syndrome with focal segmental hyalinosis	CD2AP;NPHS2;APOL1	3	NA	Rare genetic renal disease
Orphanet:528084	Non-specific syndromic intellectual disability	RLIM;ACTL6A	2	NA	Rare genetic neurological disorder
Orphanet:93217	Familial idiopathic steroid-resistant nephrotic syndrome with diffuse mesangial sclerosis	NUP93;PLCE1;PTPRO;WT1;NPHS1;ARHGDIA	6	NA	Rare genetic renal disease
Orphanet:93216	Familial idiopathic steroid-resistant nephrotic syndrome with minimal changes	PTPRO;NPHS1;NPHS2;EMP2	4	NA	Rare genetic renal disease
Orphanet:93214	Familial idiopathic steroid-resistant nephrotic syndrome with diffuse mesangial proliferation	PTPRO;NPHS1;ANKFY1	3	NA	Rare genetic renal disease
Orphanet:93262	Crouzon syndrome-acanthosis nigricans syndrome	FGFR3	1	Crouzon syndrome with acanthosis nigricans (CAN) is a very rare, clinically heterogeneous form of faciocraniostenosis with Crouzon-like features and premature synostosis of cranial sutures (Crouzon disease, see this term), associated with acanthosis nigricans (AN; see this term).	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease
Orphanet:93260	Pfeiffer syndrome type 3	FGFR2	1	Pfeiffer syndrome type 3 (PS3) is a severe type of Pfeiffer syndrome (PS; see this term), characterized by bicoronal craniosynostosis, severe associated functional disorders, and hand, foot and elbow abnormalities.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93259	Pfeiffer syndrome type 2	FGFR2	1	Pfeiffer syndrome type 2 (PS2) is a frequent and severe type of Pfeiffer syndrome (PS; see this term), characterized by cloverleaf skull, severe associated functional disorders, and hand/foot and elbow/knee abnormalities.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93258	Pfeiffer syndrome type 1	FGFR1;FGFR2	2	Pfeiffer syndrome type 1 (PS1) is a mild to moderately severe type of Pfeiffer syndrome (PS; see this term), characterized by bicoronal craniosynostosis, variable finger and toe malformations, and in most cases, normal intellectual development.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93271	Short rib-polydactyly syndrome, Verma-Naumoff type	IFT80;DYNC2H1;WDR35;WDR60;WDR34	5	Short rib-polydactyly syndrome, Verma-Naumoff type is a short rib-polydactyly syndrome characterized by short limb dwarfism, short ribs with thoracic dysplasia, postaxial polydactyly and protuberant abdomen. Associated multiple malformations include cardiovascular defects, renal agenesis /hypoplasia, abnormal cloacal development (ambiguous genitalia, anal atresia) and cerebellar hypoplasia. Short rib-polydactyly syndrome, Verma-Naumoff type follows an autosomal recessive mode of transmission. The disease is usually fatal in the perinatal period.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93269	Short rib-polydactyly syndrome, Majewski type	TRAF3IP1;DYNC2H1;NEK1	3	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93270	Short rib-polydactyly syndrome, Saldino-Noonan type	DYNC2H1	1	Short rib-polydactyly syndrome (SRPS), Saldino-Noonan type is an extremely rare type of SRPS with neonatal onset characterized by polydactyly, hydropic appearance, and small thorax with short horizontal ribs causing fatal cardiorespiratory distress. Affected patients also have extreme micromelia, pointed metaphyses, and a range of other ossification defects (vertebrae, calvaria, pelvis, hand and foot bones). Extraskeletal manifestations may include polycystic kidneys, transposition of the great vessels, and atresia of the gastrointestinal and genitourinary systems.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93268	Short rib-polydactyly syndrome, Beemer-Langer type	IFT122	1	Short rib-polydactyly syndrome (SRPS), Beemer-Langer type is an extremely rare type of SRPS developing prenatally or immediately after birth and characterized by short and narrow thorax with horizontally oriented ribs. Other bone features include small iliac bones, short tubular bones, bowing of long bones and rarely pre- and post-axial polydactyly. Brain defects are common and some cases of cleft lip, absent internal genitalia and renal, biliary and pancreatic cysts have been reported. The course is rapidly fatal.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93282	Spondyloepimetaphyseal dysplasia, PAPSS2 type	PAPSS2	1	Spondyloepimetaphyseal dysplasia (SEMD), Pakistani type is characterized by short stature, short and bowed lower limbs, mild brachydactyly, kyphoscoliosis, abnormal gait, enlarged knee joints, precocious osteoarthropathy, and normal intelligence.	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:93283	Spondyloepiphyseal dysplasia, Kimberley type	ACAN	1	Spondyloepiphyseal dysplasia, Kimberley type (SEDK) is characterized by short stature and premature degenerative arthropathy.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93279	Mild spondyloepiphyseal dysplasia due to COL2A1 mutation with early-onset osteoarthritis	COL2A1	1	Mild spondyloepiphyseal dysplasia due to COL2A1 mutation with early-onset osteoarthritis is a type 2 collagen-related bone disorder characterized by precocious, generalized osteoarthritis (with onset as early as childhood) and mild, dysplastic spinal changes (flattening of vertebrae, irregular endplates and wedge-shaped deformities) resulting in a mildly short trunk.	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:93276	Polyostotic fibrous dysplasia	GNAS	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93277	Monostotic fibrous dysplasia	GNAS	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93274	Thanatophoric dysplasia type 2	FGFR3	1	).	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:527497	NKX6-2-related autosomal recessive hypomyelinating leukodystrophy	NKX6-2	1	NA	Rare genetic neurological disorder
Orphanet:527450	Severe myopia-generalized joint laxity-short stature syndrome	GZF1	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93100	Renal agenesis, unilateral	RET;FRAS1;BMP4;FREM2;FREM1;UPK3A;DSTYK;GREB1L	8	Unilateral renal agenesis (URA) is a form of renal agenesis (see this term) characterized by the complete absence of development of one kidney accompanied by an absent ureter.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis
Orphanet:527468	Diaphragmatic hernia-short bowel-asplenia syndrome	HLX	1	NA	Rare genetic developmental defect during embryogenesis
Orphanet:92050	Congenital tufting enteropathy	EPCAM	1	Congenital Tufting Enteropathy is a rare congenital enteropathy presenting with early-onset severe and intractable diarrhea that leads to irreversible intestinal failure.	Rare genetic gastroenterological disease
Orphanet:93160	Hypocalcemic vitamin D-resistant rickets	VDR	1	Hypocalcemic vitamin D-resistant rickets (HVDRR) is a hereditary disorder of vitamin D action characterized by hypocalcemia, severe rickets and in many cases alopecia.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic endocrine disease
Orphanet:93114	Autosomal dominant intermediate Charcot-Marie-Tooth disease type E	INF2	1	A rare hereditary motor and sensory neuropathy disorder characterized by the typical CMT phenotype (slowly progressive distal muscle weakness and atrophy in upper and lower limbs, distal sensory loss in extremities, reduced or absent deep tendon reflexes and foot deformities) associated with focal segmental glomerulosclerosis (manifesting with proteinuria and progression to end-stage renal disease). Mild or moderate sensorineural hearing loss may also be associated. Nerve biopsy reveals both axonal and demyelinating changes and nerve conduction velocities vary from the demyelinating to axonal range (typically between 25-50m/sec).	Rare genetic renal disease;Rare genetic neurological disorder
Orphanet:93111	HNF1B-related autosomal dominant tubulointerstitial kidney disease	HNF4A;HNF1B	2	Renal cysts and diabetes syndrome (RCAD) is a rare form of maturity-onset diabetes of the young (MODY; see this term) characterized clinically by heterogeneous cystic renal disease and early-onset familial non-autoimmune diabetes. Pancreatic atrophy, liver dysfunction and genital tract anomalies are also features of the syndrome.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease
Orphanet:93207	Idiopathic steroid-sensitive nephrotic syndrome with minimal change	EMP2	1	NA	Rare genetic renal disease
Orphanet:93209	Idiopathic steroid-sensitive nephrotic syndrome with diffuse mesangial proliferation	EMP2	1	NA	Rare genetic renal disease
Orphanet:93213	Familial idiopathic steroid-resistant nephrotic syndrome with focal segmental hyalinosis	NUP205;INF2;CD2AP;NUP93;ACTN4;NPHS1;GAPVD1;TRPC6;WT1;COL4A3;PAX2;MYO1E;PTPRO;ARHGAP24;COQ8B;ANLN;CRB2;NUP107;NPHS2;PLCE1	20	NA	Rare genetic renal disease
Orphanet:93206	Idiopathic steroid-sensitive nephrotic syndrome with focal segmental hyalinosis	EMP2	1	NA	Rare genetic renal disease
Orphanet:93322	Tibial hemimelia	GLI3	1	Tibial hemimelia is a rare congenital anomaly characterized by deficiency of the tibia with a relatively intact fibula.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93321	Radial hemimelia	LMBR1;SHH	2	Radial hemimelia is a congenital longitudinal deficiency of the radius bone of the forearm characterized by partial or total absence of the radius.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93325	Autosomal dominant Kenny-Caffey syndrome	FAM111A	1	A rare, primary bone dysplasia characterized by severe growth retardation, short stature, cortical thickening and medullary stenosis of long bones, delayed closure of the anterior fontanelle, absent diploic space in the skull bones, prominent forehead, macrocephaly, dental anomalies, eye problems (hypermetropia and pseudopapilledema), and hypocalcemia due to hypoparathyroidism, sometimes resulting in convulsions. Intelligence is normal.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic endocrine disease
Orphanet:93324	Autosomal recessive Kenny-Caffey syndrome	TBCE	1	A rare, primary bone dysplasia characterized by prenatal and postnatal growth retardation, short stature, cortical thickening and medullary stenosis of the long bones, absent diploic space in the skull bones, hypocalcemia due to the hypoparathyroidism, small hands and feet, delayed mental and motor development, intellectual disability, dental anomalies, and dysmorphic features, including prominent forehead, small deep-set eyes, beaked nose, and micrognathia.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic endocrine disease
Orphanet:93329	Autosomal recessive omodysplasia	GPC6	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93328	Autosomal dominant omodysplasia	FZD2	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93336	Polydactyly of a triphalangeal thumb	SHH;LMBR1	2	Polydactyly of a triphalangeal thumb or PPD2 is a form of preaxial polydactyly of fingers (see this term), a limb malformation syndrome, that is characterized by the presence of a usually opposable triphalangeal thumb with or without additional duplication of one or more skeletal components of the thumb. The thumb appearance can differ widely in shape (wedge to rectangular) or it can be deviated in the radio-ulnar plane (clinodactyly). PPD2 is also associated with systemic syndromes, including Holt-Oram syndrome and Fanconi anemia (see these terms).	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93335	Postaxial polydactyly type B	GLI3	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93334	Postaxial polydactyly type A	ZNF141;IQCE;GLI3	3	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93333	Pelviscapular dysplasia	TBX15	1	Pelviscapular dysplasia (Cousin syndrome) is characterized by the association of pelviscapular dysplasia with epiphyseal abnormalities, congenital dwarfism and facial dysmorphism.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93338	Polysyndactyly	GLI3	1	Polysyndactyly or PPD4 is a form of preaxial polydactyly of fingers (see this term), a limb malformation syndrome, characterized by the presence of a thumb showing the mildest degree of duplication, being broad, bifid or with radially deviated distal phalanx. Syndactyly of various degrees of third-and-fourth fingers is occasionally present.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93349	X-linked spondyloepimetaphyseal dysplasia	BGN	1	A rare, genetic primary bone dysplasia disorder characterized by disproportionate short stature with mesomelic short limbs, leg bowing, lumbar lordosis, brachydactyly, joint laxity and a waddling gait. Radiographs show platyspondyly with central protrusion of anterior vertebral bodies, kyphotic angulation and very short long bones with dysplastic epiphyses and flarred, irregular, cupped metaphyses.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93346	Spondyloepimetaphyseal dysplasia congenita, Strudwick type	COL2A1	1	Spondyloepimetaphyseal dysplasia congenita, Strudwick type is characterized by disproportionate short stature from birth (with a very short trunk and shortened limbs) and skeletal abnormalities (lordosis, scoliosis, flattened vertebrae, pectus carinatum, coxa vara, clubfoot, and abnormal epiphyses or metaphyses).	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:93347	Anauxetic dysplasia	RMRP;POP1	2	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93356	Spondyloepimetaphyseal dysplasia, Missouri type	MMP13	1	Spondyloepimetaphyseal dysplasia, Missouri type is characterized by moderate-to-severe metaphyseal changes, mild epiphyseal involvement, rhizomelic shortening of the lower limbs with bowing of the femora and/or tibiae, coxa vara, genu varum and pear-shaped vertebrae in childhood.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93352	Spondyloepimetaphyseal dysplasia, Shohat type	DDRGK1	1	Spondyloepimetaphyseal dysplasia congenita, Shohat type is characterized by severely disproportionate short stature, short limbs, small chest, short neck, thin lips, severe lumbar lordosis, marked genu varum, joint laxity, distended abdomen, mild hepatomegaly and splenomegaly.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93284	Spondyloepiphyseal dysplasia tarda	TRAPPC2	1	Spondyloepiphyseal dysplasia tarda (SEDT) is characterized by disproportionate short stature in adolescence or adulthood, associated with a short trunk and arms and barrel-shaped chest.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93296	Achondrogenesis type 2	COL2A1	1	A rare, lethal type of achondrogenesis, and part of the spectrum of type 2 collagen-related bone disorders, characterized by severe micromelia, short neck with large head, small thorax, protuberant abdomen, underdeveloped lungs, distinctive facial features such as a prominent forehead, a small chin, a cleft palate (in some) and distinctive histological features of the cartilage.	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:93298	Achondrogenesis type 1B	SLC26A2	1	A rare, lethal type of achondrogenesis characterized by severe micromelia with very short fingers and toes, a flat face, a short neck, thickened soft tissue around the neck, hypoplasia of the thorax, protuberant abdomen, a hydropic fetal appearance and distinctive histological features of the cartilage.	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:93297	Hypochondrogenesis	COL2A1	1	NA	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:93299	Achondrogenesis type 1A	TRIP11	1	A rare, lethal type of achondrogenesis characterized by dwarfism with extremely short limbs, narrow chest, short ribs that are easily fractured, soft skull bones and distinctive histological features of the cartilage.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93304	Autosomal dominant brachyolmia	TRPV4	1	A relatively severe form of brachyolmia, a group of rare genetic skeletal disorders, characterized by short-trunked short stature, platyspondyly and kyphoscoliosis. Degenerative joint disease (osteoarthropathy) in the spine, large joints and interphalangeal joints becomes manifest in adulthood.	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:93307	Multiple epiphyseal dysplasia type 4	SLC26A2	1	Multiple epiphyseal dysplasia type 4 is a multiple epiphyseal dysplasia with a late-childhood onset, characterized by joint pain involving hips, knees, wrists, and fingers with occasional limitation of joint movements, deformity of hands, feet, and knees (club foot, clinodactyly, brachydactyly), scoliosis and slightly reduced adult height. Radiographs display flat epiphyses with early arthritis of the hip, and double-layered patella. Multiple epiphyseal dysplasia type 4 follows an autosomal recessive mode of transmission. The disease is allelic to diastrophic dwarfism, atelosteogenesis type 2 and achondrogenesis type 1B with whom it forms a clinical continuum.	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:93308	Multiple epiphyseal dysplasia type 1	COMP	1	Multiple epiphyseal dysplasia type 1 (MED 1) is a form of multiple epiphyseal dysplasia that is characterized by normal or mild short stature, pain in the hips and/or knees, progressive deformity of extremities and early-onset osteoarthrosis. Specific features to MED 1 include a more pronounced involvement of hip joints and gait abnormality and a shorter adult height. MED1 is allelic to pseudoachondroplasia with which it shares clinical and radiological features. The disease follows an autosomal dominant mode of transmission.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93311	Multiple epiphyseal dysplasia type 5	MATN3	1	Multiple epiphyseal dysplasia type 5 is a multiple epiphyseal dysplasia characterized by an early-onset of pain and stiffness (involving knee and hip), progressive deformity of the extremities and precocious osteoarthritis associated with delayed and irregular ossification of epiphyses. Features specific to multiple epiphyseal dysplasia, type 5 include normal stature and lesser incidence of gait abnormalities. Radiographs reveal epiphyseal and metaphyseal irregularities. Multiple epiphyseal dysplasia type 5 follows an autosomal dominant mode of transmission.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93314	Spondylometaphyseal dysplasia, Kozlowski type	TRPV4	1	Spondylometaphyseal dysplasia, Kozlowski type is characterized by short stature (short-trunk dwarfism), scoliosis, metaphyseal abnormalities in the femur (prominent in the femoral neck and trochanteric area), coxa vara and generalized platyspondyly.	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:93315	Spondylometaphyseal dysplasia, 'corner fracture' type	COL2A1;FN1	2	Spondylometaphyseal dysplasia, 'corner fracture' type is a skeletal dysplasia associated with short stature, developmental coxa vara, progressive hip deformity, simulated 'corner fractures' of long tubular bones and vertebral body abnormalities (mostly oval vertebral bodies).	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:93316	Spondylometaphyseal dysplasia, Schmidt type	COL2A1	1	Spondylometaphyseal dysplasia, Schmidt type is characterized by short stature, myopia, ,small pelvis, progressive kypho-scoliosis, wrist deformity, severe genu valgum, short long bones, and severe metaphyseal dysplasia with moderate spinal changes and minimal changes in the hands and feet.	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:93317	Spondylometaphyseal dysplasia, Sedaghatian type	GPX4	1	Spondylometaphyseal dysplasia (SEMD), Sedaghatian type is a neonatal lethal form of spondylometaphyseal dysplasia characterized by severe metaphyseal chondrodysplasia, mild rhizomelic shortness of the upper limbs, and mild platyspondyly.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:90673	Hypothyroidism due to TSH receptor mutations	TSHR	1	A type of primary congenital hypothyroidism, a permanent thyroid hormone deficiency that is present from birth due to thyroid resistance to TSH.	Rare genetic endocrine disease
Orphanet:90674	Isolated thyroid-stimulating hormone deficiency	TSHB	1	A type of central congenital hypothyroidism, a permanent thyroid deficiency that is present from birth, characterized by low levels of thyroid hormones due to a deficiency in TSH synthesis.	Rare genetic endocrine disease
Orphanet:90658	Charcot-Marie-Tooth disease type 1E	PMP22	1	 mutation, with some cases being very mild and even resembling hereditary neuropathy with liability to pressure palsies, while others having an earlier onset with a more severe phenotype (reminiscent of Dejerine-Sottas syndrome) than that seen in CMT1A, caused by gene duplication. These severe cases may also report deafness and much slower motor nerve conduction velocities compared to CMT1A patients.	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder
Orphanet:90791	Congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency	HSD3B2	1	A very rare form of congenital adrenal hyperplasia (CAH) encompassing salt-wasting and non-salt wasting forms with a wide variety of symptoms, including glucocorticoid deficiency and male undervirilization manifesting as a micropenis to severe perineoscrotal hypospadias.	Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease;Rare genetic gynecological and obstetrical diseases
Orphanet:90695	Panhypopituitarism	SOX3;PROP1	2	NA	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility
Orphanet:90625	X-linked non-syndromic sensorineural deafness type DFN	PRPS1;COL4A6;SMPX	3	NA	
Orphanet:90635	Autosomal dominant non-syndromic sensorineural deafness type DFNA	KITLG;SSBP1;PDE1C;SLC44A4;POU4F3;SIX1;TECTA;TMC1;WFS1;COCH;COL11A2;GSDME;EYA4;GJB2;GJB3;GJB6;KCNQ4;MYH14;MYH9;MYO6;MYO7A;CCDC50;GRHL2;CRYM;ACTG1;SLC17A8;MIR96;TBC1D24;TJP2;CEACAM16;DIAPH3;DIABLO;P2RX2;TNC;MYO1C;OSBPL2;HOMER2;MCM2;CD164;PTPRQ;DMXL2;MYO1A	42	NA	
Orphanet:90636	Autosomal recessive non-syndromic sensorineural deafness type DFNB	BDP1;ROR1;WBP2;EPS8L2;SLC26A4;BSND;CDH23;TECTA;TMC1;TMIE;TMPRSS3;USH1C;COL11A2;ELMOD3;GJB2;GJB3;GJB6;MET;MYO15A;MYO6;MYO7A;OTOF;PCDH15;WHRN;STRC;TRIOBP;RDX;LHFPL5;ESPN;ESRRB;MARVELD2;MYO3A;SLC26A5;OTOA;PJVK;CLDN14;LRTOMT;HGF;LOXHD1;GRXCR1;TPRN;PTPRQ;SERPINB6;TBC1D24;GPSM2;MSRB3;ILDR1;KARS;GIPC3;TSPEAR;CIB2;CABP2;OTOG;PNPT1;OTOGL;SYNE4;SLITRK6;GRXCR2;EPS8;ADCY1;CLIC5;RIPOR2;DCDC2;ATP2B2;S1PR2;MPZL2;CDC14A;GJA1	68	NA	
Orphanet:90368	Hypotrichosis simplex of the scalp	KRT74;CDSN	2	Hypotrichosis simplex of the scalp (HSS) is characterized by diffuse progressive hair loss that is confined to the scalp.	Rare genetic skin disease
Orphanet:90389	Telangiectasia macularis eruptiva perstans	KIT	1	NA	
Orphanet:90653	Stickler syndrome type 1	COL2A1	1	NA	Genetic otorhinolaryngologic disease;Rare genetic bone disease;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:90652	Otopalatodigital syndrome type 2	FLNA	1	A severe form of otopalatodigital syndrome spectrum disorder, and is characterized by dysmorphic facies, severe skeletal dysplasia affecting the axial and appendicular skeleton, extraskeletal anomalies (including malformations of the brain, heart, genitourinary system, and intestine) and poor survival.	Genetic otorhinolaryngologic disease;Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare genetic bone disease
Orphanet:90654	Stickler syndrome type 2	COL11A1	1	NA	Genetic otorhinolaryngologic disease;Rare genetic bone disease;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:90647	Jervell and Lange-Nielsen syndrome	KCNE1;KCNQ1	2	Jervell and Lange-Nielsen syndrome (JLNS) is an autosomal recessive variant of familial long QT syndrome (see this term) characterized by congenital profound bilateral sensorineural hearing loss, a long QT interval on electrocardiogram and ventricular tachyarrhythmias.	Genetic otorhinolaryngologic disease;Rare genetic cardiac disease
Orphanet:90650	Otopalatodigital syndrome type 1	FLNA	1	A disorder that is the mildest form of otopalatodigital syndrome spectrum disorder, and is characterized by a generalized skeletal dysplasia, mild intellectual disability, conductive hearing loss, and typical facial anomalies.	Genetic otorhinolaryngologic disease;Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare genetic bone disease
Orphanet:90641	Mitochondrial non-syndromic sensorineural deafness	TFB1M;TRMU;MT-CO1;MT-RNR1;MT-TH;MT-TS1	6	NA	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection	FOXE3;LOX;MAT2A;ELN;TGFB3;TGFBR1;TGFBR2;FBN1;MYH11;ACTA2;MYLK;SMAD3;PRKG1;MFAP5;TGFB2	15	Familial thoracic aortic aneurysm and aortic dissection is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch or descending aorta) in the absence of any other associated disease. Depending on the size, location and progression rate of dilatation/dissection, patients may be asymptomatic or may present dyspnea, cough, jaw, neck, chest or back pain, head, neck or upper limb edema, difficulty swallowing, voice hoarseness, pale skin, faint pulse and/or numbness/tingling in limbs. Patients have increased risk of presenting life threatening aortic rupture.	Rare genetic systemic or rheumatologic disease;Rare genetic vascular disease
Orphanet:91411	Congenital ptosis	COL25A1;ZFHX4	2	Congenital ptosis is characterized by superior eyelid drop present at birth.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:91496	Snowflake vitreoretinal degeneration	KCNJ13	1	Snowflake vitreoretinal degeneration (SVD) is characterised by the presence of small granular-like deposits resembling snowflakes in the retina, fibrillary vitreous degeneration and cataract. The prevalence is unknown but the disorder has been described in several families. Transmission is autosomal dominant and the causative gene has been localised to a small region on chromosome 2q36.	Rare genetic eye disease
Orphanet:91495	Persistent hyperplastic primary vitreous	FZD4;NDP;ATOH7	3	NA	Rare genetic eye disease
Orphanet:91481	Ring dermoid of cornea	PITX2	1	 gene have been suggested as a potential cause of the condition.	Rare genetic eye disease;Rare genetic tumor
Orphanet:91414	Pilomatrixoma	CTNNB1	1	Pilomatrixoma is a rare and benign hair cell-derived tumor occurring mostly in young adults (usually under the age of 20) and characterized as a 3-30 mm solitary, painless, firm, mobile, deep dermal or subcutaneous tumor, most commonly found in the head, neck or upper extremities. When superficial, the tumors tint the skin blue-red. Multiple pilomatrixomas are seen in myotonic dystrophy, Gardner syndrome, Rubinstein-Taybi syndrome, and Turner syndrome (see these terms).	
Orphanet:91490	Isolated congenital sclerocornea	GJA8	1	NA	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:91489	Isolated congenital megalocornea	CHRDL1	1	12.5 mm) and a deep anterior eye chamber, without an elevation in intraocular pressure. It can manifest with mild to moderate myopia as well as photophobia and iridodonesis (due to iris hypoplasia). Associated complications include lens dislocation, retinal detachment, presenile cataract development, and secondary glaucoma.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:91483	Rieger anomaly	PITX2;FOXC1	2	Rieger's anomaly is a congenital ocular defect caused by anterior segment dysgenesis and is characterized by severe anterior chamber deformity with prominent strands and marked atrophy of the iris stroma, with hole or pseudo-hole formation and corectopia. The term covers the association of these iris and pupil anomalies with the features of Axenfeld’s anomaly (see this term).	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:91130	Cardiomyopathy-hypotonia-lactic acidosis syndrome	SLC25A3	1	 gene encoding a mitochondrial membrane transporter.	Rare genetic cardiac disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:91131	DK1-CDG	DOLK	1	 gene led to a 96 to 98% reduction in DK activity.	Rare inborn errors of metabolism;Rare genetic skin disease;Rare genetic cardiac disease
Orphanet:91132	Ichthyosis-hypotrichosis syndrome	ST14	1	 gene, encoding the recently identified protease, matriptase. Analysis of skin samples from the patients suggests that this enzyme plays a role in epidermal desquamation.	Rare genetic skin disease
Orphanet:90793	Congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency	CYP17A1	1	A very rare form of congenital adrenal hyperplasia (CAH) characterized by glucocorticoid deficiency, hypergonadotrophic hypogonadism and severe hypokalemic hypertension.	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease
Orphanet:90795	Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency	CYP11B1	1	A rare form of congenital adrenal hyperplasia (CAH) characterized by glucocorticoid deficiency, hyperandrogenism, hypertension and virilization in females.	Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease;Rare genetic gynecological and obstetrical diseases
Orphanet:90796	46,XY disorder of sex development due to isolated 17,20-lyase deficiency	CYB5A;CYP17A1	2	46,XY disorder of sex development due to isolated 17,20-lyase deficiency is a rare disorder of sex development due to reduced 17,20-lyase activity that affects individuals with 46,XY karyotype and is characterized by ambiguous external genitalia, including micropenis, perineal hypospadias, bifid scrotum, cryptorchidism, and a blind vaginal pouch. Blood pressure and electrolytes are normal whilst hormonal investigations show normal basal and stimulated levels of cortisol, and low basal and stimulated androgen levels.	Rare genetic gynecological and obstetrical diseases;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease
Orphanet:90797	Partial androgen insensitivity syndrome	AR	1	A disorder of sex development (DSD) distinct from complete AIS (CAIS) characterized by the presence of abnormal genital development in a 46,XY individual with normal testis development and partial responsiveness to age-appropriate levels of androgens.	Rare genetic gynecological and obstetrical diseases;Genetic infertility;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease
Orphanet:91347	TSH-secreting pituitary adenoma	CDH23	1	A rare, functioning, pituitary adenoma characterized by the presence of a pituitary mass associated with high levels of circulating, free, thyroid hormones in conjunction with normal to high levels of TSH and unresponsiveness of TSH levels to TRH stimulation and T3 suppression tests, typically manifesting with signs and symtoms of mild to moderate hyperthyroidism (e.g. goiter (most frequently observed), palpitation, excessive sweating, arrhythmia, weight loss, tremor) and/or tumor mass effect (such as headache, visual field defects, hypopituitarism). Occasionally, cosecretion of prolactin and/or growth hormone may cause galactorrhea and/or acromegaly.	Rare genetic endocrine disease
Orphanet:91352	Germinoma of the central nervous system	JMJD1C	1	NA	Rare genetic endocrine disease
Orphanet:91135	Body skin hyperlaxity due to vitamin K-dependent coagulation factor deficiency	GGCX	1	Body skin hyperlaxity due to vitamin K-dependent coagulation factor deficiency is a very rare genetic skin disease characterized by severe skin laxity affecting the trunk and limbs.	Rare genetic skin disease
Orphanet:79396	Epidermolysis bullosa simplex, generalized severe	KRT14;KRT5	2	Epidermolysis bullosa simplex, Dowling-Meara type (EBS-DM) is a basal subtype of epidermolysis bullosa simplex (EBS, see this term) characterized by the presence of generalized vesicles and small blisters in grouped or arcuate configuration.	Rare genetic skin disease
Orphanet:79397	Epidermolysis bullosa simplex with mottled pigmentation	KRT14;KRT5	2	Epidermolysis bullosa simplex with mottled pigmentation (EBS-MP) is a basal subtype of epidermolysis bullosa simplex (EBS, see this term) characterized by generalized blistering with mottled or reticulate brown pigmentation.	Rare genetic skin disease
Orphanet:79394	Congenital non-bullous ichthyosiform erythroderma	ABCA12;ALOX12B;ALOXE3;TGM1;NIPAL4;PNPLA1;CERS3	7	Congenital ichthyosiform erythroderma (CIE) is a variant of autosomal recessive congenital ichthyosis (ARCI; see this term), a rare epidermal disease, characterized by fine, whitish scales on a background of erythematous skin over the whole body.	Rare genetic skin disease;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:79395	Keratoderma hereditarium mutilans with ichthyosis	LOR	1	Keratoderma hereditarium mutilans with ichthyosis is a diffuse palmoplantar keratoderma characterized by honeycomb palmoplantar hyperkeratosis associated with pseudoainhum of the fifth digit of the hand, ichthyosis and deafness. Keratoderma hereditarium mutilans with ichthyosis follows an autosomal dominant mode of transmission.	Rare genetic skin disease
Orphanet:79414	Woolly hair nevus	HRAS	1	Woolly hair nevus (WHN) is a rare non-familial hair anomaly characterized by kinky, tightly coiled, and hypopigmented fine hair with an average diameter of 0.5 cm, noted, since birth or during the first two years of life, in a localized circumscribed distribution on the scalp. Occassionally, WHN grows in areas observed to be alopecic in the neonatal period. WHN can be associated with features like ocular defects (persistent pupillary membrane, retinal defects), precocious puberty, and epidermal nevi.	Rare genetic skin disease
Orphanet:79399	Epidermolysis bullosa simplex, generalized intermediate	KRT14;KRT5	2	Non-Dowling-Meara generalized epidermolysis bullosa simplex, formerly known as epidermolysis bullosa simplex, Köbner type (EBS-K) is a generalized basal subtype of epidermolysis bullosa simplex (EBS, see this term) characterized by non-herpetiform blisters and erosions arising in particular at sites of friction.	Rare genetic skin disease
Orphanet:79401	Epidermolysis bullosa simplex, Ogna type	PLEC	1	Epidermolysis bullosa simplex, Ogna type (EBS-O) is a basal subtype of epidermolysis bullosa simplex (EBS, see this term) characterized by sometimes widespread, primarily acral blistering.	Rare genetic skin disease
Orphanet:79400	Localized epidermolysis bullosa simplex	KRT14;KRT5	2	Localized epidermolysis bullosa simplex, formerly known as EBS, Weber-Cockayne, is a basal subtype of epidermolysis bullosa simplex (EBS, see this term). The disease is characterized by blisters occurring mainly on the palms and soles, exacerbated by warm weather.	Rare genetic skin disease
Orphanet:79403	Junctional epidermolysis bullosa-pyloric atresia syndrome	ITGA6;ITGB4	2	Junctional epidermolysis bullosa with pyloric atresia is a severe subtype of junctional epidermolysis bullosa (JEB, see this term) characterized by generalized blistering at birth and congenital atresia of the pylorus and rarely of other portions of the gastrointestinal tract.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:79402	Junctional epidermolysis bullosa, generalized intermediate	COL17A1;ITGB4;LAMA3;LAMB3;LAMC2	5	Generalized non-Herlitz-type junctional epidermolysis bullosa is a form of non-Herlitz-type junctional epidermolysis bullosa (JEB-nH, see this term) characterized by generalized skin blistering, atrophic scarring, nail dystrophy or nail absence, and enamel hypoplasia, with extracutaneous involvement.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:79405	Junctional epidermolysis bullosa inversa	LAMC2	1	Junctional epidermolysis bullosa inversa is a rare severe subtype of junctional epidermolysis bullosa (JEB, see this term) characterized by blistering and erosions confined to intertriginous skin sites, the esophagus, and vagina.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:79404	Junctional epidermolysis bullosa, generalized severe	LAMB3;LAMC2;LAMA3	3	Junctional epidermolysis bullosa, Herlitz-type is a severe subtype of junctional epidermolysis bullosa (JEB, see this term) characterized by blisters and extensive erosions, localized to the skin and mucous membranes.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:79406	Late-onset junctional epidermolysis bullosa	COL17A1	1	Late-onset junctional epidermolysis bullosa is a subtype of junctional epidermolysis bullosa (JEB, see this term) occurring in childhood or young adulthood.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:79409	Recessive dystrophic epidermolysis bullosa inversa	COL7A1	1	Recessive dystrophic epidermolysis bullosa inversa (RDEB-I) is rare subtype of dystrophic epidermolysis bullosa (DEB, see this term) characterized by blisters and erosions which are primarily confined to intertriginous skin sites, the base of the neck, the uppermost back, and the lumbosacral area.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:79408	Severe generalized recessive dystrophic epidermolysis bullosa	COL7A1;MMP1	2	Severe generalized recessive dystrophic epidermolysis bullosa (RDEB-sev gen) is the most severe subtype of dystrophic epidermolysis bullosa (DEB, see this term), formerly known as the Hallopeau-Siemens type, and is characterized by generalized cutaneous and mucosal blistering and scarring associated with severe deformities and major extracutaneous involvement.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:79411	Transient bullous dermolysis of the newborn	COL7A1	1	Transient bullous dermolysis of the newborn is a rare subtype of dystrophic epidermolysis bullosa (DEB, see this term) characterized by generalized blistering at birth that usually regresses within the first 6 to 24 months of life.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:79410	Pretibial dystrophic epidermolysis bullosa	COL7A1	1	Pretibial dystrophic epidermolysis bullosa is a rare subtype of dystrophic epidermolysis bullosa (DEB, see this term) characterized by the development of blisters, erosions, and lichenoid lesions predominantly in the pretibial region.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:79452	Milroy disease	VEGFC;FLT4;GJC2	3	Milroy disease is a frequent form of primary lymphedema (see this term) characterized generally by painless, chronic lower-limb lymphedema found at birth or developing in the early neonatal period.	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:79455	Cutaneous mastocytoma	KIT	1	Cutaneous mastocytoma is a form of cutaneous mastocytosis (CM, see this term) generally characterized by the presence of a solitary or multiple hyperpigmented macules, plaques or nodules associated with abnormal accumulation of mast cells in the skin.	
Orphanet:79435	Oculocutaneous albinism type 4	SLC45A2	1	Oculocutaneous albinism type 4 (OCA4) is a type of OCA (see this term) characterized by varying degrees of skin and hair hypopigmentation, numerous ocular changes and misrouting of the optic nerves at the chiasm.	Rare genetic eye disease;Rare inborn errors of metabolism;Rare genetic skin disease
Orphanet:79434	Oculocutaneous albinism type 1B	TYR	1	Oculocutaneous albinism type 1B (OCA1B) is a type of OCA1 (see this term) characterized by skin and hair hypopigmentation, nystagmus, reduced iris and retinal pigment and misrouting of the optic nerves.	Rare genetic eye disease;Rare inborn errors of metabolism;Rare genetic skin disease
Orphanet:79433	Oculocutaneous albinism type 3	TYRP1	1	Type 3 oculocutaneous albinism (OCA3) is a form of oculocutaneous albinism (OCA; see this term) characterized by rufous or brown albinism and occurring mainly in the African population.	Rare inborn errors of metabolism;Rare genetic eye disease;Rare genetic skin disease
Orphanet:79432	Oculocutaneous albinism type 2	OCA2;MC1R	2	Oculocutaneous albinism type 2 (OCA2) is a type of OCA (see this term) and the most common form of OCA seen in the African population, characterized by variable hypopigmentation of the skin and hair, numerous characteristic ocular changes and misrouting of the optic nerves at the chiasm.	Rare inborn errors of metabolism;Rare genetic eye disease;Rare genetic skin disease
Orphanet:79431	Oculocutaneous albinism type 1A	TYR	1	Oculocutaneous albinism type 1A (OCA1A) is the most severe form of OCA (see this term), where no melanin is produced, and is characterized by white hair and skin, blue, fully translucent irises, nystagmus and misrouting of the optic nerves.	Rare inborn errors of metabolism;Rare genetic eye disease;Rare genetic skin disease
Orphanet:79445	Pseudopseudohypoparathyroidism	GNAS	1	Pseudopseudohypoparathyroidism (pseudo-PHP) is a disease characterized by a constellation of clinical features collectively termed Albright hereditary osteodystrophy (AHO; see this term) but no evidence of resistance to parathyroid hormone (PTH), which is seen in other forms of pseudohypoparathyroidism (PHP; see this term).	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease;Rare genetic endocrine disease;Rare genetic renal disease
Orphanet:79444	Pseudohypoparathyroidism type 1C	GNAS	1	Pseudohypoparathyroidism type 1c (PHP1c) is a rare type of pseudohypoparathyroidism (PHP; see this term) characterized by resistance to parathyroid hormone (PTH) and other hormones, which manifests with hypocalcemia, hyperphosphatemia and elevated PTH levels, a constellation of clinical features collectively termed Albright's hereditary osteodystrophy (AHO; see this term), but normal activity of the stimulatory protein G (Gs alpha).	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease;Rare genetic endocrine disease;Rare genetic renal disease
Orphanet:79443	Pseudohypoparathyroidism type 1A	GNAS	1	Pseudohypoparathyroidism type 1A (PHP1a) is a type of pseudohypoparathyroidism (PHP; see this term) characterized by renal resistance to parathyroid hormone (PTH), resulting in hypocalcemia, hyperphosphatemia, and elevated PTH; resistance to other hormones including thydroid stimulating hormone (TSH), gonadotropins and growth-hormone-releasing hormone (GHRH); and a constellation of clinical features known as Albright hereditary osteodystrophy (AHO; see this term).	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease;Rare genetic endocrine disease;Rare genetic renal disease
Orphanet:79483	Phakomatosis cesioflammea	GNAQ;GNA11	2	NA	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:79484	Phakomatosis cesiomarmorata	GNA11	1	NA	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:79478	Griscelli syndrome type 3	MLPH;MYO5A	2	NA	Rare genetic eye disease;Rare genetic skin disease
Orphanet:79474	Atypical Werner syndrome	LMNA	1	 mutations, patients generally exhibit an aged appearance and common age-related disorders at earlier ages compared to the general population.	Rare genetic developmental defect during embryogenesis;Laminopathy
Orphanet:79477	Griscelli syndrome type 2	RAB27A	1	NA	Rare genetic immune disease;Rare genetic eye disease;Rare genetic skin disease
Orphanet:79476	Griscelli syndrome type 1	MYO5A	1	NA	Rare genetic eye disease;Rare genetic skin disease
Orphanet:79473	Porphyria variegata	PPOX	1	Variegate porphyria is a form of acute hepatic porphyria (see this term) characterized by the occurrence of neuro-visceral attacks with or without the presence of cutaneous lesions.	Rare genetic neurological disorder;Rare genetic skin disease;Rare genetic renal disease;Rare inborn errors of metabolism
Orphanet:79269	Sanfilippo syndrome type A	SGSH	1	NA	Rare genetic bone disease;Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:79257	GM1 gangliosidosis type 3	GLB1	1	GM1 gangliosidosis type 3 is a mild, chronic, adult form of GM1 gangliosidosis (see this term) characterized by onset generally during childhood or adolescence and by cerebellar dysfunction.	Rare genetic bone disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:79256	GM1 gangliosidosis type 2	GLB1	1	GM1 gangliosidosis type 2 is a clinically variable, infancy or childhood-onset form of GM1 gangliosidosis (see this term) characterized by normal early development and psychomotor regression between seven months and three years of age.	Rare genetic eye disease;Rare genetic bone disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:79255	GM1 gangliosidosis type 1	GLB1	1	GM1 gangliosidosis type 1 is the severe infantile form of GM1 gangliosidosis (see this term) with variable neurological and systemic manifestations.	Rare genetic eye disease;Rare genetic bone disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:79254	Classic phenylketonuria	PAH	1	Classical phenylketonuria is a severe form of phenylketonuria (PKU, see this term) an inborn error of amino acid metabolism characterized in untreated patients by severe intellectual deficit and neuropsychiatric complications.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:79259	Glycogen storage disease due to glucose-6-phosphatase deficiency type Ib	SLC37A4	1	Glycogenosis due to glucose-6-phosphatase deficiency (G6P) type b, or glycogen storage disease (GSD) type 1b, is a type of glycogenosis due to G6P deficiency (see this term).	Rare genetic immune disease;Rare genetic hepatic disease;Rare inborn errors of metabolism;Rare genetic renal disease
Orphanet:79258	Glycogen storage disease due to glucose-6-phosphatase deficiency type Ia	G6PC	1	Glycogenosis due to glucose-6-phosphatase deficiency (G6P) type a, or glycogen storage disease (GSD) type 1a, is a type of glycogenosis due to G6P deficiency (see this term).	Rare genetic hepatic disease;Rare inborn errors of metabolism;Rare genetic renal disease
Orphanet:79246	Pyruvate dehydrogenase phosphatase deficiency	PDP1	1	Pyruvate dehydrogenase phosphatase deficiency is a very rare subtype of pyruvate dehydrogenase deficiency (PDHD, see this term) characterized by lactic acidemia in the neonatal period.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:79253	Mild phenylketonuria	PAH	1	Mild phenylketonuria is a rare form of phenylketouria (PKU, see this term), an inborn error of amino acid metabolism, characterized by symptoms of PKU of mild to moderate severity.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:79240	Glycogen storage disease due to liver and muscle phosphorylase kinase deficiency	PHKB	1	A benign inborn error of glycogen metabolism. It is the mildest form of GSD due to PhK deficiency.	Rare genetic hepatic disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:79241	Biotinidase deficiency	BTD	1	A late-onset form of multiple carboxylase deficiency, an inborn error of biotin metabolism that, if untreated, is characterized by seizures, breathing difficulties, hypotonia, skin rash, alopecia, hearing loss and delayed development.	Rare genetic neurological disorder;Rare genetic skin disease;Rare inborn errors of metabolism
Orphanet:79239	Classic galactosemia	GALT	1	A life-threatening metabolic disease with onset in the neonatal period. Infants usually develop feeding difficulties, lethargy, and severe liver disease.	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility;Rare genetic hepatic disease;Rare genetic eye disease;Rare inborn errors of metabolism;Rare genetic renal disease
Orphanet:79244	Pyruvate dehydrogenase E2 deficiency	DLAT	1	A very rare form of pyruvate dehydrogenase deficiency (PDHD) characterized by variable lactic acidosis and neurological dysfunction, mainly appearing during childhood.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:79242	Holocarboxylase synthetase deficiency	HLCS	1	A life-threatening early-onset form of multiple carboxylase deficiency, an inborn error of biotin metabolism, that, if untreated, is characterized by vomiting, tachypnea, irritability, lethargy, exfoliative dermatitis, and seizures that can worsen to coma.	Rare genetic skin disease;Rare inborn errors of metabolism
Orphanet:79243	Pyruvate dehydrogenase E1-alpha deficiency	PDHA1	1	A disorder that is the most frequent form of pyruvate dehydrogenase deficiency (PDHD) characterized by variable lactic acidosis, impaired psychomotor development, hypotonia and neurological dysfunction.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:79299	Hyperinsulinism due to glucokinase deficiency	GCK	1	Hyperinsulism due to glucokinase deficiency (HIGCK) is a form of diazoxide-sensitive diffuse hyperinsulinism (see this term), caused by a lowered threshold for insulin release, characterized by an excessive/ uncontrolled insulin secretion (inappropriate for the level of glycemia) and recurrent episodes of profound hypoglycemia induced by fasting and protein rich meals, requiring rapid and intensive treatment to prevent neurological sequelae.	Rare inborn errors of metabolism;Rare genetic endocrine disease;Rare genetic developmental defect during embryogenesis
Orphanet:79301	Congenital bile acid synthesis defect type 1	HSD3B7	1	Congenital bile acid synthesis defect type 1 (BAS defect type 1) is the most common anomaly of bile acid synthesis (see this term) characterized by variable manifestations of progressive cholestatic liver disease, and fat malabsorption.	Rare inborn errors of metabolism;Rare genetic hepatic disease
Orphanet:79293	Familial LCAT deficiency	LCAT	1	Familial LCAT (lecithin-cholesterol acyltransferase) deficiency (FLD) is a form of lecithin-cholesterol acyltransferase deficiency (LCAT; see this term) characterized clinically by corneal opacities, hemolytic anemia, and renal failure, and biochemically by severely decreased HDL cholesterol and complete deficiency of the LCAT enzyme.	Rare inborn errors of metabolism;Rare genetic endocrine disease;Rare genetic eye disease;Rare genetic renal disease;Rare genetic hematologic disease
Orphanet:79292	Fish-eye disease	LCAT	1	Fish eye disease (FED) is a form of genetic LCAT (lecithin-cholesterol acyltransferase) deficiency (see this term) characterized clinically by corneal opacifications, and biochemically by significantly reduced HDL cholesterol and partial LCAT enzyme deficiency.	Rare inborn errors of metabolism;Rare genetic endocrine disease;Rare genetic eye disease;Rare genetic renal disease
Orphanet:79278	Autosomal erythropoietic protoporphyria	FECH	1	Erythropoietic protoporphyria (EPP) is an inherited disorder of the heme metabolic pathway characterized by accumulation of protoporphyrin in blood, erythrocytes and tissues, and cutaneous manifestations of photosensitivity.	Rare genetic skin disease;Rare genetic renal disease;Rare inborn errors of metabolism
Orphanet:79279	Alpha-N-acetylgalactosaminidase deficiency type 1	NAGA	1	A very rare and severe type of NAGA deficiency characterized by infantile neuroaxonal dystrophy.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:79280	Alpha-N-acetylgalactosaminidase deficiency type 2	NAGA	1	A very rare mild adult type of NAGA deficiency with the features of angiokeratoma corporis diffusum and mild sensory neuropathy.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:79281	Alpha-N-acetylgalactosaminidase deficiency type 3	NAGA	1	A rare clinically heterogeneous type of NAGA deficiency with developmental, neurologic and psychiatric manifestations presenting at an intermediate age.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:79282	Methylmalonic acidemia with homocystinuria, type cblC	MMACHC	1	 type methylmalonic acidemia with homocystinuria is a form of methylmalonic acidemia with homocystinuria (see this term), an inborn error of vitamin B12 (cobalamin) metabolism characterized by megaloblastic anemia, lethargy, failure to thrive, developmental delay, intellectual deficit and seizures.	Rare genetic neurological disorder;Rare genetic eye disease;Rare inborn errors of metabolism;Rare genetic hematologic disease;Rare genetic renal disease
Orphanet:79283	Methylmalonic acidemia with homocystinuria, type cblD	MMADHC	1	 type methylmalonic acidemia with homocystinuria is a form of methylmalonic acidemia with homocystinuria (see this term), an inborn error of vitamin B12 (cobalamin) metabolism characterized by variable biochemical, neurological and hematological manifestations.	Rare inborn errors of metabolism;Rare genetic hematologic disease
Orphanet:79284	Methylmalonic acidemia with homocystinuria type cblF	LMBRD1	1	 type methylmalonic acidemia with homocystinuria is a form of methylmalonic acidemia with homocystinuria (see this term), an inborn error of vitamin B12 (cobalamin) metabolism characterized by megaloblastic anemia, lethargy, failure to thrive, developmental delay, intellectual deficit and seizures.	Rare inborn errors of metabolism;Rare genetic hematologic disease
Orphanet:79270	Sanfilippo syndrome type B	NAGLU	1	NA	Rare genetic bone disease;Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:79271	Sanfilippo syndrome type C	HGSNAT	1	NA	Rare genetic bone disease;Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:79272	Sanfilippo syndrome type D	GNS	1	NA	Rare genetic bone disease;Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:79273	Hereditary coproporphyria	CPOX	1	Hereditary coproporphyria is a form of acute hepatic porphyria (see this term) characterized by the occurrence of neuro-visceral attacks and, more rarely, by the presence of cutaneous lesions.	Rare genetic neurological disorder;Rare genetic skin disease;Rare genetic renal disease;Rare inborn errors of metabolism
Orphanet:79276	Acute intermittent porphyria	HMBS	1	A rare, severe form of the acute hepatic porphyrias characterized by the occurrence of neuro-visceral attacks without cutaneous manifestations.	Rare genetic neurological disorder;Rare genetic skin disease;Rare genetic renal disease;Rare inborn errors of metabolism
Orphanet:79277	Congenital erythropoietic porphyria	UROS;GATA1	2	Congenital erythropoietic porphyria, or Günther disease, is a form of erythropoietic porphyria characterized by very severe and mutilating photodermatosis.	Rare genetic skin disease;Rare genetic renal disease;Rare inborn errors of metabolism;Rare genetic hematologic disease
Orphanet:79333	COG7-CDG	COG7	1	COG7-CDG is a congenital disorder of glycosylation characterised by dysmorphism, skeletal dysplasia, hypotonia, hepatosplenomegaly, jaundice, cardiac insufficiency, recurrent infections and epilepsy. To date, it has been described in two infants, both of whom died within the first three months of life. The syndrome is caused by a mutation in the gene encoding COG-7 (chromosome 16), a subunit of the oligomeric Golgi complex.	Rare genetic skin disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic cardiac disease;Rare inborn errors of metabolism
Orphanet:79332	B4GALT1-CDG	B4GALT1	1	 gene (localised to region q13 of chromosome 9) leading to a deficiency in the Golgi apparatus enzyme beta-1,4-galactosyl transferase.	Rare inborn errors of metabolism;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic hepatic disease
Orphanet:79330	MOGS-CDG	MOGS	1	 (2p13.1).	Rare genetic hepatic disease;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:79329	MGAT2-CDG	MGAT2	1	 (14q21).	Rare inborn errors of metabolism;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic cardiac disease
Orphanet:79328	ALG9-CDG	ALG9	1	 (11q23).	Rare genetic hepatic disease;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:79327	ALG1-CDG	ALG1	1	 (16p13.3).	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:79326	ALG2-CDG	ALG2	1	 (9q31.1). Transmission is autosomal recessive.	Rare genetic eye disease;Rare genetic hepatic disease;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:79325	ALG8-CDG	ALG8	1	 (11q14.1), resulting in a block in the initial step of protein glycosylation.	Rare genetic eye disease;Rare genetic gastroenterological disease;Rare genetic hepatic disease;Rare inborn errors of metabolism;Rare genetic neurological disorder;Rare genetic renal disease
Orphanet:79324	ALG12-CDG	ALG12	1	 (22q13.33).	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:79323	MPDU1-CDG	MPDU1	1	The CDG (Congenital Disorders of Glycosylation) syndromes are a group of autosomal recessive disorders affecting glycoprotein synthesis. CDG syndrome type If is characterised by psychomotor delay, seizures, failure to thrive, and cutaneous and ocular anomalies.	Rare inborn errors of metabolism;Rare genetic skin disease;Rare genetic neurological disorder
Orphanet:79322	DPM1-CDG	DPM1	1	The CDG (Congenital Disorders of Glycosylation) syndromes are a group of autosomal recessive disorders affecting glycoprotein synthesis. CDG syndrome type Ie is characterised by psychomotor delay, seizures, hypotonia, facial dysmorphism and microcephaly. Ocular anomalies are also very common.	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:79321	ALG3-CDG	ALG3	1	 (3q27.3).	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:79320	ALG6-CDG	ALG6	1	 (1p31.3).	Rare genetic gastroenterological disease;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:79319	MPI-CDG	MPI	1	 (15q24.1).	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic gastroenterological disease;Rare genetic hepatic disease;Rare inborn errors of metabolism
Orphanet:79318	PMM2-CDG	PMM2	1	PMM2-CDG is the most frequent form of congenital disorder of N-glycosylation and is characterized by cerebellar dysfunction, abnormal fat distribution, inverted nipples, strabismus and hypotonia. 3 forms of PMM2-CDG can be distinguished: the infantile multisystem type, late-infantile and childhood ataxia-intellectual disability type (3-10 yrs old), and the adult stable disability type. Infants usually develop ataxia, psychomotor delay and extraneurological manifestations including failure to thrive, enteropathy, hepatic dysfunction, coagulation abnormalities and cardiac and renal involvement. The phenotype is however highly variable and ranges from infants who die in the first year of life to mildly involved adults.	Rare genetic skin disease;Rare genetic hepatic disease;Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:79314	L-2-hydroxyglutaric aciduria	L2HGDH	1	L-2-hydroxyglutaric aciduria is a primarily neurological form of 2-hydroxyglutaric aciduria (see this term) characterized by psychomotor retardation, cerebellar ataxia and variable macrocephaly or epilepsy.	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:79315	D-2-hydroxyglutaric aciduria	D2HGDH;IDH2	2	D-2-hydroxyglutaric aciduria (D-2-HGA) is a rare clinically variable neurological form of 2-hydroxyglutaric aciduria (see this term) characterized biochemically by elevated D-2-hydroxyglutaric acid (D-2-HG) in the urine, plasma and cerebrospinal fluid.	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:79312	Vitamin B12-unresponsive methylmalonic acidemia type mut-	MUT	1	Vitamin B12-unresponsive methylmalonic acidemia type mut- is an inborn error of metabolism characterized by recurrent ketoacidotic comas or transient vomiting, dehydration, hypotonia and intellectual deficit, which does not respond to administration of vitamin B12.	Rare inborn errors of metabolism;Rare genetic renal disease
Orphanet:79310	Vitamin B12-responsive methylmalonic acidemia type cblA	MMAA	1	NA	Rare inborn errors of metabolism;Rare genetic renal disease
Orphanet:79311	Vitamin B12-responsive methylmalonic acidemia type cblB	MMAB	1	NA	Rare inborn errors of metabolism;Rare genetic renal disease
Orphanet:79306	Progressive familial intrahepatic cholestasis type 1	MYO5B;ATP8B1	2	PFIC1, a type of progressive familial intrahepathic cholestasis (PFIC, see this term), is an infantile hereditary disorder in bile formation that is hepatocellular in origin and associated with extrahepatic features.	Rare inborn errors of metabolism;Rare genetic hepatic disease
Orphanet:79304	Progressive familial intrahepatic cholestasis type 2	ABCB11	1	Progressive familial intrahepatic cholestasis type 2 (PFIC2), a type of progressive familial intrahepatic cholestasis (PFIC, see this term), is a severe, neonatal, hereditary disorder in bile formation that is hepatocellular in origin and not associated with extrahepatic features. Initially, PFIC2 was reported under the name Byler syndrome.	Rare inborn errors of metabolism;Rare genetic hepatic disease
Orphanet:79305	Progressive familial intrahepatic cholestasis type 3	ABCB4	1	Progressive familial intrahepatic cholestasis type 3 (PFIC3), a type of progressive familial intrahepatic cholestasis (PFIC, see this term), is a late-onset hereditary disorder in bile formation that is hepatocellular in origin. Onset may occur from infancy to young adulthood.	Rare inborn errors of metabolism;Rare genetic hepatic disease
Orphanet:79302	Congenital bile acid synthesis defect type 3	CYP7B1	1	Congenital bile acid synthesis defect type 3 (BAS defect type 3) is a severe anomaly of bile acid synthesis (see this term) characterized by severe neonatal cholestatic liver disease.	Rare inborn errors of metabolism;Rare genetic hepatic disease
Orphanet:79303	Congenital bile acid synthesis defect type 2	AKR1D1	1	Congenital bile acid synthesis defect type 2 (BAS defect type 2) is an anomaly of bile acid synthesis (see this term) characterized by severe and rapidly progressive cholestatic liver disease, and malabsorption of fat and fat-soluble vitamins.	Rare inborn errors of metabolism;Rare genetic hepatic disease
Orphanet:79351	3-phosphoglycerate dehydrogenase deficiency, infantile/juvenile form	PHGDH	1	3-Phosphoglycerate dehydrogenase deficiency (3-PGDH deficiency) is an autosomal recessive form of serine deficiency syndrome (see this term) characterized clinically in the few reported cases by congenital microcephaly, psychomotor retardation and intractable seizures in the infantile form and by absence seizures, moderate developmental delay and behavioral disorders in the juvenile form	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:79350	3-phosphoserine phosphatase deficiency	PSPH	1	3-Phosphoserine phosphatase deficiency is an extremely rare form of serine deficiency syndrome (see this term) characterized clinically by congenital microcephaly and severe psychomotor retardation in the single reported case to date, which was associated with Williams syndrome (see this term).	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:79345	Brachytelephalangic chondrodysplasia punctata	ARSE	1	Brachytelephalangic chondrodysplasia punctata (BCDP) is a form of non-rhizomelic chondrodysplasia punctata, a primary bone dysplasia, characterized by hypoplasia of the distal phalanges of the fingers, nasal hypoplasia, epiphyseal stippling appearing in the first year of life, as well as mild and non-rhizomelic shortness of the long bones.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare inborn errors of metabolism
Orphanet:85191	Singleton-Merten dysplasia	IFIH1;DDX58	2	Singleton-Merten dysplasia is characterized by dental dysplasia, progressive calcification of the thoracic aorta with stenosis, osteoporosis and expansion of the marrow cavities in hand bones. Additional features included generalized muscle weakness and atrophy, and chronic psoriasiform skin eruptions. It has been reported in four unrelated patients (male and female) and in a family with multiple affected members (male).	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic systemic or rheumatologic disease;Rare genetic immune disease
Orphanet:85193	Idiopathic juvenile osteoporosis	WNT3A;DKK1;WNT1	3	Idiopathic juvenile osteoporosis (IJO) is a primary condition of bone demineralization that presents with pain in the back and extremities, walking difficulties, multiple fractures, and radiological evidence of osteoporosis.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:85195	Familial expansile osteolysis	TNFRSF11A	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:85194	Spondylo-ocular syndrome	XYLT2	1	Spondylo-ocular syndrome is a very rare association of spinal and ocular manifestations that is characterized by dense cataracts, and retinal detachment along with generalized osteoporosis and platyspondyly. Mild craniofacial dysphormism has been reported including short neck, large head and prominent eyebrows.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic eye disease
Orphanet:85196	Nodulosis-arthropathy-osteolysis syndrome	MMP2;MMP14	2	NA	NA
Orphanet:85198	Dysspondyloenchondromatosis	COL2A1	1	Dysspondyloenchondromatosis is a rare skeletal dysplasia characterized by anisospondyly and multiple enchondromas in vertebrae and the metaphyseal and diaphyseal parts of long tubular bones, leading to kyphoscoliosis and lower limb asymmetry.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:85201	Genitopatellar syndrome	KAT6B	1	Genitopatellar syndrome is a rare congenital patellar anomaly syndrome characterized by patellar aplasia or hypoplasia associated with microcephaly, characteristic coarse facial features (microcephaly, bitemporal narrowing, large, broad nose with high nasal bridge, prominent cheeks and micro/retrognathia or prognathism), arthrogryposis of the hips and knees, urogenital abnormalities and intellectual deficiency.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:85200	Ischiovertebral syndrome	BMPER	1	Ischio-vertebral syndrome is a very rare, poorly-defined bone disease characterized by ischial aplasia or hypoplasia, vertebral anomalies (vertebral malsegmentation, kyphoscoliosis), and in some patients, non-distinctive facial dysmorphism.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:85202	Keutel syndrome	MGP	1	Keutel syndrome is characterised by diffuse cartilage calcification, brachytelephalangism, peripheral pulmonary artery stenoses and facial dysmorphism.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:85212	Fetal Gaucher disease	GBA	1	Fetal Gaucher disease is the perinatal lethal form of Gaucher disease (GD; see this term).	Rare inborn errors of metabolism;Rare genetic skin disease
Orphanet:85277	X-linked intellectual disability, Cantagrel type	NEXMIF	1	X-linked Mental retardation Cantagrel type is characterised by marked neonatal hypotonia, progressive quadriparesia, severely delayed developmental milestones (walking at 3 years of age), gastroesophageal reflux, stereotypic movements of the hands, esotropia and infantile autism.	Rare genetic neurological disorder
Orphanet:85278	Christianson syndrome	SLC9A6	1	Christianson syndrome is a very rare form of syndromic intellectual deficit characterized by microcephaly, severe developmental delay or regression, hypotonia, abnormal movements, and early-onset seizures.	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease;Rare genetic neurological disorder
Orphanet:85279	Syndromic X-linked intellectual disability due to JARID1C mutation	KDM5C	1	) gene encoding a JmjC-domain protein with histone demethylase activity.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:85282	MEHMO syndrome	EIF2S3	1	MEHMO syndrome is characterised by severe intellectual deficit, epilepsy, microcephaly, hypogenitalism, and obesity. Growth delay and diabetes are also present. To date, it has been described in seven boys, all of whom died within the first two years of life. The causative gene has been localised to the 21.1-22.13p region of the X chromosome and the syndrome appears to result from mitochondrial dysfunction.	Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease;Rare genetic neurological disorder
Orphanet:85284	BRESEK syndrome	MBTPS2	1	X-linked mental retardation, Reish type is characterised by Brain anomalies, severe mental Retardation, Ectodermal dysplasia, Skeletal deformities (vertebral anomalies, scoliosis, polydactyly), Ear/eye anomalies (maldevelopment, small optic nerves, low set and large ears with hearing loss) and Kidney dysplasia/hypoplasia (giving the acronym BRESEK syndrome).	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:85287	X-linked intellectual disability, Siderius type	PHF8	1	 gene, localised to the p11.21 region of the X chromosome.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:85288	X-linked intellectual disability, Stocco Dos Santos type	SHROOM4	1	 gene, localised to the Xp11.2 region.	Rare genetic neurological disorder
Orphanet:85293	X-linked intellectual disability, Cabezas type	CUL4B	1	An X-linked syndromic intellectual disability characterized by developmental delay, intellectual disability with significant speech impairment, and short stature in male patients. Variable additional clinical features have been associated, including macrocephaly, seizures, tremor, gait abnormalities, hypogonadism, truncal obesity, behavioral disturbances and unspecific facial dysmorphism.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:85295	HSD10 disease, atypical type	HSD17B10	1	NA	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:85294	X-linked epilepsy-learning disabilities-behavior disorders syndrome	SYN1	1	X-linked epilepsy-learning disabilities-behavior disorders syndrome is characterized by epilepsy, learning difficulties, macrocephaly, and aggressive behaviour. It has been described in males from a four-generation kindred. It is transmitted as an X-linked recessive trait and is likely to be caused by mutations in the gene encoding synapsin I (Xp11.3-q12).	Rare genetic neurological disorder
Orphanet:85328	X-linked intellectual disability, Turner type	HUWE1	1	X-linked intellectual disability, Turner type is characterised by moderate to severe intellectual deficit in boys and moderate intellectual deficit in girls. It has been described in 14 members from four generations of one family. Macrocephaly was reported and holoprosencephaly may also be present (two family members). The mode of transmission is X-linked semi-dominant.	Rare genetic neurological disorder
Orphanet:85329	X-linked intellectual disability-hypotonia-facial dysmorphism-aggressive behavior syndrome	AP1S2	1	X-linked intellectual disability-hypotonia-facial dysmorphism-aggressive behavior syndrome is characterised by severe intellectual deficit, hypotonia, mild facial dysmorphism, and aggressive behaviour. It has been described in 10 male members spanning four generations of one family. The facial dysmorphism includes a high forehead, prominent ears, and a small pointed chin. Height and head circumference are reduced. This disorder is transmitted as an X-linked recessive trait and the causative gene maps to Xp22.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:85335	Fried syndrome	AP1S2	1	Fried syndrome is a rare X-linked mental retardation (XLMR) syndrome characterized by psychomotor delay, intellectual deficit, hydrocephalus, and mild facial anomalies.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:85410	Oligoarticular juvenile idiopathic arthritis	PTPN22;STAT4;IL2RA;CD247;PTPN2;ANKRD55;IL2RB	7	Oligoarticular juvenile arthritis is the most common form of juvenile idiopathic arthritis (JIA), representing nearly 50% of cases.	
Orphanet:85414	Systemic-onset juvenile idiopathic arthritis	HLA-DRB1;MIF;IL6;LACC1	4	Systemic-onset juvenile idiopathic arthritis is marked by the severity of the extra-articular manifestations (fever, cutaneous eruptions) and by an equal sex ratio.	
Orphanet:85408	Rheumatoid factor-negative juvenile idiopathic arthritis	PTPN22;STAT4;IL2RA;CD247;PTPN2;ANKRD55;IL2RB	7	Rheumatoid factor-negative polyarthritis is a term used to describe a group of poorly defined heterogenous conditions that incorporates forms of rheumatoid factor-negative polyarthritis and forms of oligoarticular arthritis that become extensive in less than 6 months after onset.	
Orphanet:85442	Short stature-pituitary and cerebellar defects-small sella turcica syndrome	LHX4	1	 gene (1q25).	Rare genetic endocrine disease
Orphanet:85445	AA amyloidosis	SAA1	1	Secondary amyloidosis is a form of amyloidosis (see this term), that complicates chronic inflammatory disorders (mainly rheumatoid arthritis, see this term) and is characterized by the aggregation and deposition of amyloid fibrils composed of serum amyloid A protein, an acute phase reactant. Although spleen, suprarenal gland, liver and gut are frequent sites of amyloid deposition, the clinical picture is dominated by renal involvement.	
Orphanet:85453	X-linked reticulate pigmentary disorder	POLA1	1	X-linked reticulate pigmentary disorder is an extremely rare skin disease described in only four families to date and characterized in males by diffuse reticulate brown hyperpigmentated skin lesions developing in early childhood and a variety of systemic manifestations (recurrent pneumonia, corneal opacification, gastrointestinal inflammation, urethral stricture, failure to thrive, hypohidrosis, digital clubbing, and unruly hair and flared eyebrows), while in females, there is only cutaneous involvement with the development in early childhood of localized brown hyperpigmented skin lesions following the lines of Blaschko. This disease was first considered as a cutaneous amyloidosis, but amyloid deposits are an inconstant feature.	Rare genetic skin disease;Rare genetic eye disease;Rare genetic systemic or rheumatologic disease;Rare genetic immune disease
Orphanet:86788	X-linked severe congenital neutropenia	WAS	1	 gene, encoding the WASP protein.	Rare genetic immune disease
Orphanet:86309	DPAGT1-CDG	DPAGT1	1	 (11q23.3).	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:85448	AGel amyloidosis	GSN	1	A rare, systemic amyloidosis characterized by a triad of ophthalmologic, neurologic and dermatologic findings due to the deposition of gelsolin amyloid fibrils in these tissues. Clinical manifestations include corneal lattice dystrophy, cranial neuropathy, especially affecting the facial nerve, bulbar signs, cutis laxa, increased skin fragility, and less commonly peripheral neuropathy and renal failure.	Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic systemic or rheumatologic disease
Orphanet:85447	ATTRV30M amyloidosis	TTR	1	Familial amyloid polyneuropathy (FAP) or transthyretin (TTR) amyloid polyneuropathy is a progressive sensorimotor and autonomic neuropathy of adulthood onset. Weight loss and cardiac involvement are frequent; ocular or renal complications may also occur.	Rare genetic neurological disorder;Rare genetic systemic or rheumatologic disease
Orphanet:85451	ATTRV122I amyloidosis	TTR	1	Transthyretin (TTR)-related familial amyloidotic cardiomyopathy is a hereditary TTR-related systemic amyloidosis (ATTR) with predominant cardiac involvement resulting from myocardial infiltration of abnormal amyloid protein.	Rare genetic cardiac disease;Rare genetic systemic or rheumatologic disease
Orphanet:86812	Autosomal recessive limb-girdle muscular dystrophy type 2K	POMT1	1	A form of limb-girdle muscular dystrophy characterized by the onset of slowly progressive proximal muscle weakness during childhood (with fatigue and difficulty running and climbing stairs) and developmental delay. Mild intellectual deficit and microcephaly, without any obvious structural brain abnormality, are found in all patients. Mild pseudohypertrophy and joint contractures of the ankles have also been reported.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:86813	Helicoid peripapillary chorioretinal degeneration	TEAD1	1	Helicoid peripapillary chorioretinal degeneration is a rare autosomal dominantly inherited chorioretinal degeneration disease, presenting at birth or infancy, characterized by progressive bilateral retinal and choroidal atrophy, appearing as lesions on the optic nerve and peripheral ocular fundus and leading to central vision loss. Congenital anterior polar cataracts are sometimes associated with this disease.	Rare genetic eye disease
Orphanet:86814	Benign adult familial myoclonic epilepsy	SAMD12;CTNND2;CNTN2;ADRA2B	4	Benign adult familial myoclonic epilepsy (BAFME) is an inherited epileptic syndrome characterized by cortical hand tremors, myoclonic jerks and occasional generalized or focal seizures with a non-progressive or very slowly progressive disease course, and no signs of early dementia or cerebellar ataxia.	Rare genetic neurological disorder
Orphanet:86815	Aplasia of lacrimal and salivary glands	FGF10	1	A rare autosomal dominant disorder characterized by aplasia, atresia or hypoplasia of the lacrimal and salivary glands leading to varying features since infancy such as recurrent eye infections, irritable eyes, epiphora, xerostomia, dental caries, dental erosion and oral inflammation.	Rare genetic eye disease
Orphanet:86820	Familial avascular necrosis of femoral head	TRPV4;COL2A1	2	Avascular necrosis of femoral head (ANFH) is a severely disabling disease characterised by progressive groin pain, a limping gait, leg length discrepancy, collapse of the subchondral bone, limitation of hip function and eventual degeneration of the hip joint requiring total hip arthroplasty.	Rare genetic bone disease
Orphanet:512017	Chronic lymphoproliferative disorder of natural killer cells	STAT3	1	NA	
Orphanet:86816	Congenital analbuminemia	ALB	1	Congenital analbuminemia (CAA) is characterized by the absence or dramatic reduction of circulating human serum albumin (HSA).	
Orphanet:86817	Hemolytic anemia due to adenylate kinase deficiency	AK1	1	Hemolytic anemia due to adenylate kinase deficiency is a rare hemolytic anemia due to an erythrocyte nucleotide metabolism disorder characterized by moderate to severe chronic nonspherocytic hemolytic anemia that may require regular blood transfusions and/or splenectomy and may be associated with psychomotor impairment.	Rare genetic hematologic disease
Orphanet:86818	Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome	AMMECR1;ACSL4;AMMECR1;KCNE5	4	.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder;Rare chromosomal anomaly;Rare genetic hematologic disease
Orphanet:86819	Atrichia with papular lesions	HR	1	A rare inherited form of alopecia characterized by irreversible hair loss during the neonatal period on all hear-bearing areas of the body, later associated with the development of papular lesions all over the body and preferentially on the face and extensor surfaces of the extremities.	Rare genetic skin disease
Orphanet:86841	Myelodysplastic syndrome associated with isolated del(5q) chromosome abnormality	RPS14	1	NA	
Orphanet:86839	Refractory anemia with excess blasts	TET2	1	Refractory anemia with excess blasts (RAEB) is a frequent severe subtype of myelodysplastic syndrome (MDS; see this term) characterized by cytopenias with unilineage or multilineage dysplasia and 5% to 19% blasts in bone marrow or blood.	
Orphanet:512103	Autosomal recessive epidermolytic ichthyosis	KRT10	1	NA	Rare genetic skin disease
Orphanet:86834	Juvenile myelomonocytic leukemia	RRAS;PTPN11;KRAS;NF1;NRAS;CBL	6	NA	
Orphanet:86830	Chronic myeloproliferative disease, unclassifiable	PDGFRB	1	Chronic myeloproliferative disease, unclassifiable is a hematological neoplasm characterized by clonal proliferation of myeloid precursors in the bone marrow, blood and other tissues (spleen, liver), with clinical, morphological and molecular features of myeloproliferative neoplasms (MPN), failing to meet criteria of a specific MPN. The presentation is nonspecific and variable and often includes leukocytosis, thrombocytosis and anemia. Splenomegaly, hepatomegaly as well as fatigue, malaise or weight loss may appear in advanced stages.	
Orphanet:86829	Chronic neutrophilic leukemia	CSF3R	1	NA	
Orphanet:512260	Congenital cerebellar ataxia due to RNU12 mutation	RNU12	1	NA	Rare genetic neurological disorder
Orphanet:86849	Acute basophilic leukemia	MYB;GATA1	2	NA	
Orphanet:86845	Acute myeloid leukaemia with myelodysplasia-related features	TET2	1	NA	
Orphanet:86872	T-cell large granular lymphocyte leukemia	STAT3	1	T-cell large granular lymphocyte leukemia (T-cell LGL leukemia) is a lymphoproliferative malignancy that arises from the mature T-cell (CD3+) lineage.	
Orphanet:79503	Ichthyosis hystrix of Curth-Macklin	KRT1	1	Ichthyosis hystrix of Curth-Macklin (IHCM) is a rare type of keratinopathic ichthyosis (see this term) that is characterized by the presence of severe hyperkeratotic lesions and palmoplantar keratoderma (PPK, see this term).	Rare genetic skin disease
Orphanet:79506	Cholesterol-ester transfer protein deficiency	APOC3;CETP	2	NA	Rare inborn errors of metabolism;Rare genetic endocrine disease
Orphanet:79495	X-linked congenital generalized hypertrichosis	SOX3	1	X-linked congenital generalized hypertrichosis is an extremely rare type of hypertrichosis lanuginosa congenita, a congenital skin disease, which is characterized by hair overgrowth on the entire body in males, and mild and asymmetric hair overgrowth in females. It is associated with a mild facial dysmorphism (anterverted nostrils, moderate prognathism), and, in a kindred, it was also associated with dental anomalies and deafness.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:79499	Autosomal dominant deafness-onychodystrophy syndrome	ATP6V1B2	1	Dominant deafness-onychodystrophy (DDOD) syndrome is a multiple congenital anomalies syndrome characterized by congenital hearing impairment, small or absent nails on the hands and feet, and small terminal phalanges.	Rare genetic neurological disorder;Rare genetic eye disease;Genetic otorhinolaryngologic disease;Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:79500	DOORS syndrome	TBC1D24	1	A rare multiple congenital anomalies-intellectual disability syndrome characterized by sensorineural hearing loss (deafness), onychodystrophy, osteodystrophy, mild to profound intellectual disability, and seizures.	Rare genetic neurological disorder;Rare genetic eye disease;Genetic otorhinolaryngologic disease;Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:79501	Punctate palmoplantar keratoderma type 1	COL14A1;AAGAB	2	Punctate palmoplantar keratoderma type I (PPKP1), also known as Buschke-Fischer-Brauer syndrome, is a very rare hereditary skin disease characterized by irregularly distributed epidermal hyperkeratosis of the palms and soles with wide variation among patients..	Rare genetic skin disease
Orphanet:79665	Gardner syndrome	APC	1	Gardner syndrome is a severe form of familial adenomatous polyposis characterized by multiple adenomas in the colon and rectum associated with prominent extracolonic features including osteomas and multiple skin and soft tissue tumors.	Rare genetic tumor;Rare genetic gastroenterological disease;Inherited cancer-predisposing syndrome;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:82004	Ehlers-Danlos syndrome with periventricular heterotopia	FLNA	1	NA	NA
Orphanet:79643	Autosomal recessive hyperinsulinism due to SUR1 deficiency	ABCC8	1	A rare, congenital, isolated hyperinsulinism disorder characterized by neonatal presentation of severe refractory hypoglycemia in the first two days of life, with limited response to medical management, sometimes requiring pancreatic resection. Newborns are often large for gestational age with mild to moderate hepatomegaly and diffuse form of hyperinsulinism due to SUR1 deficiency. Persistent hypoglycemia, hyperglycemia and type1 diabetes mellitus may develop later in life. Life-threatening hypoglycemic coma or status epilepticus have also been associated.	Rare genetic endocrine disease;Rare genetic developmental defect during embryogenesis
Orphanet:79651	Mild hyperphenylalaninemia	PAH	1	Mild hyperphenylalaninemia (HPA) is a rare form of phenylketonuria (see this term), an inborn error of amino acid metabolism, characterized by mild symptoms of HPA.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:79644	Autosomal recessive hyperinsulinism due to Kir6.2 deficiency	KCNJ11	1	A rare, congenital, isolated hyperinsulinism disorder characterized by neonatal presentation of severe refractory hypoglycemia in the first two days of life, with limited response to medical management, sometimes requiring pancreatic resection. Newborns are often large for gestational age with mild to moderate hepatomegaly and diffuse form of hyperinsulinism due to Kir6.2 deficiency. Persistent hypoglycemia, hyperglycemia and type1 diabetes mellitus may develop later in life. Life-threatening hypoglycemic coma or status epilepticus have also been associated.	Rare genetic endocrine disease;Rare genetic developmental defect during embryogenesis
Orphanet:83330	Proximal spinal muscular atrophy type 1	SMN2;NAIP;SMN1	3	Proximal spinal muscular atrophy type 1 (SMA1) is a severe infantile form of proximal spinal muscular atrophy (see this term) characterized by severe and progressive muscle weakness and hypotonia resulting from the degeneration and loss of the lower motor neurons in the spinal cord and the brain stem nuclei.	Rare genetic neurological disorder
Orphanet:83419	Proximal spinal muscular atrophy type 3	SMN2;NAIP;SMN1	3	Proximal spinal muscular atrophy type 3 (SMA3) is a relatively mild form of proximal spinal muscular atrophy (see this term) characterized by muscle weakness and hypotonia resulting from the degeneration and loss of the lower motor neurons in the spinal cord and the brain stem nuclei.	Rare genetic neurological disorder
Orphanet:83420	Proximal spinal muscular atrophy type 4	SMN2;SMN1	2	Proximal spinal muscular atrophy type 4 (SMA4) is the adult-onset form of proximal spinal muscular atrophy (see this term) characterized by muscle weakness and hypotonia resulting from the degeneration and loss of the lower motor neurons in the spinal cord and the brain stem nuclei.	Rare genetic neurological disorder
Orphanet:83418	Proximal spinal muscular atrophy type 2	SMN2;NAIP;SMN1	3	Proximal spinal muscular atrophy type 2 (SMA2) is a chronic infantile form of proximal spinal muscular atrophy (see this term) characterized by muscle weakness and hypotonia resulting from the degeneration and loss of the lower motor neurons in the spinal cord and the brain stem nuclei.	Rare genetic neurological disorder
Orphanet:83469	Desmoplastic small round cell tumor	WT1;EWSR1	2	An aggressive soft tissue cancer that typically arises in serous lined surfaces of the abdominal or pelvic peritoneum, and spreads to the omentum, lymph nodes and hematogenously disseminates especially to the liver. Extraserous primary location has been reported in exceptional cases.	
Orphanet:83465	Narcolepsy type 2	HCRT;HLA-DRB1;HLA-DQB1;ZNF365	4	A disorder that is characterized by excessive day-time sleepiness associated with uncontrollable sleep urges and sometimes paralysis at sleep, hypnagogic hallucinations and automatic behavior.	
Orphanet:83473	Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome	PIK3R2;PIK3R2;CCND2;AKT3	4	A syndrome that is characterized by megalencephaly, polymicrogyria, and hydrocephalus with variable polydactyly. It has been described in six unrelated patients. Intellectual deficit or slow development is also present. The mode of inheritance of this syndrome is unknown since all cases were sporadic.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:83472	CAMOS syndrome	ZNF592;WDR73	2	A disorder that is characterised by the association of a non-progressive congenital ataxia, severe intellectual deficit, optic atrophy and structural anomalies of the skin vessels. It has been described in five children from a large consanguineous Lebanese family. Short stature and microcephaly were also reported. Transmission is autosomal recessive.	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:83463	Microtia	HOXA2	1	A congenital malformation of the external ear, seen more frequently in males, that occurs sporadically or is inherited, that is characterized by unilateral (79-93% of cases, 60% of which involve the right ear) or bilateral small and abnormally shaped auricles and that is often associated with atresia or stenosis of the ear canal, attention deficit disorders and delayed language development. The variation in auricle size ranges from grade I, where the auricle is simply smaller than normal, to grade IV, also known as anotia, where there is a complete absence of the external ear and of the auditory canal.	Rare genetic developmental defect during embryogenesis;Genetic otorhinolaryngologic disease
Orphanet:83461	Congenital primary aphakia	FOXE3	1	 gene were identified in three affected siblings born to consanguineous parents.	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:83454	Glomuvenous malformation	GLMN	1	Glomuvenous malformations (GVMs) are hereditary vascular malformations characterized by the presence of small, multifocal bluish-purple venous lesions involving the skin.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:83620	Enteric anendocrinosis	NEUROG3	1	A very rare genetic gastroenterological disease characterized by severe malabsorptive diarrhea (requiring parenteral nutrition and disappearing at fasting) due to a lack of intestinal enteroendocrine cells. It is associated with early-onset (within the first weeks of life) dehydration, metabolic acidosis and diabetes mellitus (that can develop until late childhood). Patient may display various degrees of pancreatic insufficiency that does not explain diarrhea, as it is not reduced with pancreatic enzyme supplementation. Central hypogonadism (developing in the second decade), as well as an association with celiac disease have been reported.	Rare genetic gastroenterological disease
Orphanet:84081	Senior-Boichis syndrome	DCDC2;TMEM67	2	A syndrome that consists of the association of congenital nephronophthisis leading to renal failure, and hepatic fibrosis. It has been described in five members of one family, two of whom died from renal failure. The association of Boichis syndrome with tapetoretinal degeneration and intellectual deficit has also been reported in one family: the so-called Senior-Boichis syndrome could be in fact the same entity, and was later reported in a 12 year-old child.	Rare genetic renal disease;Ciliopathy
Orphanet:84090	Fibronectin glomerulopathy	FN1	1	A primary glomerular disease characterized by proteinuria, type IV renal tubular acidosis, microscopic hematuria and hypertension that may lead to end-stage renal failure in the second to sixth decade of life.	Rare genetic renal disease
Orphanet:84064	Syndromic diarrhea	TTC37;SKIV2L	2	A rare gastroenterologic disease manifesting as intractable diarrhea in the first month of life with failure to thrive and associated with facial dysmorphism, hair abnormalities, and, in some cases, immune disorders and intrauterine growth restriction.	Rare genetic gastroenterological disease;Rare genetic systemic or rheumatologic disease;Rare genetic hepatic disease;Rare genetic immune disease
Orphanet:513436	Autosomal recessive spastic paraplegia type 78	ATP13A2	1	NA	Rare genetic neurological disorder
Orphanet:83639	Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency	PIGM;PIGW	2	 and blocks mannosylation of glycosylphosphatidylinositol (GPI), leading to partial but severe deficiency of GPI.	Rare genetic hematologic disease;Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:513456	Intellectual disability-seizures-abnormal gait-facial dysmorphism syndrome	WDR26	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:83648	NA	OFD1	1	NA	NA
Orphanet:83642	Microcytic anemia with liver iron overload	SLC11A2	1	A congenital hypochromic microcytic anemia with progressive liver iron overload paradoxically associated with normal to moderately elevated serum ferritin levels has been described in three unrelated patients.	Rare inborn errors of metabolism;Rare genetic hematologic disease
Orphanet:85163	Hypomyelination-congenital cataract syndrome	FAM126A	1	Hypomyelination-congenital cataract is characterized by the onset of cataract either at birth or in the first two months of life, delayed psychomotor development by the end of the first year of life and moderate intellectual deficit.	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:85164	Camptodactyly-tall stature-scoliosis-hearing loss syndrome	FGFR3	1	Camptodactyly-tall stature-scoliosis-hearing loss syndrome is characterised by camptodactyly, tall stature, scoliosis, and hearing loss (CATSHL). It has been described in around 30 individuals from seven generations of the same family. The syndrome is caused by a missense mutation in the FGFR3 gene, leading to a partial loss of function of the encoded protein, which is a negative regulator of bone growth.	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:85146	Neurogenic scapuloperoneal syndrome, Kaeser type	DES	1	NA	Rare genetic neurological disorder
Orphanet:85128	Bothnia retinal dystrophy	RLBP1	1	Bothnia retinal dystrophy is a rare form of retinal dystrophy, seen mostly in Northern Sweden, presenting in early childhood with night blindness and progressive maculopathy with a decrease in visual acuity, eventually leading to blindness by adulthood. Retinal degeneration, without obvious bone spicule formation, accompanied by affected visual fields and the typical presence of retinitis punctata albescens (see this term) in the posterior pole are also noted.	Rare genetic eye disease
Orphanet:85136	Cystic leukoencephalopathy without megalencephaly	NDUFA2;RNASET2	2	Cystic leukoencephalopathy without megalencephaly is characterised by non-progressive leukoencephalopathy, bilateral cysts in the anterior part of the temporal lobe, cerebral white matter anomalies and severe psychomotor impairment. Less than 50 patients have been described in the literature so far. Inheritance is most likely autosomal recessive.	Rare genetic neurological disorder
Orphanet:85110	Familial encephalopathy with neuroserpin inclusion bodies	SERPINI1	1	A rare serpinopathy characterized by progressive myoclonus epilepsy and/or pre-senile dementia with prominent frontal-lobe features and relative sparing of recall memory. In addition, other neurological manifestations like cerebellar symptoms and pyramidal signs may be present. Age of onset is variable, the disease having been reported in children as well as elderly patients. Neuropathological examination reveals the typical neuronal inclusions of mutated neuroserpin (Collins bodies).	Rare genetic neurological disorder;Serpinopathy
Orphanet:85112	Palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome	RSPO1	1	Palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome is characterised by sex reversal in males with a 46, XX (SRY-negative) karyotype, palmoplantar hyperkeratosis and a predisposition to squamous cell carcinoma. To date, five cases (four of whom were brothers) have been described. The aetiology is unknown.	Rare genetic gynecological and obstetrical diseases;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease;Rare genetic skin disease
Orphanet:84132	Desmin-related myopathy with Mallory body-like inclusions	SELENON	1	NA	Rare genetic neurological disorder
Orphanet:85186	Endosteal sclerosis-cerebellar hypoplasia syndrome	POLR3B	1	Endosteal sclerosis-cerebellar hypoplasia syndrome is characterized by congenital cerebellar hypoplasia, endosteal sclerosis, hypotonia, ataxia, mild to moderate developmental delay, short stature, hip dislocation, and tooth eruption disturbances. It has been described in four patients. Less common manifestations are microcephaly, strabismus, nystagmus, optic atrophy, and dysarthria. It is appears to be transmitted as an autosomal recessive trait.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic neurological disorder
Orphanet:85182	Diaphyseal medullary stenosis-bone malignancy syndrome	MTAP	1	Diaphyseal medullary stenosis with malignant fibrous histiocytoma is a very rare autosomal dominant bone dysplasia/cancer syndrome characterized clinically by bone infarctions, cortical growth abnormalities, pathological fractures, and development of bone sarcoma (malignant fibrous histiocytoma).	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic tumor
Orphanet:85179	Infantile osteopetrosis with neuroaxonal dysplasia	OSTM1	1	This syndrome is characterized by osteopetrosis, agenesis of the corpus callosum, cerebral atrophy and a small hippocampus.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:85173	IMAGe syndrome	CDKN1C	1	nital anomalies. It has been described in less than 20 cases. The patients also present with dysmorphic features (frontal bossing, broad nasal bridge, low-set ears). In boys, genital anomalies include bilateral cryptorchidism, hypospadias, micropenis, and hypogonadotropic hypogonadism. This syndrome is likely to be transmitted as an autosomal recessive trait.	Rare genetic urogenital disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic endocrine disease
Orphanet:85169	Familial digital arthropathy-brachydactyly	TRPV4	1	Familial digital arthropathy-brachydactyly is characterised by the association of arthropathy of interphalangeal, metacarpophalangeal and metatarsophalangeal joints with brachydactyly of the middle and distal phalanges. It has been described in numerous members from five generations of one large family. Inheritance is autosomal dominant.	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:85167	Spondylometaphyseal dysplasia-cone-rod dystrophy syndrome	PCYT1A	1	Spondylometaphyseal dysplasia-cone-rod dystrophy syndrome is characterised by the association of spondylometaphyseal dysplasia (marked by platyspondyly, shortening of the tubular bones and progressive metaphyseal irregularity and cupping), with postnatal growth retardation and progressive visual impairment due to cone-rod dystrophy. So far, it has been described in eight individuals. Transmission appears to be autosomal recessive.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:85166	Platyspondylic dysplasia, Torrance type	COL2A1	1	 gene. Although PLSD-T is generally lethal, survival to adulthood has been reported in two families.	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:85165	Severe achondroplasia-developmental delay-acanthosis nigricans syndrome	FGFR3	1	 gene; 4p16.3).	Rare genetic bone disease;Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:97244	Rigid spine syndrome	ACTA1;SELENON	2	Rigid spine syndrome (RSS) is a slowly progressive childhood-onset congenital muscular dystrophy (see this term) characterized by contractures of the spinal extensor muscles associated with abnormal posture (limitation of neck and trunk flexure), progressive scoliosis of the spine, early marked cervico-axial muscle weakness with relatively preserved strength and function of the extremities and progressive respiratory insufficiency.	Rare genetic neurological disorder
Orphanet:97249	Pontocerebellar hypoplasia type 3	PCLO	1	Pontocerebellar hypoplasia type 3 (PCH3), also known as cerebellar atrophy with progressive microcephaly (CLAM) is a rare form of pontocerebellar hypoplasia (see this term) with autosomal recessive transmission characterized neonatally by hypotonia and impaired swallowing and from infancy onward by seizures, optic atrophy and short stature, but none of the clinical findings are specific for PCH3.	Rare genetic eye disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:97279	Insulinoma	MEN1	1	Insulinoma is the most common type of functioning pancreatic neuroendocrine tumor (see this term) characterized most commonly by a solitary, small pancreatic lesion that causes hyperinsulinemic hypoglycemia.	
Orphanet:97286	Carney-Stratakis syndrome	SDHB;SDHC;SDHD	3	Carney-Stratakis syndrome is a recently described familial syndrome characterized by gastrointestinal stromal tumors (GIST) and paragangliomas, often at multiple sites.	Rare genetic endocrine disease;Rare genetic tumor
Orphanet:97297	Bohring-Opitz syndrome	KLHL7;ASXL1	2	Bohring-Opitz syndrome is characterised by intrauterine growth retardation (IUGR), failure to thrive, facial dysmorphism (prominent metopic suture and forehead nevus flammeus, a low frontal and temporal hairline with hirsutism, puffy cheeks, upslanting palpebral fissures, exophthalmos, hypertelorism, cleft lip and palate, retrognathia and low set ears), flexion deformities of the elbows and wrists, camptodactyly, ulnar deviation of the fingers, foot anomalies and severe developmental delay. Less than 20 patients have been described so far. Although the large majority of reported cases occurred sporadically, autosomal recessive inheritance has also been reported.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:97338	Melanoma of soft tissue	EWSR1;ATF1;CREB1	3	NA	
Orphanet:97346	ADan amyloidosis	ITM2B	1	A rare, neurodegenerative disease characterized by progressive cataracts, hearing loss, cerebellar ataxia, paranoid psychosis and dementia. Neuropathological features are diffuse atrophy of all parts of the brain, chronic diffuse encephalopathy and the presence of extremely thin and almost completely demyelinated cranial nerves.	Rare genetic neurological disorder;Rare genetic systemic or rheumatologic disease
Orphanet:97345	ABri amyloidosis	ITM2B	1	A rare, neurodegenerative disease characterized by progressive cognitive impairment, spastic tetraparesis, and cerebellar ataxia resulting from amyloid deposits in the brain. Spasticity with increased deep tendon reflexes and tone are early symptoms, muscular rigidity evolves later. Progressive mental deterioration usually starts with apathy and impaired memory with progression to complete disorientation.	Rare genetic neurological disorder;Rare genetic systemic or rheumatologic disease
Orphanet:97362	Renal hypoplasia, bilateral	PAX2;PBX1	2	Bilateral renal hypoplasia is a form of renal hypoplasia (see this term), a renal developmental anomaly in which both kidneys are small and have a deficit in the number of nephrons present.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis
Orphanet:97363	Unilateral multicystic dysplastic kidney	HNF1B	1	Unilateral multicystic dysplastic kidney is the form of multicystic dysplastic kidney (MCDK, see this term), a congenital anomaly of the kidney and urinary tract (CAKUT), in which one kidney is large, distended by multiple cysts, and non-functional.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis
Orphanet:97364	Bilateral multicystic dysplastic kidney	HNF1B	1	Bilateral multicystic dysplastic kidney (MCDK) is a lethal form of multicystic dysplastic kidney (MCDK, see this term), a congenital anomaly of the kidney and urinary tract (CAKUT), in which both kidneys are large, distended by non-communicating multiple cysts and non-functional.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis
Orphanet:97369	Renal tubular dysgenesis of genetic origin	ACE;AGT;REN;AGTR1	4	NA	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis
Orphanet:97548	Right sided atrial isomerism	GDF1	1	NA	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis
Orphanet:96191	Paternal uniparental disomy of chromosome 6	HYMAI;PLAGL1	2	Paternal uniparental disomy of chromosome 6 is an uniparental disomy of paternal origin characterized by intrauterine growth retardation, transient neonatal diabetes mellitus, and macroglossia.	Rare chromosomal anomaly
Orphanet:96184	Temple syndrome due to maternal uniparental disomy of chromosome 14	MEG3;DLK1;RTL1	3	Maternal uniparental disomy of chromosome 14 is a rare chromosomal anomaly characterized by prenatal and postnatal growth retardation, hypotonia, motor delay, early puberty, obesity, short adult stature, small hands and feet, mild intellectual disability, and mild dysmorphic facial features (frontal bossing, short nose with wide nasal tip, micrognathia, high palate, short philtrum).	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease;Rare chromosomal anomaly
Orphanet:96253	Cushing disease	CDH23;USP8	2	Cushing disease (CD) is the most common cause of endogenous Cushing syndrome (CS; see this term) and is due to pituitary chronic over-secretion of ACTH by a pituitary corticotroph adenoma.	Rare genetic endocrine disease
Orphanet:96266	Leydig cell hypoplasia due to partial LH resistance	LHCGR	1	NA	Genetic infertility;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease
Orphanet:96265	Leydig cell hypoplasia due to complete LH resistance	LHCGR	1	NA	Genetic infertility;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease
Orphanet:96334	Kagami-Ogata syndrome due to paternal uniparental disomy of chromosome 14	MEG3;DLK1;RTL1	3	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare chromosomal anomaly
Orphanet:97234	Glycogen storage disease due to phosphoglycerate mutase deficiency	PGAM2	1	Muscle phosphoglycerate mutase deficiency (PGAMD) is a metabolic myopathy characterised by exercise-induced cramp, myoglobinuria, and presence of tubular aggregates in the muscle biopsy. Serum creatine kinase (CK) levels are increased between episodes of myoglobinuria. Less than 50 cases have been described so far. The disease is due to an anomaly in one of the last steps of glycolysis. The enzymatic defect in PGAMD is caused by mutations in the cDNA coding for the M-isoform of PGAM. Residual PGAM activity in the muscles of patients (2%-6%) is due to activity of the B-isoform. Transmission is autosomal recessive. Differential diagnosis includes muscle phosphorylase deficiency (McArdle disease) and phosphofructokinase deficiency (PFKD) (see these terms).	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:97238	Rippling muscle disease	CAV3	1	Rippling muscle disease is a rare, genetic, neuromuscular disorder characterized by muscle hyperirritability triggered by stretch, percussion or movement. Patients present wave-like, electrically-silent muscle contractions (rippling), muscle mounding, painful muscle stiffness and muscle hypertrophy, usually with elevated serum creatine kinase.	Rare genetic neurological disorder
Orphanet:97239	Reducing body myopathy	FHL1	1	Reducing body myopathy (RBM) is a rare muscle disorder marked by progressive muscle weakness and the presence of characteristic inclusion bodies in affected muscle fibres.	Rare genetic neurological disorder
Orphanet:97240	Zebra body myopathy	ACTA1	1	) gene may be involved.	Rare genetic neurological disorder
Orphanet:97229	Riboflavin transporter deficiency	SLC52A3;SLC52A2	2	Riboflavin transporter deficiency (RTD) is a progressive motor neuron disorder characterized by respiratory insufficiency, sensorineural deafness and progressive ponto-bulbar palsy.	Genetic otorhinolaryngologic disease;Rare genetic neurological disorder
Orphanet:97231	Ligneous conjunctivitis	PLG	1	Ligneous conjunctivitis (LC) is a rare form of chronic conjunctivitis characterised by the recurrent formation of pseudomembranous lesions most commonly on the palpebral surfaces. It is most frequently reported as a clinical manifestation of severe homozygous or compound-heterozygous hypoplasminogenemia (see this term).	Rare genetic eye disease
Orphanet:97927	OBSOLETE: Peripheral resistance to thyroid hormones	THRB;THRA	2	NA	NA
Orphanet:97685	17q11 microdeletion syndrome	NF1	1	17q11 microdeletion syndrome is a rare severe form of neurofibromatosis type 1 (NF1; see this term) characterized by mild facial dysmorphism, developmental delay, intellectual disability, increased risk of malignancies, and a large number of neurofibromas.	Rare chromosomal anomaly;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic skin disease;Rare genetic renal disease;Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic tumor
Orphanet:95702	Cytomegalic congenital adrenal hypoplasia	NR0B1	1	NA	Rare genetic endocrine disease;Rare genetic gynecological and obstetrical diseases;Genetic infertility
Orphanet:95716	Familial thyroid dyshormonogenesis	SLC5A5;TPO;DUOX2;DUOXA2;TG;IYD	6	Familial thyroid dyshormonogenesis is a type of primary congenital hypothyroidism (see this term), a permanent thyroid hormone deficiency that is present from birth, which results from inborn errors of thyroid hormone synthesis.	Rare genetic endocrine disease
Orphanet:95713	Athyreosis	FOXE1;NKX2-1;SLC26A4;TSHR;NKX2-5;PAX8	6	A rare form of thyroid dysgenesis characterized by complete absence of thyroid tissue that results in primary congenital hypothyroidism, a permanent thyroid deficiency that is present from birth.	Rare genetic endocrine disease
Orphanet:95712	Thyroid ectopia	NKX2-5;PAX8	2	Thyroid ectopia is a form of thyroid dysgenesis (see this term) characterized by an ectopic location of the thyroid gland that results in primary congenital hypothyroidism (see this term), a permanent thyroid deficiency that is present from birth.	Rare genetic endocrine disease
Orphanet:95699	Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency	POR	1	Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency is a unique form of congenital adrenal hyperplasia (CAH; see this term) characterized by glucocorticoid deficiency, severe sexual ambiguity in both sexes and skeletal (especially craniofacial) malformations.	Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease;Rare genetic gynecological and obstetrical diseases
Orphanet:95496	Pituitary stalk interruption syndrome	WDR11;ROBO1;PROKR2;HESX1;LHX4;CDON;GPR161	7	Pituitary stalk interruption syndrome (PSIS) is a congenital abnormality of the pituitary that is responsible for pituitary deficiency and is usually characterized by the triad of a very thin or interrupted pituitary stalk, an ectopic (or absent) posterior pituitary (EPP) and hypoplasia or aplasia of the anterior pituitary visible on MRI. In some patients the abnormality may be limited to EPP (also called ectopic neurohypophysis) or to an interrupted pituitary stalk.	Rare genetic endocrine disease
Orphanet:95494	Combined pituitary hormone deficiencies, genetic forms	POU1F1;PROP1;HESX1;OTX2;LHX4;GLI2	6	Congenital hypopituitarism is characterized by multiple pituitary hormone deficiency, including somatotroph, thyrotroph, lactotroph, corticotroph or gonadotroph deficiencies, due to mutations of pituitary transcription factors involved in pituitary ontogenesis. Congenital hypopituitarism is rare compared with the high incidence of hypopituitarism induced by pituitary adenomas, transsphenoidal surgery or radiotherapy.	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility
Orphanet:95433	Autosomal recessive spinocerebellar ataxia-blindness-deafness syndrome	PEX6;SLC52A2	2	NA	Rare genetic neurological disorder
Orphanet:95232	Lissencephaly due to LIS1 mutation	PAFAH1B1	1	Lissencephaly due to LIS1 mutation is a cerebral malformation with epilepsy characterized predominantly by posterior isolated lissencephaly with developmental delay, intellectual disability and epilepsy that usually evolves from West syndrome to Lennox-Gastaut syndrome. Additional features include muscular hypotonia, acquired microcephaly, failure to thrive and poor control of airways leading to aspiration pneumonia.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:95159	Hepatoerythropoietic porphyria	UROD	1	Hepatoerythropioetic porphyria (HEP) is a very rare form of chronic hepatic porphyria (see this term) characterized by bullous photodermatitis.	Rare genetic skin disease;Rare genetic renal disease;Rare inborn errors of metabolism
Orphanet:95428	COG8-CDG	COG8	1	The CDG (Congenital Disorders of Glycosylation) syndromes are a group of autosomal recessive disorders affecting glycoprotein synthesis. CDG syndrome type IIh is characterised by severe psychomotor retardation, failure to thrive and intolerance to wheat and dairy products.	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:94122	Cerebellar ataxia, Cayman type	ATCAY	1	A rare, autosomal recessive, congenital, cerebellar ataxia disorder characterized by hypotonia from birth, marked psychomotor delay and prominent cerebellar dysfunction (manifesting with nystagmus, intention tremor, dysarthria, ataxic gait and truncal ataxia), described in an isolated population of the Grand Cayman Island. Cerebellar hypoplasia, observed on CT scan, may be associated.	Rare genetic neurological disorder
Orphanet:94124	Spinocerebellar ataxia with axonal neuropathy type 1	TDP1	1	Spinocerebellar ataxia with axonal neuropathy type 1 is a rare, genetic neurological disorder characterized by a late childhood onset of slowly progressive cerebellar ataxia. Initial manifestations include weakness and atrophy of distal limb muscles, areflexia and loss of pain, vibration and touch sensations in upper and lower extremities. Gaze nystagmus, cerebellar dysarthria, peripheral neuropathy, stepagge gait and pes cavus develop as disease progresses. Cerebellar atrophy (especially of the vermis) is present in all affected individuals. Additional reported manifestations include seizures, mild brain atrophy, mild hypercholesterolemia and borderline hypoalbuminemia.	Rare genetic neurological disorder
Orphanet:94125	Recessive mitochondrial ataxia syndrome	POLG	1	Recessive mitochondrial ataxia syndrome is a rare, mitochondrial DNA maintenance syndrome characterized by early-onset cerebellar ataxia, and variable combination of epilepsy, headache, dysarthria, ophthalmoplegia, peripheral neuropathy, intellectual disability, psychiatric symptoms and movement disorders.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:94147	Spinocerebellar ataxia type 7	ATXN7	1	Spinocerebellar ataxia type 7 (SCA7), currently the only known form of autosomal dominant cerebellar ataxia type 2 (ADCA2; see this term), is a neurodegenerative disorder characterized by progressive ataxia, motor system abnormalities, dysarthria, dysphagia and retinal degeneration leading to progressive blindness.	Rare genetic eye disease;Rare genetic neurological disorder
Orphanet:94150	Anonychia congenita totalis	RSPO4	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic skin disease
Orphanet:94064	Deafness-infertility syndrome	CATSPER2;STRC	2	Deafness-infertility syndrome (DIS) is a very rare syndrome associating sensorineural deafness and male infertility.	Genetic otorhinolaryngologic disease;Rare chromosomal anomaly;Genetic infertility
Orphanet:94063	12q14 microdeletion syndrome	LEMD3;HMGA2	2	 gene: mutations in this gene have already been implicated in osteopoikilosis.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare chromosomal anomaly
Orphanet:94065	15q24 microdeletion syndrome	SIN3A	1	15q24 microdeletion syndrome is a rare chromosomal anomaly characterized cytogenetically by a 1.7-6.1 Mb deletion in chromosome 15q24 and clinically by pre- and post-natal growth retardation, intellectual disability, distinct facial features, and genital, skeletal, and digital anomalies.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare chromosomal anomaly
Orphanet:94068	Spondyloepiphyseal dysplasia congenita	COL2A1	1	Spondyloepiphyseal dysplasia congenita (SEDC) is a chondrodysplasia characterized by disproportionate short stature, abnormal epiphyses and flattened vertebral bodies.	Rare genetic bone disease;Rare genetic developmental defect during embryogenesis
Orphanet:94083	Partington syndrome	ARX	1	) gene (Xp22.13). Transmission is X-linked recessive.	Rare genetic neurological disorder
Orphanet:94088	Hereditary renal hypouricemia	SLC22A12;SLC2A9	2	Hereditary renal hypouricemia (HRH) is a rare autosomal recessively inherited renal membrane transport disorder affecting urate reabsorption in the proximal tubules leading to usually asymptomatic hypouricemia and predisposing to urolithiasis and exercise induced acute renal failure (EIARF).	Rare genetic renal disease
Orphanet:94089	Pseudohypoparathyroidism type 1B	GNAS;STX16	2	Pseudohypoparathyroidism type 1B (PHP-1b) is a type of pseudohypoparathyroidism (PHP; see this term) characterized by localized resistance to parathyroid hormone (PTH) mainly in the renal tissues which manifests with hypocalcemia, hyperphosphatemia and elevated PTH levels. About 60-70% of patients also present with elevated TSH levels due to TSH resistance.	Rare genetic developmental defect during embryogenesis;Rare genetic renal disease;Rare genetic endocrine disease
Orphanet:96147	Kleefstra syndrome due to 9q34 microdeletion	EHMT1	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare chromosomal anomaly
Orphanet:95720	Thyroid hypoplasia	SLC26A4;TSHR;PAX8	3	Thyroid hypoplasia is a form of thyroid dysgenesis (see this term) characterized by incomplete development of the thyroid gland that results in primary congenital hypothyroidism (see this term), a permanent thyroid deficiency that is present from birth.	Rare genetic endocrine disease
Orphanet:93552	Pediatric systemic lupus erythematosus	C1R;STAT4;SPP1;IRAK1	4	A rare, systemic, autoimmune disease characterized by inflammation in any organ system, with onset prior to adulthood, presenting highly variable clinical manifestations, which usually have a more aggressive course and higher rate of major organ involvement than adult-onset systemic lupus erythematosus, resulting in potential damage to a variety of organs (e.g. the skin, kidneys, lungs, nervous system).	
Orphanet:93562	AFib amyloidosis	FGA	1	A rare, hereditary amyloidosis with primary renal involvement characterized by fibrinogen A-alpha-chain amyloid deposition predominantly in the kidney glomeruli and clinically presenting with hypertension, uremia, nephrotic syndrome slowly progressing to end-stage renal disease. Extra-renal involvement is possible, due to neurological, cardiac, visceral and vascular amyloid deposition.	Rare genetic renal disease;Rare genetic systemic or rheumatologic disease
Orphanet:93560	AApoAI amyloidosis	APOA1	1	A rare, hereditary amyloidosis with primary renal involvement characterized by renal interstitial and medullary deposition of amyloid, low plasma levels of ApoA-1 and slow disease progression. Main clinical signs and symptoms are hypertension, proteinuria, hematuria and edema due to chronic renal insufficiency leading to end stage renal disease. Hepatosplenomegaly, progressive cardiomyopathy and involvement of skin, testes and adrenals (hypergonadotropic hypogonadism) have also been reported.	Rare genetic renal disease;Rare genetic systemic or rheumatologic disease
Orphanet:93561	ALys amyloidosis	LYZ	1	A rare, hereditary amyloidosis with primary renal involvement characterized by amyloid deposition in the kidney glomeruli and medulla, gastrointestinal tract, liver, spleen and slow disease progression. Symptoms and signs include nausea, vomiting, dyspepsia, gastritis, gastrointestinal hemorrhage, abdominal pain, hepatic rupture, sicca syndrome, purpura and petechiae, lymphadenopathy and renal dysfunction.	Rare genetic renal disease;Rare genetic systemic or rheumatologic disease
Orphanet:93571	Dense deposit disease	CFH;CFHR1	2	Dense deposit disease, a histological subtype of MPGN (see this term) is an idiopathic chronic progressive kidney disorder distinguished by the presence of intra-membranous dense deposits in addition to immune complex subendothelial deposits in the glomerular capillary walls. This form often has a higher recurrence rate after a kidney transplant and is associated with extra-renal manifestations such as familial drusen (see this term).	
Orphanet:93474	Scheie syndrome	IDUA	1	Scheie syndrome is the mildest form of mucopolysaccharidosis type 1 (MPS1; see this term), a rare lysosomal storage disease, characterized by skeletal deformities and a delay in motor development.	Rare genetic bone disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:93476	Hurler-Scheie syndrome	IDUA	1	Hurler-Scheie syndrome is the intermediate form of mucopolysaccharidosis type 1 (MPS1; see this term) between the two extremes Hurler syndrome and Scheie syndrome (see these terms); it is a rare lysosomal storage disease, characterized by skeletal deformities and a delay in motor development.	Rare genetic bone disease;Rare genetic cardiac disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:93473	Hurler syndrome	IDUA	1	Hurler syndrome is the most severe form of mucopolysaccharidosis type 1 (MPS1; see this term), a rare lysosomal storage disease, characterized by skeletal abnormalities, cognitive impairment, heart disease, respiratory problems, enlarged liver and spleen, characteristic facies and reduced life expectancy.	Rare genetic bone disease;Rare genetic cardiac disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:93399	Juvenile sialidosis type 2	NEU1	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic neurological disorder;Rare genetic renal disease;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:93400	Congenital sialidosis type 2	NEU1	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic neurological disorder;Rare genetic renal disease;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:93405	Syndactyly type 4	SHH;LMBR1	2	Syndactyly type 4 (SD4) is a very rare congenital distal limb malformation characterized by complete bilateral syndactyly (involving all digits 1 to 5).	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93404	Syndactyly type 3	GJA1	1	Syndactyly type 3 (SD3) is a rare congenital distal limb malformation characterized by complete and bilateral syndactyly between the 4th and 5th fingers.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93406	Syndactyly type 5	HOXD13	1	Syndactyly type 5 (SD5) is a very rare congenital limb malformation characterized by postaxial syndactyly of hands and feet, associated with metacarpal and metatarsal fusion of fourth and fifth digits.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93409	Brachydactyly-syndactyly, Zhao type	HOXD13	1	Brachydactyly-syndactyly, Zhao type is a recently described syndrome associating a brachydactyly type A4 (short middle phalanges of the 2nd and 5th fingers and absence of middle phalanges of the 2nd to 5th toes) and a syndactyly of the 2nd and 3rd toes. Metacarpals and metatarsals anomalies are common.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93360	Spondyloepimetaphyseal dysplasia with multiple dislocations	KIF22	1	Spondyloepimetaphyseal dysplasia with multiple dislocations is a rare genetic primary bone dysplasia disorder characterized by midface hypoplasia, short stature, generalized joint laxity, multiple joint dislocations (most frequently of knees and hips), limb malalignment (genu valgum/varum) and progressive spinal deformity (e.g. kyphosis/scoliosis). Radiography reveals distinctive slender metacarpals and metatarsals, as well as small, irregular epiphyses, metaphyseal irregularities with vertical striations, constricted femoral necks and mild platyspondyly, among others.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93359	Spondyloepimetaphyseal dysplasia with joint laxity	B3GALT6	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic skin disease;Rare genetic eye disease;Rare inborn errors of metabolism
Orphanet:93358	Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome	DDR2	1	Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome is a rare, genetic primary bone dysplasia disorder characterized by disproportionate short stature with shortening of upper and lower limbs, short and broad fingers with short hands, narrowed chest with rib abnormalities and pectus excavatum, abnormal chondral calcifications (incl. larynx, trachea and costal cartilages) and facial dysmorphism (frontal bossing, hypertelorism, prominent eyes, short flat nose, wide nostrils, high-arched palate, long philtrum). Platyspondyly (esp. of cervical spine) and abnormal epiphyses and metaphyses are observed on radiography. Atlantoaxial instability causing spinal compression and recurrent respiratory disease are potential complications that may result lethal.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93372	Familial hypocalciuric hypercalcemia type 1	CASR	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic endocrine disease
Orphanet:93383	Brachydactyly type B	ROR2	1	Brachydactyly type B (BDB) is a very rare congenital malformation characterized by hypoplasia or aplasia of the terminal parts of fingers 2 to 5, with complete absence of the fingernails.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93387	Brachydactyly type E	HOXD13;PTHLH	2	Brachydactyly type E (BDE) is a congenital malformation of the digits characterized by variable shortening of the metacarpals with more or less normal length phalanges, although the terminal phalanges are often short.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93388	Brachydactyly type A1	BMPR1B;GDF5;IHH	3	Brachydactyly type A1 (BDA1) is a congenital malformation characterized by apparent shortness (or absence) of the middle phalanges of all digits, and occasional fusion with the terminal phalanges.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93384	Brachydactyly type C	BMPR1B;GDF5	2	), have been reported in BDC patients. Many studies support an autosomal dominant mode of inheritance.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93396	Brachydactyly type A2	BMP2;GDF5;BMPR1B	3	Brachydactyly type A2 (BDA2) is a congenital malformation characterized by shortening (hypoplasia or aplasia) of the middle phalanges of the index finger and, sometimes, of the little finger.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:93974	Smith-Fineman-Myers syndrome	ATRX	1	An X-linked mental retardation (XLMR) syndrome belonging to the group of conditions characterised by the association of intellectual deficit with hypotonic facies (Mental retardation, X-linked-hypotonic facies).	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:93971	Chudley-Lowry-Hoar syndrome	ATRX	1	An X-linked mental retardation (XLMR) syndrome belonging to the group of conditions characterised by the association of intellectual deficit with hypotonic facies (Mental retardation-hypotonic facies).	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:93970	Holmes-Gang syndrome	ATRX	1	An X-linked mental retardation (XLMR) syndrome belonging to the group of conditions characterised by the association of intellectual deficit with hypotonic facies (Mental retardation, X-linked-hypotonic facies).	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:93973	Carpenter-Waziri syndrome	ATRX	1	An X-linked mental retardation (XLMR) syndrome belonging to the group of conditions characterised by the association of intellectual deficit with hypotonic facies (Mental retardation, X-linked-hypotonic facies).	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:93972	Juberg-Marsidi syndrome	ATRX	1	An X-linked mental retardation (XLMR) syndrome belonging to the group of conditions characterised by the association of intellectual deficit with hypotonic facies (Mental retardation, X-linked-hypotonic facies).	Rare genetic urogenital disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:93932	FG syndrome type 1	MED12	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:93930	Bladder exstrophy	TP63;ISL1	2	A congenital genitourinary malformation belonging to the spectrum of the exstrophy-epispadias complex (EEC) and is characterized by an evaginated bladder plate, epispadias and an anterior defect of the pelvis, pelvic floor and abdominal wall.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis
Orphanet:93926	Midline interhemispheric variant of holoprosencephaly	PTCH1;SHH;SIX3;TGIF1;ZIC2;GLI2;TDGF1;FOXH1;FGF8;DISP1;CDON;NODAL;DLL1;GAS1	14	Midline interhemispheric variant of holoprosencephaly (MIH) or syntelencephaly is a form of holoprosencephaly (HPE; see this term) characterized by non-separation of the posterior frontal and parietal lobes, normally-formed callosal genu and splenium, absence of the callosal body, normally-separated hypothalamus and lentiform nucleus, and frequent heterotopic gray matter.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease
Orphanet:93924	Lobar holoprosencephaly	FGFR1;PTCH1;SHH;SIX3;TGIF1;ZIC2;GLI2;TDGF1;FOXH1;FGF8;DISP1;CDON;NODAL;DLL1;GAS1	15	Lobar holoprosencephaly is the mildest classical form of holoprosencephaly (HPE; see this term) characterized by separation of the right and left cerebral hemispheres and lateral ventricules with some continuity across the frontal neocortex, especially rostrally and ventrally.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease
Orphanet:93925	Alobar holoprosencephaly	PTCH1;SHH;SIX3;TGIF1;ZIC2;GLI2;TDGF1;FOXH1;FGF8;DISP1;CDON;NODAL;DLL1;GAS1	14	A disorder of the most severe classical form of holoprosencephaly (HPE) characterized by a single brain ventricle and no interhemispheric fissure.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare genetic endocrine disease
Orphanet:93921	Schwannomatosis	NF2;SMARCB1;COQ6;LZTR1	4	Neurofibromatosis (NF) type 3 (NF3), also known as schwannomatosis, is the least frequent form of the rare genetic disorder neurofibromatosis. It is clinically and genetically distinct from NF1 and NF2 and is characterized by the development of multiple schwannomas (nerve sheath tumors), without involvement of the vestibular nerves. NF3 develops in adulthood and is often associated with chronic pain. Dysesthesia and paresthesia may also be present. Common localizations include the spine, peripheral nerves, and the cranium.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis
Orphanet:93952	X-linked intellectual disability, Hedera type	ATP6AP2	1	X-linked intellectual disability, Hedera type is a rare X-linked intellectual disability syndrome characterized by an onset in infancy of delayed motor and speech milestones, generalized tonic-clonic seizures and drop attacks, and mild to moderate intellectual disability. Additional, less common manifestations include scoliosis, ataxia (resulting in progressive gait disturbance), and bilateral pes planovalgus. Physical appearance is normal with no dysmorphic features reported.	Rare genetic neurological disorder
Orphanet:93950	X-linked intellectual disability, Sutherland-Haan type	PQBP1	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:93947	X-linked intellectual disability, Golabi-Ito-Hall type	PQBP1	1	An X-linked intellectual disability syndrome (XLMR) characterized by intellectual deficiency, microcephaly and short stature. It belongs to the group of disorders collectively referred to as Renpenning syndrome.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:93946	Hamel cerebro-palato-cardiac syndrome	PQBP1	1	An X-linked intellectual disability syndrome (XLMR) characterized by intellectual deficiency, microcephaly and short stature. It belongs to the group of disorders collectively referred to as Renpenning syndrome.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:93945	X-linked intellectual disability, Porteous type	PQBP1	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:93616	Hemoglobin H disease	HBA2;HBA1	2	Hemoglobin H (HbH) disease is a moderate to severe form of alpha-thalassemia (see this term) characterized by pronounced microcytic hypochromic hemolytic anemia.	Rare genetic hematologic disease;Rare genetic endocrine disease;Rare genetic renal disease
Orphanet:93622	Dent disease type 1	CLCN5	1	Dent disease type 1 is a type of Dent disease with predominantly renal manifestations.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic endocrine disease
Orphanet:93623	Dent disease type 2	OCRL	1	Dent disease type 2 is a type of Dent disease in which patients have the manifestations of Dent disease type 1 associated with extra-renal features.	Rare genetic renal disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic endocrine disease
Orphanet:93591	Infantile nephronophthisis	NPHP3;INVS;NEK8;TTC21B;ANKS6;CEP83;ZNF423	7	NA	Rare genetic renal disease;Ciliopathy
Orphanet:93592	Juvenile nephronophthisis	NPHP1;NPHP4;GLIS2;WDR19;ANKS6;MAPKBP1	6	NA	Rare genetic renal disease;Ciliopathy
Orphanet:93589	Late-onset nephronophthisis	NPHP3;XPNPEP3;MAPKBP1	3	NA	Rare genetic renal disease;Ciliopathy
Orphanet:93598	Primary hyperoxaluria type 1	AGXT	1	Primary hyperoxaluria type 1 (PH1) is a rare disorder of glyoxylate metabolism characterized by the accumulation of oxalate due to a deficiency of the peroxisomal hepatic enzyme L-alanine: glyoxylate aminotransferase (AGT). Clinical presentation is variable, ranging from occasional symptomatic nephrolithiasis to nephrocalcinosis and end-stage renal disease with systemic involvement.	Rare genetic eye disease;Rare inborn errors of metabolism;Rare genetic renal disease
Orphanet:93578	OBSOLETE: Atypical hemolytic uremic syndrome with B factor anomaly	CFB	1	NA	NA
Orphanet:93579	OBSOLETE: Atypical hemolytic uremic syndrome with H factor anomaly	CFH	1	NA	NA
Orphanet:93575	OBSOLETE: Atypical hemolytic uremic syndrome with C3 anomaly	C3	1	NA	NA
Orphanet:93576	OBSOLETE: Atypical hemolytic uremic syndrome with MCP/CD46 anomaly	CD46	1	NA	NA
Orphanet:93583	Congenital thrombotic thrombocytopenic purpura	ADAMTS13	1	Congenital thrombotic thrombocytopenic purpura is the hereditary form of thrombotic thrombocytopenic purpura (TTP; see this term) characterized by profound peripheral thrombocytopenia, microangiopathic hemolytic anemia (MAHA) and single or multiple organ failure of variable severity.	Rare genetic hematologic disease;Rare genetic renal disease
Orphanet:93580	OBSOLETE: Atypical hemolytic uremic syndrome with I factor anomaly	CFI	1	NA	NA
Orphanet:93581	Atypical hemolytic uremic syndrome with anti-factor H antibodies	CFHR4;CFHR1;CFHR3;CFHR5	4	NA	Rare genetic hematologic disease;Rare genetic renal disease
Orphanet:93610	Distal renal tubular acidosis with anemia	SLC4A1	1	Distal renal tubular acidosis (dRTA) with anemia is a very rare form of distal renal tubular acidosis (dRTA; see this term) characterized by a defect in renal acidification and hereditary hemolytic anemia.	Rare genetic hematologic disease;Rare genetic renal disease
Orphanet:93608	Autosomal dominant distal renal tubular acidosis	SLC4A1	1	A rare inherited form of distal renal tubular acidosis (dRTA) characterized by hyperchloremic metabolic acidosis often but not always associated with hypokalemia.	Rare genetic renal disease
Orphanet:93607	Autosomal recessive proximal renal tubular acidosis	SLC4A4	1	Autosomal recessive proximal renal tubular acidosis (AR pRTA) is a rare form of proximal renal tubular acidosis (pRTA; see this term) characterized by an isolated defect in the proximal tubule leading to the decreased reabsorption of bicarbonate and consequentially to urinary bicarbonate wastage along with additional characteristic clinical features.	Rare genetic renal disease
Orphanet:93613	Cystinuria type B	SLC7A9	1	NA	Rare inborn errors of metabolism;Rare genetic renal disease
Orphanet:93612	Cystinuria type A	SLC3A1	1	NA	Rare inborn errors of metabolism;Rare genetic renal disease
Orphanet:93602	Xanthinuria type II	MOCOS	1	Type II xanthinuria, a type of classical xanthinuria (see this term), is a rare autosomal recessive disorder of purine metabolism (see this term) characterized by the deficiency of both xanthine dehydrogenase and aldehyde oxidase, leading to the formation of urinary xanthine urolithiasis and leading, in some patients, to kidney failure. Other less common manifestations include arthropathy, myopathy and duodenal ulcer, while some patients remain asymptomatic.	Rare inborn errors of metabolism;Rare genetic renal disease
Orphanet:93601	Xanthinuria type I	XDH	1	Type I xanthinuria, a type of classical xanthinuria (see this term), is a rare autosomal recessive disorder of purine metabolism (see this term) characterized by the isolated deficiency of xanthine dehydrogenase, causing hyperxanthinemia with low or absent uric acid and xanthinuria, leading to urolithiasis, hematuria, renal colic and urinary tract infections, while some patients are asymptomatic and others suffer from kidney failure. Less common manifestations include arthropathy, myopathy and duodenal ulcer.	Rare inborn errors of metabolism;Rare genetic renal disease
Orphanet:93600	Primary hyperoxaluria type 3	HOGA1	1	Primary hyperoxaluria type 3 (PH3) is a disorder of glyoxylate metabolism that can be asymptomatic or characterized by oxalate nephrolithiasis.	Rare genetic renal disease;Rare inborn errors of metabolism
Orphanet:93599	Primary hyperoxaluria type 2	GRHPR	1	Primary hyperoxaluria (PH) type 2 is a rare disorder of glyoxylate metabolism caused by the deficiency of the enzyme glyoxylate reductase/hydropyruvate reductase (GR/HPR) characterized by a childhood onset with clinical manifestations that include recurrent nephrolithiasis, nephrocalcinosis and end-stage renal disease with subsequent systemic oxalosis.	Rare genetic renal disease;Rare inborn errors of metabolism
Orphanet:93606	Nephrogenic syndrome of inappropriate antidiuresis	AVPR2	1	Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a rare genetic disorder of water balance, closely resembling the far more frequent syndrome of inappropriate antidiuretic secretion (SIAD), and characterized by euvolemic hypotonic hyponatremia due to impaired free water excretion and undetectable or low plasma arginine vasopressin (AVP) levels.	Rare genetic renal disease
Orphanet:93605	Classic Bartter syndrome	CLCNKB	1	Classic Bartter syndrome is a type of Bartter syndrome (see this term), characterized by a milder clinical picture than the antenatal/infantile subtype, and presenting with failure to thrive, hypokalemic alkalosis, increased levels of plasma renin and aldosterone, low blood pressure and vascular resistance to angiotensin II.	Rare genetic renal disease
Orphanet:93604	Antenatal Bartter syndrome	SLC12A1;KCNJ1;MAGED2	3	A phenotypic variant of Bartter syndrome presenting antenatally with maternal polyhydramnios, pre-term delivery and postnatally with polyuria, and nephrocalcinosis. Hypokalemic alkalosis, increased levels of plasma renin and aldosterone, low blood pressure and vascular resistance to angiotensin II are characteristically associated. Genotypically they comprise Type 1 and Type 2 Bartter syndrome	Rare genetic renal disease
Orphanet:99068	Complete atrioventricular canal-tetralogy of Fallot syndrome	NR2F2;GATA4;CRELD1	3	NA	Rare genetic developmental defect during embryogenesis
Orphanet:99067	Complete atrioventricular canal-ventricle hypoplasia syndrome	NR2F2;CRELD1;GATA6;GATA4	4	NA	Rare genetic developmental defect during embryogenesis
Orphanet:99066	Complete atrioventricular canal-left heart obstruction syndrome	CRELD1;GATA4;NR2F2	3	NA	Rare genetic developmental defect during embryogenesis
Orphanet:99106	Atrial septal defect, ostium primum type	TLL1	1	NA	Rare genetic developmental defect during embryogenesis
Orphanet:99105	Atrial septal defect, sinus venosus type	CITED2	1	NA	Rare genetic developmental defect during embryogenesis
Orphanet:99103	Atrial septal defect, ostium secundum type	ACTC1;GATA4;MYH6;NKX2-5;TBX20;TBX20;TLL1;CITED2;GATA6	9	NA	Rare genetic developmental defect during embryogenesis
Orphanet:99141	Lymphedema-posterior choanal atresia syndrome	PTPN14	1	NA	Rare genetic developmental defect during embryogenesis;Genetic otorhinolaryngologic disease
Orphanet:99361	Familial medullary thyroid carcinoma	ESR2;RET;NTRK1	3	NA	Inherited cancer-predisposing syndrome;Rare genetic endocrine disease;Rare genetic tumor
Orphanet:99657	Primary dystonia, DYT2 type	HPCA	1	Primary dystonia DYT2 type is characterized by segmental dystonia that manifests with involuntary posturing affecting predominantly the feet.	Rare genetic neurological disorder
Orphanet:99429	Complete androgen insensitivity syndrome	AR	1	Complete androgen insensitivity syndrome (CAIS) is a form of androgen insensitivity syndrome (AIS; see this term), a disorder of sex development (DSD), characterized by the presence of female external genitalia in a 46,XY individual with normal testis development but undescended testes and unresponsiveness to age-appropriate levels of androgens.	Rare genetic gynecological and obstetrical diseases;Genetic infertility;Rare genetic developmental defect during embryogenesis;Rare genetic urogenital disease;Rare genetic endocrine disease
Orphanet:99646	Metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria	IDH1	1	Metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria is an extremely rare genetic disorder characterized by the unique association of enchondromatosis with D-2 hydroxyglutaric aciduria (see these terms). Clinical features include enchondromatosis (with short stature, severe metaphyseal dysplasia and mild vertebral involvement), elevated levels of urinary 2-hydroxyglutaric acid and mild developmental delay.	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:99718	Leber plus disease	MT-ND4;MT-ND6;MT-ND3	3	Leber `plus' disease describes patients with the clinical features of Leber's hereditary optic neuropathy (LHON; see term) in combination with other serious systemic or neurological abnormalities. These abnormalities include: postural tremor, motor disorder, multiple sclerosis-like syndrome, spinal cord disease, skeletal changes, Parkinsonism with dystonia, anarthria, dystonia, motor and sensory peripheral neuropathy, spasticity and mild encephalopathy. It is caused by maternally-inherited mitochondrial DNA (mtDNA) mutations.	Rare genetic cardiac disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:99749	Kostmann syndrome	HAX1	1	Kostmann syndrome is a rare, severe, congenital neutropenia disorder characterized by a lack of mature neutrophils (absolute neutrophil counts less than 500 cells/mm3) associated with frequent, recurrent bacterial infections (e.g. otitis media, pneumonia, sinusitis, urinary tract infections, abscesses of skin and/or liver) and increased promyelocytes in the bone marrow. Periodontal disease, as well as neurological symptoms, such as cognitive impairment, severe neurodegeneration and epilepsy, have been reported in some patients.	Rare genetic immune disease
Orphanet:99757	Embryonal rhabdomyosarcoma	SLC22A18	1	NA	
Orphanet:99756	Alveolar rhabdomyosarcoma	FOXO1;PAX3;PAX7	3	NA	
Orphanet:99734	Myotonia fluctuans	SCN4A	1	Myotonia fluctuans (MF) is a form of potassium-aggravated myotonia (PAM, see this term) which is cold insensitive, dramatically fluctuating and profoundly worsened by potassium ingestion.	Rare genetic neurological disorder
Orphanet:99731	Isolated sulfite oxidase deficiency	SUOX	1	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic eye disease
Orphanet:99735	Myotonia permanens	SCN4A	1	Myotonia permanens is a very rare, persistent and more severe form of potassium-aggravated myotonia (PAM, see this term).	Rare genetic neurological disorder
Orphanet:99736	Acetazolamide-responsive myotonia	SCN4A	1	A form of potassium-aggravated myotonia (PAM) which shows dramatic improvement with the use of acetazolamide (ACZ).	Rare genetic neurological disorder
Orphanet:99741	King-Denborough syndrome	RYR1	1	King-Denborough syndrome is a rare genetic non-dystrophic myopathy characterized by the triad of congenital myopathy, dysmorphic features and susceptibility to malignant hyperthermia. Patients present with a wide phenotypic range, including delayed motor development, muscle weakness and fatigability, ptosis and facies myopathica (with or without creatine kinase elevations), skeletal abnormalities (e.g. short stature, scoliosis, kyphosis, lumbar lordosis and pectus carinatum/excavatum), mild dysmorphic facial features (e.g. hypertelorism, down-slanting palpebral fissures, epicanthic folds, low set ears, micrognathia), webbing of the neck, cryptorchidism, and a susceptibility to malignant hyperthermia and/or rhabdomyolysis due to intensive physical strain, viral infection or statin use.	Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:99742	Amish lethal microcephaly	SLC25A19	1	A very rare syndrome characterized by extreme microcephaly and early death, within the first year.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:98820	Familial focal epilepsy with variable foci	DEPDC5;NPRL2;NPRL3	3	Familial focal epilepsy with variable foci is a rare genetic epilepsy disorder characterized by autosomal dominant lesional and nonlesional focal epilepsy with variable penetrance. Focal seizures emanate from different cortical locations (temporal, frontal, centroparietal, parietal, parietaloccipital, occipital) in different family members, but for each individual a single focus remains constant throughout lifetime. Seizure type (tonic, tonic-clonic or hyperkinetic) and severity varies among family members and tends to decrease (but do not disappear) during adulthood. Many patients have an aura and show automatisms during diurnal seizures whereas others have nocturnal seizures. Most individuals are of normal intelligence but patients with intellectual disability, autistic spectrum disorder and obsessive-compulsive disorder have been described.	Rare genetic neurological disorder
Orphanet:98818	Landau-Kleffner syndrome	GRIN2A	1	Landau-Kleffner syndrome (LKS) is an age-related epileptic encephalopathy where developmental regression occurs mainly in the language domain and the electroencephalographic (EEG) abnormalities are mainly localized around the temporal-parietal regions. The term acquired epileptic aphasia describes the main features of this condition.	Rare genetic neurological disorder
Orphanet:98813	Hypohidrotic ectodermal dysplasia with immunodeficiency	IKBKG;NFKBIA	2	Hypohidrotic ectodermal dysplasia with immunodeficiency (HED-ID) is a type of HED (see this term) characterized by the malformation of ectodermal structures such as skin, hair, teeth and sweat glands, and associated with immunodeficiency.	Rare genetic skin disease;Rare genetic developmental defect during embryogenesis;Rare genetic immune disease;Rare genetic eye disease
Orphanet:98811	Paroxysmal exertion-induced dyskinesia	SLC2A1;PRRT2	2	Paroxysmal exertion-induced dyskinesia (PED) is a form of paroxysmal dyskinesia (see this term), characterized by painless attacks of dystonia of the extremities triggered by prolonged physical activities.	Rare genetic neurological disorder
Orphanet:98810	Paroxysmal non-kinesigenic dyskinesia	PNKD;PRRT2	2	Paroxysmal non-kinesigenic dyskinesia (PNKD) is a form of paroxysmal dyskinesia (see this term), characterized by attacks of dystonic or choreathetotic movements precipitated by stress, fatigue, coffee or alcohol intake or menstruation.	Rare genetic neurological disorder
Orphanet:98809	Paroxysmal kinesigenic dyskinesia	PRRT2;KCNA1	2	Paroxysmal kinesigenic dyskinesia (PKD) is a form of paroxysmal dyskinesia (see this term), characterized by recurrent brief involuntary hyperkinesias, such as choreoathetosis, ballism, athetosis or dystonia, triggered by sudden movements.	Rare genetic neurological disorder
Orphanet:98808	Autosomal dominant dopa-responsive dystonia	GCH1	1	A rare neurometabolic disorder characterized by childhood-onset dystonia that shows a dramatic and sustained response to low doses of levodopa (L-dopa) and that may be associated with parkinsonism at an older age.	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:98807	Primary dystonia, DYT13 type	DYT13	1	DYT13 type primary dystonia is characterized by focal or segmental dystonia with cranial, cervical, or upper limb involvement.	Rare genetic neurological disorder
Orphanet:98837	Acute biphenotypic leukemia	KMT2A;FLT3	2	NA	NA
Orphanet:98838	Primary mediastinal large B-cell lymphoma	BCL6;XPO1	2	Primary mediastinal B-cell lymphoma (PMBL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL; see this term), arising from B cells of thymic origin, that affects mainly women between the ages of 20-30, that usually presents with a bulky and rapidly expanding anterior mediastinal mass, often with pleural and pericardial effusions, and that can invade the lungs, superior vena cava, pleura, pericardium, and chest wall, leading to manifestations of cough, dyspnea, and superior vena cava syndrome.	
Orphanet:98835	Acute undifferentiated leukemia	KMT2A	1	A rare acute leukemia of ambiguous lineage characterized by clonal proliferation of primitive hematopoietic cells, primarily in the bone marrow and blood, lacking lineage-specific markers and detectable genotypic alterations. The patients present with leukocytosis, anemia, variable platelet count and a variety of nonspecific symptoms related to ineffective hematopoesis (fatigue, bleeding and bruising, recurrent infections, bone pain) and/or extramedullary site involvement (lymphadenopathy, splenomegaly, hepatomegaly).	
Orphanet:98836	Bilineal acute leukemia	KMT2A	1	NA	NA
Orphanet:98833	Acute myeloblastic leukemia without maturation	FLT3;NPM1	2	A rare, acute myeloid leukemia characterized by no significant myeloid maturation and more than 90% blast cells in the non-erythroid population. Various degrees of anemia, thrombocytopenia, or pancytopenia are present. Frequent clinical manifestations include fatigue, fever, bleeding disorders, and organomegaly, especially hepatosplenomegaly.	
Orphanet:98834	Acute myeloblastic leukemia with maturation	FLT3;KIT;NPM1	3	A rare, acute myeloid leukemia characterized by evidence of granulocytic maturation and more than 20% of blast cells in the bone marrow and/or peripheral blood. The maturing non-blast granulocytic cells account for greater than or equal to 10% and monocytic cells less than or equal to 20% of the bone marrow cells. Various degrees of anemia, thrombocytopenia, or pancytopenia are present. Frequent clinical manifestations include fatigue, fever, bleeding disorders, and organomegaly, especially hepatosplenomegaly.	
Orphanet:98831	Acute myeloid leukemia with 11q23 abnormalities	KMT2A	1	A rare tumor arising from hematopoietic and lymphoid tissues characterized by abnormal proliferation and differentiation of a clonal population of myeloid stem cells carrying unspecific 11q23 abnormalities. Clinical manifestations result from accumulation of malignant myeloid cells within the bone marrow, peripheral blood and other organs, and include leukocytosis, anemia, thrombocytopenia, fatigue, anorexia and weight loss.	
Orphanet:98832	Acute myeloid leukemia with minimal differentiation	FLT3	1	A rare subtype of acute myeloid leukemia characterized by clonal proliferation of poorly differentiated myeloid blasts in the bone marrow, blood or other tissues. It usually presents with anemia, thrombocytopenia and other nonspecific symptoms related to ineffective hematopoesis (fatigue, bleeding and bruising, recurrent infections, bone pain) and/or extramedullary site involvement (gingivitis, splenomegaly). Low remission rates are reported.	
Orphanet:98829	Acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22)	FLT3;MYH11;CBFB;KIT	4	A rare acute myeloid leukemia (AML) with recurrent genetic anomaly disorder characterized by an inv(16)(p13q22) or t(16;16)(p13;q22) cytogenic abnormality, which generates a CBFB-MYH11 fusion gene, presenting with typical morphologic features of AML as well as abnormal bone marrow eosinophils (seen in all stages of maturation with no significant signs of maturation arrest). Myeloid sarcoma and involvement of the central nervous system is relatively common. Cytology reveals myeloblasts, a significant monocytic component and variable numbers of immature eosinophils with atypical purple-violet granules in addition to eosinophilic granules. Presence of the fusion gene is sufficent for diagnosis irrespective of blast count.	
Orphanet:98826	Refractory anemia	TET2	1	Refractory cytopenias with unilineage dysplasia (RCUD) is a frequent low-risk subtype of myelodysplastic syndrome (MDS; see this term) characterized by refractory cytopenias associated with dysplasia limited to one cell lineage.	
Orphanet:98823	Chronic myelomonocytic leukemia	PDGFRB;ETV6	2	NA	
Orphanet:98824	Atypical chronic myeloid leukemia	CSF3R	1	NA	
Orphanet:98853	Autosomal dominant Emery-Dreifuss muscular dystrophy	LMNA;SYNE1;TMEM43;SYNE2	4	NA	Rare genetic cardiac disease;Rare genetic neurological disorder;Laminopathy
Orphanet:98849	Systemic mastocytosis with associated hematologic neoplasm	KIT	1	An advanced form of systemic mastocytosis (SM) characterized by the abnormal accumulation of neoplastic mast cells (MCs) in one or more extracutaneous organs, mainly the bone marrow, associated with another hematologic neoplasm of non MC nature.	
Orphanet:98843	Classic Hodgkin lymphoma, nodular sclerosis type	KLHDC8B	1	NA	
Orphanet:98839	Intravascular large B-cell lymphoma	BCL6;BCL2	2	Intravascular large B-cell lymphoma (IVLBCL) is a very rare form of diffuse large B-cell lymphoma (see this term) characterized by the selective growth of lymphoma cells within the lumina of small blood vessels (especially the capillaries) that most often presents with a wide range of clinical manifestations (as potentially any tissue can be involved), with patients from Western countries more frequently manifesting with neurological and cutaneous symptoms while patients from Asian countries more frequently displaying hepatosplenomegaly and thrombocytopenia. IVLBCL is characterized by an absence of lymphadenopathy, an aggressive clinical course and a poor prognosis.	
Orphanet:98842	Lymphomatoid papulosis	TYK2;NPM1	2	Lymphomatoid papulosis (LyP) is a rare cutaneous condition characterized by chronic, recurrent, and self-regressing papulonodular skin eruptions. It belongs to the spectrum of primary cutaneous CD30+ lymphoproliferative disorders, along with primary cutaneous anaplastic large cell lymphoma (primary C-ALCL; see this term) with which it shares overlapping clinical and histopathologic features.	
Orphanet:98868	Southeast Asian ovalocytosis	SLC4A1	1	Southeast Asian ovalocytosis (SAO) is a rare hereditary red cell membrane defect characterized by the presence of oval-shaped erythrocytes and with most patients being asymptomatic or occasionally manifesting with mild symptoms such as pallor, jaundice, anemia and gallstones.	Rare genetic hematologic disease
Orphanet:98869	Congenital dyserythropoietic anemia type I	CDAN1;C15ORF41	2	Congenital dyserythropoietic anemiatype I (CDA I) is a hematologic disorder of erythropoiesis characterized by moderate to severe macrocytic anemia occasionally associated with limb or nail deformities and scoliosis.	Rare genetic hematologic disease
Orphanet:98870	Congenital dyserythropoietic anemia type III	KIF23	1	Congenital dyserythropoietic anemia type III (CDA III) is a rare form of CDA (see this term) characterized by dyserythropoiesis, with big multinucleated erythroblasts in the bone marrow, and manifesting with mild to moderate anemia.	Rare genetic hematologic disease
Orphanet:98863	X-linked Emery-Dreifuss muscular dystrophy	EMD;FHL1	2	NA	Rare genetic cardiac disease;Rare genetic neurological disorder
Orphanet:98855	Autosomal recessive Emery-Dreifuss muscular dystrophy	LMNA	1	NA	Rare genetic cardiac disease;Rare genetic neurological disorder;Laminopathy
Orphanet:98856	Charcot-Marie-Tooth disease type 2B1	LMNA	1	Charcot-Marie-Tooth disease, type 2B1 (CMT2B1, also referred to as CMT4C1) is an axonal CMT peripheral sensorimotor polyneuropathy.	Rare genetic neurological disorder;Laminopathy
Orphanet:98881	Familial dysfibrinogenemia	FGA;FGB;FGG	3	Familial dysfibrinogenemia is a coagulation disorder characterized by a bleeding tendency due to a functional anomaly of circulating fibrinogen.	Rare genetic hematologic disease
Orphanet:98880	Familial afibrinogenemia	FGA;FGB;FGG	3	Familial afibrinogenemia is a coagulation disorder characterized by bleeding symptoms due to a complete absence of circulating fibrinogen.	Rare genetic hematologic disease
Orphanet:98885	Bleeding diathesis due to glycoprotein VI deficiency	GP6	1	NA	Rare genetic hematologic disease
Orphanet:98873	Congenital dyserythropoietic anemia type II	SEC23B	1	Congenital dyserythropoietic anemia type II (CDA II) is the most common form of CDA (see this term) characterized by anemia, jaundice and splenomegaly and often leading to liver iron overload and gallstones.	Rare inborn errors of metabolism;Rare genetic hematologic disease
Orphanet:98895	Becker muscular dystrophy	DMD	1	Becker muscular dystrophy (BMD) is a neuromuscular disease characterized by progressive muscle wasting and weakness due to degeneration of skeletal, smooth and cardiac muscle.	Rare genetic neurological disorder;Rare genetic cardiac disease
Orphanet:98896	Duchenne muscular dystrophy	DMD;LTBP4	2	Duchenne muscular dystrophy (DMD) is a neuromuscular disease characterized by rapidly progressive muscle weakness and wasting due to degeneration of skeletal, smooth and cardiac muscle.	Rare genetic neurological disorder;Rare genetic eye disease;Rare genetic cardiac disease
Orphanet:98902	Amish nemaline myopathy	TNNT1	1	A type of nemaline myopathy (NM) only observed in several families of the Amish community.	Rare genetic neurological disorder
Orphanet:98889	Bilateral perisylvian polymicrogyria	SRPX2;ADGRG1;PI4KA	3	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:98890	Early-onset X-linked optic atrophy	OPA2	1	Early-onset X-linked optic atrophy is a rare form of hereditary optic atrophy, seen in only 4 families to date, with an onset in early childhood, characterized by progressive loss of visual acuity, significant optic nerve pallor and occasionally additional neurological manifestations, with females being unaffected.	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:98892	Periventricular nodular heterotopia	ARFGEF2;FLNA;ERMARD;NEDD4L;TMTC3;MAP1B	6	Periventricular nodular heterotopia (PNH) is a brain malformation, due to abnormal neuronal migration, in which a subset of neurons fails to migrate into the developing cerebral cortex and remains as nodules that line the ventricular surface. Classical PNH is a rare X-linked dominant disorder far more frequent in females who present normal intelligence to borderline intellectual deficit, epilepsy of variable severity and extra-central nervous system signs, especially cardiovascular defects or coagulopathy. The disorder is generally associated with prenatal lethality in males.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:98912	Late-onset distal myopathy, Markesbery-Griggs type	LDB3	1	A rare, genetic, non-dystrophic myofibrillar myopathy disorder characterized by late-adult onset of distal and/or proximal limb muscle weakness with initial involvement of posterior lower leg muscles, medial gastrocnemius and soleus. Patients present with ankle weakness followed by weakness of finger and wrist extensors and later on of proximal muscles. Ambulation is usually preserved. Late-onset associated cardiomyopathy and/or neuropathy has been reported in a minority of cases.	Rare genetic neurological disorder
Orphanet:98911	Distal myotilinopathy	MYOT	1	A rare, late adult-onset myofibrillar myopathy characterized by progressive distal muscle weakness associated with peripheral neuropathy and hyporeflexia. Ambulation may be lost within a few years.	Rare genetic neurological disorder
Orphanet:98914	Presynaptic congenital myasthenic syndromes	CHAT;AGRN;SLC25A1;SNAP25;SYT2;MYO9A;SLC5A7;VAMP1;SLC18A3;COL13A1	10	NA	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:98913	Postsynaptic congenital myasthenic syndromes	RAPSN;SCN4A;CHRNA1;CHRNA1;CHRNB1;CHRNB1;CHRND;CHRND;CHRNE;CHRNE;DOK7;MUSK;LRP4;AGRN;AK9;COL13A1	16	NA	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:98916	Acute inflammatory demyelinating polyradiculoneuropathy	PMP22	1	A rare inflammatory neuropathy belonging to the clinical spectrum of Guillain-Barré syndrome (GBS).	
Orphanet:98915	Synaptic congenital myasthenic syndromes	COLQ;LAMB2	2	NA	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:98904	Congenital myopathy with excess of thin filaments	ACTA1	1	A rare, genetic, congenital myopathy disorder characterized by variable degrees of muscular weakness, frequently associated with severe nemaline myopathy-like disease (including neonatal hypotonia, lack of spontaneous movements, feeding and swallowing difficulties, frequent respiratory infections, respiratory insufficiency, early death), and histopathologic findings of large, densely packed, subsarcolemmal accumulations of thin, actin-immunopositive filaments (with or without intranuclear nemaline rods) on muscle biopsy.	Rare genetic neurological disorder
Orphanet:98905	Congenital multicore myopathy with external ophthalmoplegia	RYR1	1	NA	Rare genetic neurological disorder
Orphanet:98908	Neutral lipid storage myopathy	PNPLA2	1	NA	Rare genetic neurological disorder;Rare inborn errors of metabolism
Orphanet:98907	Neutral lipid storage disease with ichthyosis	ABHD5	1	NA	Rare genetic neurological disorder;Rare inborn errors of metabolism;Rare genetic eye disease;Rare genetic skin disease
Orphanet:98909	Desminopathy	DES	1	A rare genetic skeletal muscle disease characterized by abnormal chimeric aggregates of desmin and other cytoskeletal proteins and granulofilamentous material at the ultrastructural level in muscle biopsies and variable clinical myopathological features, age of disease onset and rate of disease progression. Patients present with bilateral skeletal muscle weakness that starts in distal leg muscles and spreads proximally, sometimes involving trunk, neck flexors and facial muscles and often cardiomyopathy manifested by conduction blocks, arrhythmias, chronic heart failure, and sometimes tachyarrhythmia. Weakness eventually leads to wheelchair dependence. Respiratory insufficiency can be a major cause of disability and death, beginning with nocturnal hypoventilation with oxygen desaturation and progressing to daytime respiratory failure.	Rare genetic cardiac disease;Rare genetic neurological disorder
Orphanet:98933	Multiple system atrophy, parkinsonian type	COQ2	1	Multiple system atrophy, parkinsonian type (MSA-p) is a form of multiple system atrophy (MSA; see this term) with predominant parkinsonian features (bradykinesia, rigidity, irregular jerky postural tremor, and postural instability).	
Orphanet:98934	Huntington disease-like 2	JPH3	1	Huntington disease-like 2 (HDL2) is a severe neurodegenerative disorder considered part of the neuroacanthocytosis syndromes (see this term) characterized by a triad of movement, psychiatric, and cognitive abnormalities.	Rare genetic neurological disorder
Orphanet:98920	Spinal muscular atrophy with respiratory distress type 1	IGHMBP2	1	Spinal muscular atrophy with respiratory distress type 1 is a rare genetic motor neuron disease characterized by severe respiratory distress/respiratory failure in association with diaphragmatic eventration and palsy, as well as progressive, symmetrical, distal-to-proximal muscle weakness and atrophy (in lower limbs especially). Patients typically have a history of intrauterine growth retardation, low birth weight, feeble cry, weak suck and failure to thrive and present with inspiratory stridor, recurrent episodes of dyspnea or apnea, cyanosis and absent deep tendon reflexes. Kyphosis/scoliosis, foot deformities and joint contractures are frequently associated features.	Rare genetic neurological disorder
Orphanet:98942	Coloboma of choroid and retina	ACTG1;FZD5;SALL2;ABCB6;PAX6	5	Coloboma of choroid and retina is a rare, genetic developmental defect during embryogenesis characterized by the partial absence of retinal pigment epithelium and choroid, most frequently located in the inferonasal quadrant. Patients usually present reduced vision and have an increased risk for retinal detachment. Other ocular anomalies (e.g. coloboma of iris, microcornea, nystagmus, strabismus, microphthalmos) are usually associated, however it may also be isolated.	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:98938	Colobomatous microphthalmia	SHH;STRA6;VSX2;GDF6;GDF3;ABCB6;TENM3;RBP4	8	Colobomatous microphthalmia is a developmental disorder of the eye characterized by unilateral or bilateral microphthalmia associated with ocular coloboma.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:98949	Complete cryptophthalmia	FREM2	1	NA	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:98947	Coloboma of optic disc	FZD5;SALL2;ABCB6;PAX6	4	Coloboma of optic disc is a rare, genetic, developmental defect of the eye characterized by a unilateral or bilateral, sharply demarcated, bowl-shaped, glistening white excavation on the optic disc (typically decentered inferiorly) which usually manifests with varying degrees of reduced visual acuity. It can occur isolated or may associate other ocular (e.g. retinal detachment, retinoschisis-like separation) or systemic anomalies (e.g. renal).	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:98945	Coloboma of macula	FZD5;SALL2;ABCB6;PAX6	4	Coloboma of macula is a rare, non-syndromic developmental defect of the eye characterized by well-circumscribed, oval or rounded, usually unilateral, atrophic lesions of varying size presenting rudimentary or absent retina, choroid and sclera located at the macula leading to decreased vision and, on occasion, other symptoms (e.g. strabismus). It is usually isolated, but may also be associated with Down syndrome, skeletal or renal disorders.	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:98946	Coloboma of eyelid	FZD5;SALL2;ABCB6;PAX6	4	A rare, genetic, developmental defect of the eye characterized by a uni- or bilateral, symmetrical or asymmetrical, partial or full thickness defect of the superior or inferior eyelid margin, ranging in size from a small notch to complete absence of the entire lid, typically located on the medial to lateral third of the eyelid, resulting in an unprotected cornea and thus possibly leading to exposure keratopathy and vision impairment. It may occur isolated, be associated with other ocular defects or be part of a craniofacial syndrome, such as Treacher-Collins or Goldenhar syndrome.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:98943	Coloboma of eye lens	FZD5;SALL2;ABCB6;PAX6	4	A rare, genetic, developmental defect of the eye characterized by a uni- or bilateral abnormal lens shape (contraction of the lens with a notch) due to segmentally defective, or absent, development of the zonule and flattening of the equator in the region of the zonular defect, typically manifesting with reduced visual acuity. Other ocular anomalies, such as iris, choroid or optic disc colobomas, as well as cataracts and retinal detachment, may be associated.	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:98944	Coloboma of iris	ACTG1;FZD5;SALL2;ABCB6;PAX6	5	"A rare, genetic, developmental defect of the eye characterized by a uni- or bilateral notch, gap, hole or fissure, typically located in the inferonasal quadrant of the eye, involving only the pigment epithelium or the iris stroma (incomplete) or involving both (complete), manifesting with iris shape anomalies (e.g. ""keyhole"" or oval pupil) and/or photophobia. Association with colobomata in other parts of the eye (incl. ciliary body, zonule, choroid, retina, optic nerve) and complex malformation syndromes (such as CHARGE syndrome) may be observed."	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:98957	Gelatinous drop-like corneal dystrophy	TACSTD2	1	Gelatinous drop-like corneal dystrophy (GDCD) is a form of superficial corneal dystrophy characterized by multiple prominent milky-white gelatinous nodules beneath the corneal epithelium, and marked visual impairment.	Rare genetic eye disease
Orphanet:98956	Epithelial basement membrane dystrophy	TGFBI	1	NA	Rare genetic eye disease
Orphanet:98954	Meesmann corneal dystrophy	KRT12;KRT3	2	Meesmann corneal dystrophy (MECD) is a rare form of superficial corneal dystrophy characterized by distinct tiny bubble-like, round-to-oval punctate bilateral opacities in the central corneal epithelium, and to a lesser extent in the peripheral cornea, with little impact on vision.	Rare genetic eye disease
Orphanet:98964	Lattice corneal dystrophy type I	TGFBI	1	Type I lattice corneal dystrophy (LCDI) is a frequent form of stromal corneal dystrophy (see this term) characterized by a network of delicate interdigitating branching filamentous opacities within the cornea with progressive visual impairment and no systemic manifestations.	Rare genetic eye disease
Orphanet:98963	Granular corneal dystrophy type II	TGFBI	1	Type II granular corneal dystrophy (GCDII) is a rare form of stromal corneal dystrophy (see this term) characterized by irregular-shaped well-demarcated granular deposits in the superficial central corneal stroma, and progressive visual impairment.	Rare genetic eye disease
Orphanet:98962	Granular corneal dystrophy type I	TGFBI	1	Type I granular corneal dystrophy (GCDI) is a rare form of stromal corneal dystrophy (see this term) characterized by multiple small deposits in the superficial central corneal stroma, and progressive visual impairment, which may sometimes be severe.	Rare genetic eye disease
Orphanet:98961	Reis-Bücklers corneal dystrophy	TGFBI	1	Reis-Bücklers corneal dystrophy (RBCD), also known as granular corneal dystrophy type III, is a rare form of superficial corneal dystrophy characterized by bilateral symmetrical reticular opacities in the superficial central cornea, with progressive visual impairment.	Rare genetic eye disease
Orphanet:98960	Thiel-Behnke corneal dystrophy	TGFBI	1	Thiel-Behnke corneal dystrophy (TBCD) is a rare form of superficial corneal dystrophy characterized by sub-epithelial honeycomb-shaped corneal opacities in the superficial cornea, and progressive visual impairment.	Rare genetic eye disease
Orphanet:98973	Posterior polymorphous corneal dystrophy	VSX1;ZEB1;COL8A2;OVOL2;GRHL2	5	A rare mild subtype of posterior corneal dystrophy characterized by small aggregates of apparent vesicles bordered by a gray haze at the level of Descemet membrane, generally with no effect on vision.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:98974	Fuchs endothelial corneal dystrophy	SLC4A11;ZEB1;COL8A2;TCF4;AGBL1	5	A disorder that is the most frequent form of posterior corneal dystrophy and is characterized by excrescences on a thickened Descemet membrane (corneal guttae), generalized corneal edema, with gradually decreased visual acuity.	Rare genetic eye disease
Orphanet:98967	Schnyder corneal dystrophy	UBIAD1	1	Schnyder corneal dystrophy (SCD) is a rare form of stromal corneal dystrophy (see this term) characterized by corneal clouding or crystals within the corneal stroma, and a progressive decrease in visual acuity.	Rare genetic eye disease
Orphanet:98969	Macular corneal dystrophy	CHST6	1	Macular corneal dystrophy (MCD) is a rare, severe form of stromal corneal dystrophy (see this term) characterized by bilateral ill-defined cloudy regions within a hazy stroma, and eventually severe visual impairment.	Rare genetic eye disease
Orphanet:98970	Fleck corneal dystrophy	PIKFYVE	1	Fleck corneal dystrophy (FCD) is a rare generally asymptomatic form of stromal corneal dystrophy (see this term) characterized by multiple asymptomatic, non-progressive opacities disseminated throughout the corneal stroma with no effect on visual acuity.	Rare genetic eye disease
Orphanet:98975	Congenital hereditary endothelial dystrophy type I	OVOL2	1	A rare subtype of posterior corneal dystrophy characterized by a diffuse ground-glass appearance of the corneas and marked corneal thickening from birth or infancy without nystagmus, with blurred vision.	Rare genetic eye disease
Orphanet:98976	Congenital glaucoma	CYP1B1;MYOC;LTBP2;TEK	4	A developmental glaucoma that results from the abnormal development of the aqueous drainage structure, characterized by an elevated intra-ocular pressure, enlargement of globe (buphthalmos), corneal edema and optic nerve cupping, and presenting clinically with the characteristic triad of epiphora, photophobia and blepharospasm.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:98977	Juvenile glaucoma	CYP1B1;MYOC	2	A rare autosomal dominant open angle glaucoma, characterized by early onset, severe elevation of intra ocular pressure of rapid progression, leading to optic nerve excavation and, when untreated, substantial visual impairment.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:98978	Axenfeld anomaly	PITX2;FOXC1	2	A rare, congenital, ocular defect caused by anterior segment dysgenesis and characterized by anteriorly displaced Schwalbe's line and iris bands extending into the cornea. In contrast, Rieger's anomaly includes characteristic iris and pupil anomalies.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:98988	Early-onset anterior polar cataract	CRYAA;CRYBB3;CRYGB;CRYBA2	4	NA	NA
Orphanet:98990	Coralliform cataract	CRYGD	1	NA	NA
Orphanet:98989	Cerulean cataract	CRYBB2;CRYGD;MIP;MAF	4	A type of hereditary congenital cataract, distinguished by bluish and white opacifications in the superficial layers of the fetal lens nucleus and adult lens nucleus, and characterized by reduced visual acuity in childhood, eventually necessitating extraction of the lens.	NA
Orphanet:98984	Pulverulent cataract	BFSP2;CRYBB2;CRYGC;CRYGD;GJA3;GJA8;CRYBB1;MAF;VIM	9	NA	NA
Orphanet:98985	Early-onset sutural cataract	BFSP2;CRYBA1;CRYBB2;GJA8;MIP;CRYGS	6	NA	NA
Orphanet:98991	Early-onset nuclear cataract	WFS1;CRYAA;CRYAB;CRYBA1;CRYBB2;CRYBB3;CRYGC;CRYGD;GJA3;GJA8;MIP;CRYBB1;NHS;BFSP1;EPHA2;FYCO1;UNC45B;CRYBA2	18	NA	NA
Orphanet:98994	Total early-onset cataract	CRYAA;CRYBB2;GJA8;HSF4;MIP;NHS;LIM2;EPHA2;FYCO1;AGK;CRYGB;GCNT2;LSS;LEMD2;SIPA1L3	15	NA	Rare genetic developmental defect during embryogenesis;Rare genetic eye disease
Orphanet:98993	Early-onset posterior polar cataract	PITX3;CRYAB;CRYBA1;GJA3;MIP;CHMP4B;EPHA2	7	NA	NA
Orphanet:99001	Butterfly-shaped pigment dystrophy	PRPH2;OTX2;CTNNA1	3	A rare patterned dystrophy of the retinal pigment epithelium characterized by abnormal accumulation of lipofuscin in a butterfly-shaped distribution at the retinal pigment epithelium level. Patients manifest with a slowly progressive loss of vision that often only becomes apparent in old age.	Rare genetic eye disease
Orphanet:99002	Reticular dystrophy of the retinal pigment epithelium	RCBTB1	1	A rare, patterned dystrophy of the retinal pigment epithelium, of progressive course, characterized by the presence of a bilateral hyperpigmented reticular pattern resembling a fishnet with knots, resulting in a slowly progressive loss of vision that often only becomes apparent in old age. This disorder is sometimes associated with scleral staphyloma, choroidal neovascularization, convergent strabismus, spherophakia with myopia and luxated lenses, and partial atrophy of the iris.	Rare genetic eye disease
Orphanet:99000	Adult-onset foveomacular vitelliform dystrophy	PRPH2;BEST1;IMPG2;IMPG1	4	A rare, genetic, macular dystrophy characterized by blurred vision, metamorphopsia and mild visual impairment secondary to a slightly elevated, yellow, egg yolk-like lesion located in the foveal or parafoveal region.	Rare genetic eye disease
Orphanet:99003	Multifocal pattern dystrophy simulating fundus flavimaculatus	PRPH2	1	A rare, patterned dystrophy of the retinal pigment epithelium characterized by multiple yellowish irregular flecks scattered or interconnected around the macula, simulating what is observed in Stargardt disease, and usually asymptomatic until adulthood when patients present with a slowly progressive loss of vision that often only becomes apparent in old age.	Rare genetic eye disease
Orphanet:99013	Spastic paraplegia type 7	SPG7	1	A form of hereditary spastic paraplegia characterized by an onset usually in adulthood (but ranging from 10-72 years) of progressive bilateral lower limb weakness and spasticity, sphincter dysfunction, decreased vibratory sense at the ankles and with additional manifestations including optical neuropathy, nystagmus, strabismus, decreased hearing, scoliosis, pes cavus, motor and sensory neuropathy, amyotrophy, blepharoptosis and ophthalmoplegia.	Rare genetic eye disease;Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:99014	X-linked Charcot-Marie-Tooth disease type 5	PRPS1	1	X-linked Charcot-Marie-Tooth disease type 5 is a rare, genetic, peripheral sensorimotor neuropathy characterized by an X-linked recessive inheritance pattern and the infancy- to childhood-onset of: 1) progressive distal muscle weakness and atrophy (first appearing and more prominent in the lower extremities than the upper) which usually manifests with foot drop and gait disturbance, 2) bilateral, profound, prelingual sensorineural hearing loss and 3) progressive optic neuropathy. Females are asymptomatic and do not display the phenotype.	Rare inborn errors of metabolism;Rare genetic eye disease;Rare genetic neurological disorder;Genetic otorhinolaryngologic disease
Orphanet:99015	Spastic paraplegia type 2	PLP1	1	A rare, X-linked leukodystrophy characterized primarily by spastic gait and autonomic dysfunction. When additional central nervous system (CNS) signs, such as intellectual deficit, ataxia, or extrapyramidal signs, are present, the syndrome is referred to as complicated SPG.	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:99027	Adult-onset autosomal dominant leukodystrophy	LMNB1	1	A rare, slowly progressive neurological disorder involving centralnervous systemdemyelination, leading to autonomic dysfunction, ataxia and mild cognitive impairment.	Rare genetic eye disease;Rare genetic neurological disorder;Rare chromosomal anomaly
Orphanet:99042	Congenitally uncorrected transposition of the great arteries with coarctation	CFC1	1	NA	Rare genetic developmental defect during embryogenesis
Orphanet:98676	Autosomal recessive isolated optic atrophy	ACO2;RTN4IP1	2	A rare hereditary optic atrophy characterized by an early onset of bilateral optic nerve degeneration without other systemic features. Clinical manifestations include pallor of the optic disks, severe but slowly progressing visual impairment, and in some patients also paracentral scotoma, photophobia and dyschromatopsia.	Rare genetic eye disease
Orphanet:98673	Autosomal dominant optic atrophy, classic form	OPA1;DNM1L	2	One of the most common forms of hereditary optic neuropathy characterized by progressive bilateral visual loss during the first decade of life, associated with optic disc pallor, visual field and color vision defects.	Rare genetic eye disease;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:98619	Rare isolated myopia	SCO2;P3H2;LRPAP1	3	Rare isolated myopia is a rare, genetic, refraction anomaly disorder characterized by non-syndromic severe myopia, which may be associated with cataract and vitreoretinal degeneration (retinal detachment) that may lead to blindness.	Rare genetic eye disease
Orphanet:98795	Angelman syndrome due to paternal uniparental disomy of chromosome 15	UBE3A	1	NA	Rare genetic neurological disorder;Rare chromosomal anomaly
Orphanet:98794	Angelman syndrome due to maternal 15q11q13 deletion	UBE3A;OCA2	2	NA	Rare genetic neurological disorder;Rare chromosomal anomaly
Orphanet:98791	Alpha-thalassemia-intellectual disability syndrome linked to chromosome 16	HBA2;HBA1	2	A syndrome linked to chromosome 16 (ATR-16), a contiguous gene deletion syndrome, is a form of alpha-thalassemia characterized by microcytosis, hypochromia, normal hemoglobin (Hb) level or mild anemia, associated with developmental abnormalities.	Rare genetic neurological disorder;Rare chromosomal anomaly;Rare genetic hematologic disease
Orphanet:98806	Primary dystonia, DYT6 type	THAP1	1	Primary dystonia DYT6 type is characterized by focal, predominantly cranio-cervical dystonia with dysarthria and dysphagia, or limb dystonia in some cases.	Rare genetic neurological disorder
Orphanet:98805	Primary dystonia, DYT4 type	TUBB4A	1	DYT4 type primary dystonia is characterized by predominantly laryngeal dystonia (manifesting as whispering dysphonia) and cervical dystonia (manifesting as torticollis).	Rare genetic neurological disorder
Orphanet:98784	Autosomal dominant nocturnal frontal lobe epilepsy	CHRNA4;CHRNA2;CHRNB2;KCNT1;DEPDC5;CRH	6	A rare seizure disorder characterized by intermittent dystonia and/or choreoathetoid movements that occur during sleep. The clusters of nocturnal motor seizures are often stereotyped and brief.	Rare genetic neurological disorder
Orphanet:98764	Spinocerebellar ataxia type 27	FGF14	1	Spinocerebellar ataxia type 27 (SCA27) is a very rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by early-onset tremor, dyskinesia, and slowly progressive cerebellar ataxia.	Rare genetic neurological disorder
Orphanet:98763	Spinocerebellar ataxia type 14	PRKCG	1	Spinocerebellar ataxia type 14 (SCA14) is a rare mild subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by slowly progressive ataxia, dysarthria and nystagmus.	Rare genetic neurological disorder
Orphanet:98766	Spinocerebellar ataxia type 5	SPTBN2	1	Spinocerebellar ataxia type 5 (SCA5) is a rare subtype of autosomal dominant cerebellar ataxia type III (ADCA type III; see this term) characterized by the early-onset of cerebellar signs with eye movement abnormalities and a very slow disease progression.	Rare genetic neurological disorder
Orphanet:98765	Spinocerebellar ataxia type 4	PLEKHG4	1	Spinocerebellar ataxia type 4 (SCA4) is a very rare progressive and untreatable subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term) characterized by ataxia with sensory neuropathy.	Rare genetic neurological disorder
Orphanet:98760	Spinocerebellar ataxia type 8	ATXN8;ATXN8OS	2	Spinocerebellar ataxia type 8 (SCA8) is a subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term) characterized by cerebellar ataxia and cognitive dysfunction in almost three quarters of patients and pyramidal and sensory signs in approximately a third of patients.	Rare genetic neurological disorder
Orphanet:98759	Spinocerebellar ataxia type 17	TBP	1	Spinocerebellar ataxia type 17 (SCA17) is a rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by a variable clinical picture which can include dementia, psychiatric disorders, parkinsonism, dystonia, chorea, spasticity, and epilepsy.	Rare genetic neurological disorder
Orphanet:98762	Spinocerebellar ataxia type 12	PPP2R2B	1	Spinocerebellar ataxia type 12 (SCA12) is a very rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by the presence of action tremor associated with relatively mild cerebellar ataxia. Associated pyramidal and extrapyramidal signs and dementia have been reported.	Rare genetic neurological disorder
Orphanet:98761	Spinocerebellar ataxia type 10	ATXN10	1	Spinocerebellar ataxia type 10 (SCA10) is a subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by slowly progressive cerebellar syndrome and epilepsy, sometimes mild pyramidal signs, peripheral neuropathy and neuropsychological disturbances.	Rare genetic neurological disorder
Orphanet:98772	Spinocerebellar ataxia type 19/22	KCND3	1	Spinocerebellar ataxia type 19 (SCA19) is a very rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by mild cerebellar ataxia, cognitive impairment, low scores on the Wisconsin Card Sorting Test measuring executive function, myoclonus, and postural tremor.	Rare genetic neurological disorder
Orphanet:98771	Spinocerebellar ataxia type 18	IFRD1	1	Spinocerebellar ataxia type 18 (SCA18) is a very rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by sensory neuropathy and cerebellar ataxia.	Rare genetic neurological disorder
Orphanet:98773	Spinocerebellar ataxia type 21	TMEM240	1	Spinocerebellar ataxia type 21 (SCA21) is a very rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by slowly progressive cerebellar ataxia, mild cognitive impairment, postural and/or resting tremor, bradykinesia, and rigidity.	Rare genetic neurological disorder
Orphanet:98768	Spinocerebellar ataxia type 13	KCNC3	1	Spinocerebellar ataxia type 13 (SCA13) is a very rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by onset in childhood marked by delayed motor and cognitive development followed by mild progression of cerebellar ataxia.	Rare genetic neurological disorder
Orphanet:98767	Spinocerebellar ataxia type 11	TTBK2	1	Spinocerebellar ataxia type 11 (SCA11) is a subtype of autosomal dominant cerebellar ataxia type III (ADCA type III; see this term) characterized by the early-onset of cerebellar signs, eye movement abnormalities and pyramidal signs.	Rare genetic neurological disorder
Orphanet:98769	Spinocerebellar ataxia type 15/16	ITPR1	1	Spinocerebellar ataxia type 15/16 (SCA15/16) is a rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by cerebellar ataxia, tremor and cognitive impairment.	Rare genetic neurological disorder
Orphanet:98755	Spinocerebellar ataxia type 1	ATXN1	1	Spinocerebellar ataxia type 1 (SCA1) is a subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term) characterized by dysarthria, writing difficulties, limb ataxia, and commonly nystagmus and saccadic abnormalities.	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:98756	Spinocerebellar ataxia type 2	ATXN2	1	Spinocerebellar ataxia type 2 (SCA2) is a subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term) characterized by truncal ataxia, dysarthria, slowed saccades and less commonly ophthalmoparesis and chorea.	Rare genetic neurological disorder;Rare genetic eye disease
Orphanet:98758	Spinocerebellar ataxia type 6	CACNA1A	1	Spinocerebellar ataxia type 6 (SCA6) is the most common subtype of autosomal dominant cerebellar ataxia type III (ADCA type III; see this term) characterized by late-onset and slowly progressive gait ataxia and other cerebellar signs such as impaired muscle coordination and nystagmus.	Rare genetic neurological disorder
Orphanet:98754	Prader-Willi syndrome due to maternal uniparental disomy of chromosome 15	SNRPN;MAGEL2;NDN;OCA2	4	NA	Rare genetic gynecological and obstetrical diseases;Rare genetic endocrine disease;Genetic infertility;Rare genetic developmental defect during embryogenesis;Rare chromosomal anomaly
Orphanet:98434	Hereditary combined deficiency of vitamin K-dependent clotting factors	GGCX;VKORC1	2	Combined vitamin K-dependent clotting factors deficiency (VKCFD) is a congenital bleeding disorder resulting from variably decreased levels of coagulation factors II, VII, IX and X, as well as natural anticoagulants protein C, protein S and protein Z.	Rare inborn errors of metabolism;Rare genetic hematologic disease
Orphanet:104077	Myopathic intestinal pseudoobstruction	ACTG2	1	NA	Rare genetic gastroenterological disease
Orphanet:103918	Tropical pancreatitis	SPINK1;CTRC	2	Tropical pancreatitis is a rare pancreatic disease of juvenile onset occurring mainly in tropical developing countries and characterized by chronic non-alcoholic pancreatitis manifesting with abdominal pain, steatorrhea and fibrocalculous pancreatopathy (see this term). It is also commonly associated with the development of pancreatic calculi and pancreatic cancer at a much higher frequency than seen in ordinary chronic pancreatitis.	
Orphanet:103908	Congenital sodium diarrhea	SPINT2;SLC9A3	2	Congenital sodium diarrhea is characterized by severe watery diarrhea containing high concentrations of sodium, hyponatremia and metabolic acidosis.	Rare genetic gastroenterological disease
Orphanet:103909	Trehalase deficiency	TREH	1	A rare, genetic, intestinal disease characterized by osmotic diarrhea, abdominal pain and increased rectal flatulence after ingestion of trehalose, a disaccharide found mainly in mushrooms, due to intestinal trehalase deficiency. It occurs primarily in the Greenland population, although cases have also been reported elsewhere.	Rare inborn errors of metabolism;Rare genetic gastroenterological disease
Orphanet:102724	Acute myeloid leukemia with t(8;21)(q22;q22) translocation	RUNX1;FLT3;CEBPA;RUNX1T1;KIT	5	A rare acute myeloid leukemia with recurrent genetic anomaly disorder characterized by a t(8;21)(q22;q22) balanced translocation cytogenetic abnormality, forming a RUNX1-RUNX1T1 fusion gene, presenting with morphological characteristics which include myeloblasts with indented nuclei, basophilic cytoplasm with a prominent paranuclear hof that may contain a few azurophilic granules, prominent and possibly large promyelocytes, myelocytes and metamyelocytes, easily identifiable Auer rods and, more variably, bone marrow eosinophilia. Myeloid sarcoma is frequently present at diagnosis. Detection of the t(8;21)(q22;22) translocation is sufficient for diagnosis irrespective of blast count.	
Orphanet:101351	Familial isolated congenital asplenia	NKX2-5;RPSA	2	Familial isolated congenital asplenia is a rare, non-syndromic, potentially life-threatening visceral malformation characterized by the absence of normal spleen function, resulting in a primary immunodeficiency. Typically, the condition manifests with severe, recurrent, overwhelming infections (especially pneumococcal sepsis) in otherwise apparently healthy infants. In adults with no history of severe sepsis in infancy, thrombocytosis may be the presenting sign. Howell-Jolly bodies on blood smears and an absent spleen on abdominal ultrasound examination are highly suggestive associated findings.	Rare genetic immune disease;Rare genetic developmental defect during embryogenesis
Orphanet:101150	Autosomal recessive dopa-responsive dystonia	TH	1	A very rare neurometabolic disorder characterized by a spectrum of symptoms ranging from those seen in dopa-responsive dystonia (DRD) to progressive infantile encephalopathy.	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:101111	Spinocerebellar ataxia type 25	SCA25	1	Spinocerebellar ataxia type 25 (SCA25) is a very rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by cerebellar ataxia and prominent sensory neuropathy.	Rare genetic neurological disorder
Orphanet:101112	Spinocerebellar ataxia type 26	EEF2	1	Spinocerebellar ataxia type 26 (SCA26) is a very rare subtype of autosomal dominant cerebellar ataxia type III (ADCA type III; see this term) characterized by late-onset and slowly progressive cerebellar signs (gait ataxia) and eye movement abnormalities.	Rare genetic neurological disorder
Orphanet:101109	Spinocerebellar ataxia type 28	AFG3L2	1	Spinocerebellar ataxia type 28 (SCA28) is a very rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by juvenile onset, slowly progressive cerebellar ataxia due to Purkinje cell degeneration.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism
Orphanet:101110	Spinocerebellar ataxia type 20	SCA20	1	Spinocerebellar ataxia type 20 (SCA20) is a very rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by cerebellar dysarthria as the initial typical manifestation.	Rare genetic neurological disorder
Orphanet:101108	Spinocerebellar ataxia type 23	PDYN	1	Spinocerebellar ataxia type 23 (SCA23) is a very rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by gait ataxia, dysarthria, slowed saccades, ocular dysmetria, Babinski sign and hyperreflexia.	Rare genetic neurological disorder
Orphanet:101085	Charcot-Marie-Tooth disease type 1F	NEFL	1	 gene (8p21.2).	Rare genetic neurological disorder
Orphanet:101088	X-linked hyper-IgM syndrome	CD40LG	1	NA	Rare genetic immune disease
Orphanet:101081	Charcot-Marie-Tooth disease type 1A	PMP22	1	NA	Rare chromosomal anomaly;Rare genetic neurological disorder
Orphanet:101082	Charcot-Marie-Tooth disease type 1B	MPZ	1	age 40), with normal or mildly slowed MNCV and more frequent hearing loss and pupillary abnormalities. CMT1B can also cause the classical CMT phenotype in about 15% of total CMT1B cases.	Rare genetic neurological disorder
Orphanet:101083	Charcot-Marie-Tooth disease type 1C	LITAF	1	A rare, autosomal dominant, hereditary, demyelinating motor and sensory neuropathy which may present either as a classic Charcot-Marie-Tooth disease phenotype with distal motor weakness and wasting, gait difficulties, parethesias, decreased vibration and pain sensation, or as a milder, predominantly sensory form with transient paresthesias, decreased sensation and distal pain in upper or lower limbs, without significant motor weakness. Pes cavus is a common feature, and additional symptoms may include hand tremor and decreased or absent deep tendon reflexes.	Rare genetic neurological disorder
Orphanet:101084	Charcot-Marie-Tooth disease type 1D	EGR2	1	 gene (10q21.1), with a variable severity and age of onset (from infancy to adulthood), that usually presents with gait abnormalities, progressive wasting and weakness of distal limb muscles, with possible later involvement of proximal muscles, foot deformity and severe reduction in nerve conduction velocity. Additional features may include scoliosis, cranial nerve deficits such as diplopia, and bilateral vocal cord paresis.	Rare genetic neurological disorder
Orphanet:101078	X-linked Charcot-Marie-Tooth disease type 4	AIFM1	1	X-linked Charcot-Marie-Tooth disease type 4 is a rare, genetic, axonal, peripheral sensorimotor neuropathy characterized by an X-linked recessive inheritance pattern and the neonatal- to early childhood-onset of severe, slowly progressive, distal muscle weakness and atrophy (in particular of the peroneal group), as well as sensory impairment (with the lower extremities being more affected than the upper extremities), pes cavus, areflexia and hammertoes. Sensorineural hearing loss and cognitive impairment may also be associated. Females are asymptomatic and do not display the phenotype.	Rare genetic neurological disorder;Genetic otorhinolaryngologic disease
Orphanet:101075	X-linked Charcot-Marie-Tooth disease type 1	GJB1	1	X-linked Charcot-Marie-Tooth disease type 1 is a rare, genetic, peripheral sensorimotor neuropathy characterized by an X-linked dominant inheritance pattern and the childhood-onset (within the first decade in males) of progressive, distal, moderate to severe muscle weakness and atrophy in lower extremities and intrinsic hand muscles, pes cavus, bilateral foot drop, reduced or absent tendon reflexes, as well as mild to moderate sensory impairment in lower extremities. Females tend to have milder manifestations or may be asymptomatic. Sensorineural deafness and central nervous system involvement have also been reported.	Rare genetic neurological disorder;Genetic otorhinolaryngologic disease
Orphanet:101102	Charcot-Marie-Tooth disease type 2H	GDAP1	1	Charcot-Marie-Tooth disease, type 2H (CMT2H, also referred to as CMT4C2) is an axonal CMT peripheral sensorimotor polyneuropathy associated with pyramidal involvement.	Rare genetic neurological disorder
Orphanet:101101	Charcot-Marie-Tooth disease type 2B2	MED25	1	Charcot-Marie-Tooth disease, type 2B2 (CMT2B2, also referred to as CMT4C3) is an axonal CMT peripheral sensorimotor polyneuropathy that has been described in a large consanguineous Costa Rican family of Spanish ancestry.	Rare genetic neurological disorder
Orphanet:101097	Autosomal recessive Charcot-Marie-Tooth disease with hoarseness	GDAP1	1	A severe, early-onset form of axonal CMT peripheral sensorimotor polyneuropathy.	Rare genetic neurological disorder
Orphanet:101090	Hyper-IgM syndrome type 3	CD40	1	NA	Rare genetic immune disease
Orphanet:101089	Hyper-IgM syndrome type 2	AICDA	1	NA	Rare genetic immune disease
Orphanet:101092	Hyper-IgM syndrome type 5	UNG	1	NA	Rare genetic immune disease
Orphanet:101049	Familial hypocalciuric hypercalcemia type 2	GNA11	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic endocrine disease
Orphanet:101050	Familial hypocalciuric hypercalcemia type 3	AP2S1	1	NA	Rare genetic developmental defect during embryogenesis;Rare genetic bone disease;Rare genetic endocrine disease
Orphanet:101041	Familial hypofibrinogenemia	FGA;FGB;FGG	3	Familial hypofibrinogenemia is a coagulation disorder characterized by mild bleeding symptoms following trauma or surgery due to a reduced plasma fibrinogen concentration.	Rare genetic hematologic disease
Orphanet:101046	Autosomal dominant epilepsy with auditory features	RELN;LGI1;DEPDC5	3	A rare, genetic, familial partial epilepsy disease characterized by focal seizures associated with prominent ictal auditory symptoms, and/or receptive aphasia, presenting in two or more family members and having a relatively benign evolution.	Rare genetic neurological disorder
Orphanet:101068	Congenital stromal corneal dystrophy	DCN	1	Congenital stromal corneal dystrophy (CSCD) is an extremely rare form of stromal corneal dystrophy (see this term) characterized by opaque flaky or feathery clouding of the corneal stroma, and moderate to severe visual loss.	Rare genetic eye disease
Orphanet:101070	Bilateral frontoparietal polymicrogyria	ADGRG1	1	Bilateral frontoparietal polymicrogyria (BFPP) is a sub-type of polymicrogyria (PMG; see this term), a cerebral cortical malformation characterized by excessive cortical folding and abnormal cortical layering, that involves the frontoparietal region of the brain and that presents with hypotonia, developmental delay, moderate to severe intellectual disability, pyramidal signs, epileptic seizures, non progressive cerebellar ataxia, dysconjugate gaze and/or strabismus.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:101063	Situs inversus totalis	ANKS3;NME7;CITED2;NODAL;CFAP53;CFAP52;MMP21;PKD1L1	8	A rare, genetic, developmental defect during embryogenesis characterized by total mirror-image transposition of both thoracic and abdominal viscera across the left-right axis of the body. Congenital abnormalities, such as primary ciliary dyskinesia, Kartagener type, polysplenia syndrome, biliary atresia, congenital heart disease, and midgut malrotation, as well as vascular anomalies (e.g. absence of retrohepatic inferior vena cava, preduodenal portal vein, aberrant hepatic arterial anatomy) and malignancy, are frequently associated.	Rare genetic developmental defect during embryogenesis
Orphanet:101023	Cleft hard palate	GRHL3;UBB	2	NA	
Orphanet:101009	Autosomal dominant spastic paraplegia type 29	SPG29	1	A complex form of hereditary spastic paraplegia characterized by a spastic paraplegia presenting in adolescence, associated with the additional manifestations of sensorial hearing impairment due to auditory neuropathy and persistent vomiting due to a hiatal or paraesophageal hernia.	Rare genetic neurological disorder
Orphanet:101010	Autosomal spastic paraplegia type 30	KIF1A	1	Autosomal spastic paraplegia type 30 is a form of hereditary spastic paraplegia characterized by either a pure spastic paraplegia phenotype, usually presenting in the first or second decade of life, with spastic lower extremities, unsteady spastic gait, hyperreflexia and extensor plantar responses, or as a complicated phenotype with the additional manifestations of distal wasting, saccadic ocular movements, mild cerebellar ataxia and mild, distal, axonal neuropathy.	Rare genetic neurological disorder
Orphanet:101011	Autosomal dominant spastic paraplegia type 31	REEP1	1	30 years). In some cases, it can present as a complex phenotype with additional associated manifestations including peripheral neuropathy, bulbar palsy (with dysarthria and dysphagia), distal amyotrophy, and impaired distal vibration sense.	Rare genetic neurological disorder
Orphanet:101016	Romano-Ward syndrome	TRDN;SCN5A;CAV3;ANK2;KCNE1;KCNE2;KCNH2;KCNQ1;AKAP9;SCN4B;SNTA1;KCNJ5;NOS1AP;CALM1;CALM2;SCN10A	16	Romano-Ward syndrome (RWS) is an autosomal dominant variant of the long QT syndrome (LQTS, see this term) characterized by syncopal episodes and electrocardiographic abnormalities (QT prolongation, T-wave abnormalities and torsade de pointes (TdP) ventricular tachycardia).	Rare genetic cardiac disease
Orphanet:101039	Female restricted epilepsy with intellectual disability	PCDH19	1	Female restricted epilepsy with intellectual disability is a rare X-linked epilepsy syndrome characterized by febrile or afebrile seizures (mainly tonic-clonic, but also absence, myoclonic, and atonic) starting in the first years of life and, in most cases, developmental delay and intellectual disability of variable severity. Behavioral disturbances (e.g. autistic features, hyperactivity, and aggressiveness) are also frequently associated. This disease affects exclusively females, with male carriers being unaffected, despite an X-linked inheritance.	Rare genetic neurological disorder
Orphanet:101028	Transaldolase deficiency	TALDO1	1	Transaldolase deficiency is an inborn error of the pentose phosphate pathway that presents in the neonatal or antenatal period with hydrops fetalis, hepatosplenomegaly, hepatic dysfunction, thrombocytopenia, anemia, and renal and cardiac abnormalities.	Rare inborn errors of metabolism
Orphanet:100984	Autosomal dominant spastic paraplegia type 3	ATL1	1	A rare, pure or complex subtype of hereditary spastic paraplegia, with highly variable phenotype, typically characterized by childhood-onset of minimally progressive, bilateral, mainly symmetric lower limb spasticity and weakness, associated with pes cavus, diminished vibration sense, sphincter disturbances and/or urinary bladder hyperactivity. Additional associated manifestations may include scoliosis, mild intellectual disability, optic atrophy, axonal motor neuropathy and/or distal amyotrophy.	Rare genetic neurological disorder
Orphanet:100991	Autosomal dominant spastic paraplegia type 10	KIF5A	1	A rare type of hereditary spastic paraplegia that can present as either a pure form of spastic paraplegia with lower limb spasticity, hyperreflexia and extensor plantar responses, presenting in childhood or adolescence, or as a complex phenotype associated with additional manifestations including peripheral neuropathy with upper limb amyotrophy, moderate intellectual disability and parkinsonism. Deafness and retinitis pigmentosa were reported in one case.	Rare genetic neurological disorder
Orphanet:100989	Autosomal dominant spastic paraplegia type 8	WASHC5	1	A pure or complex form of hereditary spastic paraplegia characterized by a childhood to adulthood onset of slowly progressive lower limb spasticity resulting in gait disturbances, hyperreflexia and extensor plantar responses, that may be associated with complicating signs, such as upper limb involvement, sensory neuropathy, ataxia (i.e. mild dysmetria, uncoordinated eye movement) and mild dysphagia. Additional symptoms, including urinary urgency and/or incontinence, muscle weakness, decreased vibration sense and mild muscular atrophy in lower extremities, may also be associated.	Rare genetic neurological disorder
Orphanet:100988	Autosomal dominant spastic paraplegia type 6	NIPA1	1	A rare form of hereditary spastic paraplegia which usually presents in late adolescence or early adulthood as a pure phenotype of lower limb spasticity with hyperreflexia and extensor plantar responses, as well as mild bladder disturbances and pes cavus. Rarely, it can present as a complex phenotype with additional manifestations including epilepsy, variable peripheral neuropathy and/or memory impairment.	Rare genetic neurological disorder
Orphanet:100986	Autosomal recessive spastic paraplegia type 5A	CYP7B1	1	Autosomal recessive spastic paraplegia type 5A is a form of hereditary spastic paraplegia characterized by either a pure phenotype of slowly progressive spastic paraplegia of the lower extremities with bladder dysfunction and pes cavus or a complex presentation with additional manifestations including cerebellar signs, nystagmus, distal or generalized muscle atrophy and cognitive impairment. Age of onset is highly variable, ranging from early childhood to adulthood. White matter hyperintensity and cerebellar and spinal cord atrophy may be noted, on brain magnetic resonance imaging, in some patients.	Rare genetic neurological disorder
Orphanet:100985	Autosomal dominant spastic paraplegia type 4	SPAST	1	A rare form of hereditary spastic paraplegia with high intrafamilial clinical variability, characterized in most cases as a pure phenotype with an adult onset (mainly the 3rd to 5th decade of life, but that can present at any age) of progressive gait impairment due to bilateral lower-limb spasticity and weakness as well as very mild proximal weakness and urinary urgency. In some cases, a complex phenotype is also reported with additional manifestations including cognitive impairment, cerebellar ataxia, epilepsy and neuropathy. A faster disease progression is noted in patients with a later age of onset.	Rare genetic neurological disorder
Orphanet:100999	Autosomal dominant spastic paraplegia type 19	SPG19	1	A pure form of hereditary spastic paraplegia characterized by a slowly progressive and relatively benign spastic paraplegia presenting in adulthood with spastic gait, lower limb hyperreflexia, extensor plantar responses, bladder dysfunction (urinary urgency and/or incontinence), and mild sensory and motor peripheral neuropathy.	Rare genetic neurological disorder
Orphanet:101000	Autosomal recessive spastic paraplegia type 20	SPART	1	 gene (13q13.1), which encodes the protein spartin.	Rare genetic neurological disorder
Orphanet:100997	X-linked spastic paraplegia type 16	SPG16	1	A complex, hereditary, spastic paraplegia characterized by delayed motor development, spasticity, and inability to walk, later progressing to quadriplegia, motor aphasia, bowel and bladder dysfunction. Patients also present with vision problems and mild intellectual disability. The disease affects only males.	Rare genetic neurological disorder
Orphanet:100998	Autosomal dominant spastic paraplegia type 17	BSCL2	1	A complex hereditary spastic paraplegia characterized by progressive spastic paraplegia, upper and lower limb muscle atrophy, hyperreflexia, extensor plantar responses, pes cavus and occasionally impaired vibration sense. Association with hand muscles amyotrophy typical.	Rare genetic neurological disorder
Orphanet:100995	Autosomal recessive spastic paraplegia type 14	SPG14	1	Autosomal recessive spastic paraplegia type 14 is a rare, complex hereditary spastic paraplegia characterized by adulthood-onset of slowly progressive spastic paraplegia of lower limbs presenting with spastic gait, hyperreflexia, and mild lower limb hypertonicity associated with mild intellectual disability, visual agnosia, short and long-term memory deficiency and mild distal motor neuropathy. Bilateral pes cavus and extensor plantar responses are also associated.	Rare genetic neurological disorder
Orphanet:100996	Autosomal recessive spastic paraplegia type 15	ZFYVE26	1	Autosomal recessive spastic paraplegia type 15 is a complex form of hereditary spastic paraplegia characterized by a childhood to adulthood onset of slowly progressive lower limb spasticity (resulting in gait disturbance, extensor plantar responses and decreased vibration sense) associated with mild intellectual disability, mild cerebellar ataxia, peripheral neuropathy (with distal upper limb amyotrophy) and retinal degeneration. Thin corpus callosum is a common imaging finding.	Rare genetic neurological disorder
Orphanet:100993	Autosomal dominant spastic paraplegia type 12	RTN2	1	A pure form of hereditary spastic paraplegia characterized by a childhood- to adulthood-onset of slowly progressive lower limb spasticity and hyperreflexia of lower extremities, extensor plantar reflexes, distal sensory impairment, variable urinary dysfunction and pes cavus.	Rare genetic neurological disorder
Orphanet:100994	Autosomal dominant spastic paraplegia type 13	HSPD1	1	A rare hereditary spastic paraplegia characterized by progressive spastic paraplegia with pyramidal signs in the lower limbs, decreased vibration sense, and increased reflexes in the upper limbs.	Rare genetic neurological disorder
Orphanet:101007	Autosomal recessive spastic paraplegia type 27	SPG27	1	Autosomal recessive spastic paraplegia type 27 is a rare, pure or complex hereditary spastic paraplegia characterized by a variable onset of slowly progressive lower limb spasticity, hyperreflexia and extensor plantar responses, that may be associated with sensorimotor polyneuropathy, decreased vibration sense, lower limb distal muscle wasting, dysarthria and mild to moderate intellectual disability.	Rare genetic neurological disorder
Orphanet:101008	Autosomal recessive spastic paraplegia type 28	DDHD1	1	Autosomal recessive spastic paraplegia type 28 is a pure form of hereditary spastic paraplegia characterized by a childhood or adolescent onset of slowly progressive, pure crural muscle spastic paraparesis which manifests with mild lower limb weakness, gait difficulties, extensor plantar responses, and hyperreflexia of lower extremities. Less common manifestations include cerebellar oculomotor disturbance with saccadic eye pursuit, pes cavus and scoliosis. Some patients also present pin and vibration sensory loss in distal legs.	Rare genetic neurological disorder
Orphanet:101005	Autosomal recessive spastic paraplegia type 25	SPG25	1	Autosomal recessive spastic paraplegia type 25 (SPG25) is a rare, complex type of hereditary spastic paraplegia characterized by adult-onset spastic paraplegia associated with spinal pain that radiates to the upper or lower limbs and is related to disk herniation (with minor spondylosis), as well as mild sensorimotor neuropathy. The SPG25 phenotype has been mapped to a locus on chromosome 6q23-q24.1.	Rare genetic neurological disorder
Orphanet:101006	Autosomal recessive spastic paraplegia type 26	B4GALNT1	1	 gene (12q13.3), encoding Beta-1, 4 N-acetylgalactosaminyltransferase 1.	Rare genetic neurological disorder
Orphanet:101003	Autosomal recessive spastic paraplegia type 23	DSTYK;SPG23	2	Autosomal recessive spastic paraplegia type 23 (SPG23) is a rare, complex type of hereditary spastic paraplegia that presents in childhood with progressive spastic paraplegia, associated with peripheral neuropathy, skin pigment abnormalities (i.e. vitiligo, hyperpigmentation, diffuse lentigines), premature graying of hair, and characteristic facies (i.e. thin with ''sharp'' features). The SPG23 phenotype has been mapped to a locus on chromosome 1q24-q32.	Rare genetic neurological disorder
Orphanet:101004	Autosomal recessive spastic paraplegia type 24	SPG24	1	A very rare, pure form of spastic paraplegia characterized by an onset in infancy of lower limb spasticity associated with gait disturbances, scissor gait, tiptoe walking, clonus and increased deep tendon reflexes. Mild upper limb involvement may occasionally also be associated.	Rare genetic neurological disorder
Orphanet:101001	Autosomal recessive spastic paraplegia type 21	SPG21	1	Autosomal recessive spastic paraplegia type 21 is a complex type of hereditary spastic paraplegia characterized by an onset in adolescence or adulthood of slowly progressive spastic paraparesis associated with the additional manifestations of apraxia, cognitive and speech decline (leading to dementia and akinetic mutism in some cases), personality disturbances and extrapyramidal (e.g. oromandibular dyskinesia, rigidity) and cerebellar (i.e. dysdiadochokinesia and incoordination) signs. Subtle abnormalities (e.g. developmental delays) may be noted earlier in childhood. A thin corpus callosum and white matter abnormalities are equally reported on magnetic resonance imaging.	Rare genetic neurological disorder
Orphanet:100093	Carcinoid syndrome	SDHD	1	A rare neoplastic disease characterized by the occurrence of a hormonal syndrome resulting from secretion of humoral factors (including polypeptides, vasoactive amines, and prostaglandins) from a functional neuroendocrine tumor (particularly from the midgut), typically manifesting with increased bowel movements and diarrhea, episodic vasoactive flushes (particularly of the face), hypotension, tachycardia, venous telangiectasia, dyspnea, and bronchospasms, as well as long-term fibrotic changes in the mesentery, retroperitoneum, and of the cardiac valves.	
Orphanet:100924	Porphyria due to ALA dehydratase deficiency	ALAD	1	Porphyria of doss or deficiency of delta-aminolevulinic acid dehydratase (DALAD) is an extremely rare form of acute hepatic porphyria (see this term) characterized by neuro-visceral attacks without cutaneous manifestations.	Rare genetic neurological disorder;Rare genetic skin disease;Rare genetic renal disease;Rare inborn errors of metabolism
Orphanet:100973	FRAXE intellectual disability	AFF2;FMR3	2	FRAXE is a form of nonsyndromic X-linked mental retardation (NS-XLMR) characterized by mild intellectual deficit. FRAXE is the most common form of NS-XLMR.	Rare genetic neurological disorder
Orphanet:100974	FRAXF syndrome	TMEM185A	1	FRAXF syndrome was originally identified in a family with developmental delay and an expanded CCG repeat at the folate-sensitive FRAXF fragile site. Since this initial description, FRAXF has been associated with a range of manifestations but no clear phenotype has been established.	
Orphanet:100976	Bathing suit ichthyosis	TGM1	1	Bathing suit ichthyosis (BSI) is a rare variant of autosomal recessive congenital ichthyosis (ARCI; see this term) characterized by the presence of large dark scales in specific areas of the body.	Rare genetic skin disease;Rare genetic eye disease;Rare genetic developmental defect during embryogenesis
Orphanet:100054	F12-related hereditary angioedema with normal C1Inh	F12	1	Hereditary angioedema type 3 (HAE 3) is a form of hereditary angioedema (see this term) characterized by acute edema in subcutaneous tissues, viscera and/or the upper airway.	
Orphanet:100051	Hereditary angioedema type 2	SERPING1	1	Hereditary angioedema type 2 (HAE 2) is a form of hereditary angioedema (see this term) characterized by acute edema in subcutaneous tissues, viscera and/or the upper airway.	Serpinopathy
Orphanet:100057	Renin-angiotensin-aldosterone system-blocker-induced angioedema	XPNPEP2	1	Renin-angiotensin-aldosterone system (RAAS)-blocker induced angioedema (RAE) is a type of acquired angioedema (AAE, see this term) characterized by acute edema in subcutaneous tissues, viscera and/or the upper airway.	
Orphanet:100069	Semantic dementia	PSEN1;TMEM106B;CHMP2B;TREM2;MAPT;GRN;C9ORF72	7	Semantic dementia (SD) is a form of frontotemporal dementia (FTD; see this term), characterized by the progressive, amodal and profound loss of semantic knowledge (combination of visual associative agnosia, anomia, surface dyslexia or dysgraphia and disrupted comprehension of word meaning) and behavioral abnormalities, attributable to the degeneration of the anterior temporal lobes.	Rare genetic neurological disorder
Orphanet:100070	Progressive non-fluent aphasia	TMEM106B;PSEN1;CHMP2B;TREM2;VCP;MAPT;GRN;C9ORF72	8	Progressive non-fluent aphasia (PNFA) is a form of frontotemporal dementia (FTD; see this term), characterized by agrammatism, laborious speech, alexia, and agraphia, frequently accompanied by apraxia of speech (AOS). Language comprehension is relatively preserved.	Rare genetic neurological disorder
Orphanet:100075	Neuroendocrine tumor of stomach	ATRX;DAXX	2	Gastric neuroendocrine tumor is a rare subtype of neuroendocrine neoplasm, arising from enterochromaffin-like cells in the stomach, with a variable clinical presentation, disease course and prognosis, depending on the disease type and histological grade. Most patients are asymptomatic, with diagnosis usually occurring incidentally during gastroscopy, however, symptoms of dyspepsia, anemia, pain, weight loss and gastrointestinal bleeding can be observed. Association with Zollinger-Ellison syndrome and multiple endocrine neoplasia type I has been reported.	
Orphanet:100032	Hypocalcified amelogenesis imperfecta	FAM83H;SLC24A4;ITGB6;AMTN	4	NA	Rare genetic odontologic disease
Orphanet:100031	Hypoplastic amelogenesis imperfecta	ACP4;ENAM;LAMB3;ITGB6;AMBN	5	NA	Rare genetic odontologic disease
Orphanet:100034	Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism	DLX3	1	NA	Rare genetic odontologic disease
Orphanet:100033	Hypomaturation amelogenesis imperfecta	GPR68;AMELX;KLK4;MMP20;WDR72;ODAPH;SLC24A4	7	NA	Rare genetic odontologic disease
Orphanet:100044	Autosomal dominant intermediate Charcot-Marie-Tooth disease type B	DNM2	1	A rare hereditary motor and sensory neuropathy characterized by intermediate motor median nerve conduction velocities (usually between 25 and 45 m/s) and signs of both demyelination and axonal degeneration in nerve biopsies. It presents with mild to moderately severe, slowly progressive usual clinical features of Charcot-Marie-Tooth disease (muscle weakness and atrophy of the distal extremities, distal sensory loss, reduced or absent deep tendon reflexes, and feet deformities). Other findings include asymptomatic neutropenia and early-onset cataracts.	Rare genetic neurological disorder
Orphanet:100045	Autosomal dominant intermediate Charcot-Marie-Tooth disease type C	YARS	1	A rare hereditary motor and sensory neuropathy characterized by intermediate motor median nerve conduction velocities (usually between 25 and 60 m/s). It presents with moderately severe, slowly progressive usual clinical features of Charcot-Marie-Tooth disease (muscle weakness and atrophy of the distal extremities, distal sensory loss, reduced or absent deep tendon reflexes, feet deformities, extensor digitorum brevis atrophy). Findings in nerve biopsies include age-dependent axonal degeneration, reduced number of large myelinated fibres, segmental remyelination, and no onion bulbs.	Rare genetic neurological disorder
Orphanet:100046	Autosomal dominant intermediate Charcot-Marie-Tooth disease type D	MPZ	1	A rare hereditary motor and sensory neuropathy characterized by intermediate motor median nerve conduction velocities (usually between 25 and 45 m/s) and signs of both axonal degeneration and demyelination without onion bulbs in nerve biopsies. It presents with usual Charcot-Marie-Tooth disease clinical features of variable severity (progressive muscle weakness and atrophy of the distal extremities, distal sensory loss, reduced or absent deep tendon reflexes, and feet deformities). Other findings in some of the families include debilitating neuropathic pain and mild postural/kinetic upper limb tremor.	Rare genetic neurological disorder
Orphanet:100050	Hereditary angioedema type 1	SERPING1	1	A form of hereditary angioedema characterized by acute edema in subcutaneous tissues, viscera and/or the upper airway.	Serpinopathy
Orphanet:100008	ACys amyloidosis	CST3	1	A form of HCHWA characterized by an age of onset of 20-30 years, systemic amyloidosis and recurrent lobar intracerebral hemorrhages.	Rare genetic neurological disorder;Rare genetic systemic or rheumatologic disease
Orphanet:100006	ABeta amyloidosis, Dutch type	APP	1	Hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D) is a form of HCHWA (see this term), a group of familial central nervous system disorders, characterized by severe cerebral amyloid angiopathy (CAA), hemorrhagic and non-hemorrhagic strokes and dementia.	Rare genetic neurological disorder;Rare genetic systemic or rheumatologic disease
Orphanet:99989	Intermediate DEND syndrome	KCNJ11	1	Intermediate DEND syndrome (iDEND) is a rare mild form of DEND syndrome (see this term), a neonatal diabetes mellitus, developmental delay and epilepsy condition. The intermediate form is characterized clinically by mild motor, speech or cognitive delay and an absence of epilepsy.	Rare genetic neurological disorder;Rare genetic endocrine disease
Orphanet:99977	Squamous cell carcinoma of the esophagus	WWOX;RNF6;TGFBR2;DLEC1	4	Esophageal squamous cell carcinoma (ESCC) is a type of esophageal carcinoma (EC; see this term) that can affect any part of the esophagus, but is usually located in the upper or middle third.	
Orphanet:99971	Well-differentiated liposarcoma	CDK4;HMGA2;MDM2	3	Well-differentiated liposarcoma (WDLS), the most common type of liposarcoma (LS; see this term), is a slow growing, painless tumor usually located in the retroperitoneum or the limbs. It is composed of proliferating mature adipocytes.	
Orphanet:99970	Dedifferentiated liposarcoma	CDK4;HMGA2;MDM2	3	Dedifferentiated liposarcoma (DDLS) is a high-grade subtype of liposarcoma (LS; see this term) that progresses from well-differentiated liposarcoma (WDLS; see this term), and most often occurs in the retroperitoneum. It is defined as a region of nonlipogenic sarcoma associated with WDLS. .	
Orphanet:99967	Myxoid/round cell liposarcoma	FUS;DDIT3	2	Myxoid/round cell liposarcoma (MRCLS) is a type of liposarcoma (LS; see this term) mostly located in the limbs, with a variable behavior depending on the histological subtype. Both myxoid and round cell are distinct histological subtypes of LS.	
Orphanet:99966	Atypical teratoid rhabdoid tumor	SMARCB1	1	A rare, highly malignant central nervous system (CNS) rhabdoid tumor (RT) found almost exclusively in children.	
Orphanet:99961	Benign recurrent intrahepatic cholestasis type 2	ABCB11	1	NA	Rare inborn errors of metabolism;Rare genetic hepatic disease
Orphanet:99960	Benign recurrent intrahepatic cholestasis type 1	ATP8B1	1	NA	Rare inborn errors of metabolism;Rare genetic hepatic disease
Orphanet:99955	Charcot-Marie-Tooth disease type 4B1	MTMR2	1	Charcot-Marie-Tooth disease type 4B1 (CMT4B1) is a subtype of Charcot-Marie-Tooth disease type 4 characterized by an early childhood-onset of severe, demyelinating sensorimotor neuropathy, various degrees of complex myelin outfoldings seen on peripheral nerve biopsy, very slow, and often undetectable, nerve conduction velocities, and the typical CMT phenotype (i.e. distal muscle weakness and atrophy, sensory loss, and frequent pes cavus). Other reported features include facial weakness, vocal cord paresis, respiratory difficulties, and skeletal deformities (e.g. chest deformities, claw hands, pes equinovarus).	Rare genetic neurological disorder
Orphanet:99956	Charcot-Marie-Tooth disease type 4B2	SBF2	1	Charcot-Marie-Tooth disease type 4B2 (CMT4B2) is a subtype of Charcot-Marie-Tooth type 4 characterized by a severe, early childhood-onset of demyelinating sensorimotor neuropathy, early-onset glaucoma, focally folded myelin sheaths in the peripheral nerves, severely reduced nerve conduction velocities, and the typical CMT phenotype (i.e. distal muscle weakness and atrophy, sensory loss, and frequent pes cavus). Severe visual impairment leading to visual loss has also been reported.	Rare genetic neurological disorder
Orphanet:99948	Charcot-Marie-Tooth disease type 4A	GDAP1	1	Charcot-Marie-Tooth disease type 4A (CMT4A) is a subtype of Charcot-Marie-Tooth disease type 4 characterized by early-onset (infancy to early childhood) of severe, rapidly progressing demyelinating, axonal, or intermediate sensorimotor neuropathy usually affecting first, and more severely, the distal lower extremities and later the proximal muscles and upper extremities. Nerve conduction velocities range from very slow to normal. Apart from the typical CMT phenotype (distal muscle weakness and atrophy, sensory loss, frequent pes cavus foot deformity), patients commonly present delayed motor development, vocal cord paresis, mild sensory loss, abolished deep tendon reflexes, and skeletal deformities.	Rare genetic neurological disorder
Orphanet:99947	Autosomal dominant Charcot-Marie-Tooth disease type 2A2	MFN2	1	A subtype of Autosomal dominant Charcot-Marie-Tooth disease type 2 characterized by the childhood onset of distal weakness and areflexia (with earlier and more severe involvement of the lower extremities), reduced sensory modalities (primarily pain and temperature sensation), foot deformities, postural tremor, scoliosis and contractures. Optic atrophy, vocal cord palsy with dysphonia, sensorineural hearing loss, spinal cord abnormalities and hydrocephalus have also been reported.	Rare genetic neurological disorder
Orphanet:99950	Charcot-Marie-Tooth disease type 4D	NDRG1	1	Charcot-Marie-Tooth disease type 4D (CMT4D) is a subtype of Charcot-Marie-Tooth disease type 4 characterized by a childhood-onset of severe, progressive, demyelinating sensorimotor neuropathy manifesting with distal muscle weakness and atrophy, sensorineural hearing impairment leading to deafness (usually in third decade), severely reduced nerve conduction velocities, and skeletal, especially foot, deformities. Tongue atrophy has also been reported.	Rare genetic neurological disorder
Orphanet:99949	Charcot-Marie-Tooth disease type 4C	SH3TC2	1	Charcot-Marie-Tooth disease type 4C (CMT4C) is a subtype of Charcot-Marie-Tooth type 4 characterized by childhood or adolescent-onset of a relatively mild, demyelinating sensorimotor neuropathy that contrasts with a severe, rapidly progressing, early-onset scoliosis, and the typical CMT phenotype (i.e. distal muscle weakness and atrophy, sensory loss, and often foot deformity). A wide spectrum of nerve conduction velocities are observed and cranial nerve involvement and kyphoscoliosis have also been reported.	Rare genetic neurological disorder
Orphanet:99952	Charcot-Marie-Tooth disease type 4F	PRX	1	Charcot-Marie-Tooth disease type 4F (CMT4F) is a severe, demyelinating subtype of Charcot-Marie-Tooth disease type 4 characterized by the childhood onset of a slowly-progressing typical CMT phenotype (i.e. distal muscle weakness and atrophy, as well as pes cavus) that presents severe sensory loss (frequently with sensory ataxia), moderately to severely reduced motor nerve conduction velocities and almost invariable absence of sensory nerve action potentials, and delayed motor milestones.	Rare genetic neurological disorder
Orphanet:99951	Charcot-Marie-Tooth disease type 4E	EGR2	1	Charcot-Marie-Tooth disease type 4E (CMT4E) is a congenital, hypomyelinating subtype of Charcot-Marie-Tooth disease type 4 characterized by a Dejerine-Sottas syndrome-like phenotype (incl. hypotonia and/or delayed motor development in infancy), extremely slow nerve conduction velocities, potential respiratory dysfunction, cranial nerve involvement, and the typical CMT phenotype, i.e. distal muscle weakness and atrophy, sensory loss, and foot deformity.	Rare genetic neurological disorder
Orphanet:99954	Charcot-Marie-Tooth disease type 4H	FGD4	1	Charcot-Marie-Tooth disease type 4H is a subtype of Charcot-Marie-Tooth disease type 4 characterized by onset before two years of age of severe, slowly progressive, demyelinating sensorimotor neuropathy manifesting with delayed motor development (walking), unsteady gait, distal muscle weakness and atrophy (more prominent in the lower limbs), areflexia, mild symmetrical stocking-distribution hypoesthesia, and skeletal malformations (incl. kyphoscoliosis, short neck, pes cavus and pes equinus). Severely reduced nerve conduction velocities are associated.	Rare genetic neurological disorder
Orphanet:99953	Charcot-Marie-Tooth disease type 4G	HK1	1	Charcot-Marie-Tooth disease type 4G (CMT4G) is a subtype of Charcot-Marie-Tooth disease type 4 characterized by early childhood onset of progressive distal muscle weakness and atrophy, delayed motor development, prominent distal sensory impairment, areflexia, moderately reduced nerve conduction velocities, and foot and hand deformities in Balkan (Russe) Gypsies.	Rare genetic neurological disorder
Orphanet:99940	Autosomal dominant Charcot-Marie-Tooth disease type 2F	HSPB1	1	A form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy, characterized by symmetric weakness primarily occurring in the lower limbs (distal muscles in a majority of cases) and reaching the arms only after 5 to 10 years, occasional and predominantly distal sensory loss and reduced tendon reflexes. It presents with gait anomaly between the 1st and 6th decade and early onset is generally associated to a more severe phenotype which may include foot drop.	Rare genetic neurological disorder
Orphanet:99939	Autosomal dominant Charcot-Marie-Tooth disease type 2E	NEFL	1	A form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy, with onset in the first to 6th decade with a gait anomaly and a leg weakness that reaches the arms secondarily. Tendon reflexes are reduced or absent and, after years, all patients have a pes cavus. Other signs may be present, including hearing loss and postural tremor.	Rare genetic neurological disorder
Orphanet:99942	Autosomal dominant Charcot-Marie-Tooth disease type 2I	MPZ	1	A form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy, characterized by a late onset with severe sensory loss (paresthesia and hypoesthesia) associated with distal weakness, mainly of the legs, and absent or reduced deep tendon reflexes.	Rare genetic neurological disorder
Orphanet:99944	Autosomal dominant Charcot-Marie-Tooth disease type 2K	GDAP1	1	An axonal Charcot-Marie-Tooth (CMT) peripheral sensorimotor polyneuropathy.	Rare genetic neurological disorder
Orphanet:99943	Autosomal dominant Charcot-Marie-Tooth disease type 2J	MPZ	1	A form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy, characterized by a relatively late onset, pupillary abnormalities and deafness, in most patients, associated with distal weakness and muscle atrophy.	Rare genetic neurological disorder
Orphanet:99946	Autosomal dominant Charcot-Marie-Tooth disease type 2A1	KIF1B	1	A form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy, presenting with a more prominent muscle weakness in lower than upper limbs and frequent postural tremor.	Rare genetic neurological disorder
Orphanet:99945	Autosomal dominant Charcot-Marie-Tooth disease type 2L	HSPB8	1	A form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy. In the single family reported to date, CMT2L onset is between 15 and 33 years. Patients present with a symmetric distal weakness of legs and occasionally of the hands, absent or reduced tendon reflexes, distal legs sensory loss and frequently a pes cavus. Progression is slow.	Rare genetic neurological disorder
Orphanet:99936	Autosomal dominant Charcot-Marie-Tooth disease type 2B	RAB7A	1	A severe form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy, with onset in the 2nd or 3rd decade, characterized by ulcerations and infections of feet. Symmetric and distal weakness develops mostly in the legs together with a severe symmetric distal sensory loss, tendon reflexes are only reduced at ankles and foot deformities, including pes cavus or planus and hammer toes, appear in childhood.	Rare genetic neurological disorder
Orphanet:99937	Autosomal dominant Charcot-Marie-Tooth disease type 2C	TRPV4	1	A form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy, characterized by the association of vocal cord anomalies, impairment of respiratory muscles and sensorineural hearing loss with the distal hands and feet weakness. Onset is between infancy and the 6th decade.	Rare genetic neurological disorder
Orphanet:99938	Autosomal dominant Charcot-Marie-Tooth disease type 2D	GARS	1	A form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy, characterized by distal weakness primarily and predominantly occurring in the upper limbs and tendon reflexes absent or reduced in the arms and decreased in the legs. Progression is slow.	Rare genetic neurological disorder
Orphanet:99916	Malignant Sertoli-Leydig cell tumor of the ovary	DICER1	1	Malignant Sertoli-Leydig cell tumor of ovary is a rare malignant sex cord stromal tumor of ovary (see this term) occuring typically in young women and characterized by manifestations of androgen excess (hirsutism, hair loss, amenorrhea, or oligomenorrhea), when functional.	
Orphanet:99915	Maligant granulosa cell tumor of the ovary	FOXL2;DICER1	2	Malignant granulosa cell tumor of ovary is a rare malignant sex cord stromal tumor of ovary (see this term) arising from the granulosa cells of the ovary, which occurs in peri and post menopausal women, and that presents with abnormal vaginal bleeding, abdominal pain and distension. The tumor is frequently unilateral, estrogen secreting, and has a slow natural history and a tendency to relapse long after the initial diagnosis, necessitating prolonged follow-up.	
Orphanet:99914	Gynandroblastoma	DICER1	1	NA	
Orphanet:99901	Acyl-CoA dehydrogenase 9 deficiency	ACAD9	1	A rare disorder characterized by neurological dysfunction, hepatic failure and cardiomyopathy due to a deficiency of complex I of the respiratory chain.	Rare genetic developmental defect during embryogenesis;Rare inborn errors of metabolism;Rare genetic cardiac disease
Orphanet:99900	Long chain acyl-CoA dehydrogenase deficiency	ACADL	1	NA	Rare genetic cardiac disease;Rare inborn errors of metabolism
Orphanet:99898	Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR1 deficiency	IFNGR1	1	Mendelian susceptibility to mycobacterial diseases (MSMD) due to complete interferon gamma receptor 1 (IFN-gammaR1) deficiency is a genetic variant of MSMD (see this term) characterized by a complete deficiency in IFN-gammaR1, leading to impaired IFN-gamma immunity and, consequently, to severe and often fatal infections with bacillus Calmette-Guérin (BCG) and other environmental mycobacteria (EM).	Rare genetic immune disease
Orphanet:99879	Familial isolated hyperparathyroidism	GCM2;CDC73;MEN1	3	A rare, hereditary, familial primary hyperparathyroidism disease characterized by primary hyperparathyroidism due to single or multiple parathyroid tumors in at least two first-degree relatives in the absence of evidence of other endocrine disorders, tumors and/or systemic manifestations.	Rare genetic endocrine disease
Orphanet:99880	Hyperparathyroidism-jaw tumor syndrome	CDC73	1	NA	Inherited cancer-predisposing syndrome;Rare genetic endocrine disease
Orphanet:99875	OBSOLETE: Ehlers-Danlos syndrome type 7A	COL1A1	1	NA	NA
Orphanet:99876	OBSOLETE: Ehlers-Danlos syndrome type 7B	COL1A2	1	NA	NA
Orphanet:99887	Acute megakaryoblastic leukemia in Down syndrome	GATA1	1	NA	
Orphanet:99885	Permanent neonatal diabetes mellitus	STAT3;ABCC8;GCK;KCNJ11;PDX1;INS	6	Permanent neonatal diabetes mellitus (PNDM) is a monogenic form of neonatal diabetes (NDM, see this term) characterized by persistent hyperglycemia within the first 12 months of life in general, requiring continuous insulin treatment.	Rare genetic endocrine disease
Orphanet:99886	Transient neonatal diabetes mellitus	ABCC8;KCNJ11;HYMAI;PLAGL1;ZFP57	5	Transient neonatal diabetes mellitus (TNDM) is a genetically heterogeneous form of neonatal diabetes (NDM, see this term) characterized by hyperglycemia presenting in the neonatal period that remits during infancy but recurs in later life in most patients.	Rare genetic endocrine disease
Orphanet:99860	Precursor B-cell acute lymphoblastic leukemia	PDGFRA;IKZF1;ABL1;RUNX1;BCR;CDKN2A;TP53;GATA3;KMT2A;FLT3;ETV6;AUTS2;HLF;AFF1;TCF3;PBX1;IGH;FOXP1;PAX5;PAX5;PIP4K2A;HLA-C	22	NA	
Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia	ABL1;SET;NUP214;ZBTB16;SALL2;TRA;BCR;CDKN2A;TAL1;FLT3;MYC;STIL;MYB;TRB;TRD;TRG;TCL1A;TLX1;TLX3;CNOT3;MLLT10;HNRNPH1;DDX3X;PICALM	24	NA	
Orphanet:99872	OBSOLETE: Hashimoto-Pritzker syndrome	BRAF	1	NA	NA
Orphanet:99849	Glycogen storage disease due to muscle beta-enolase deficiency	ENO3	1	Muscle beta-enolase deficiency is a glycolysis disorder reported in one patient to date and characterized clinically by exercise intolerance and myalgia due to severe enolase deficiency in muscle.	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:99845	Genetic recurrent myoglobinuria	MT-CO1;MT-CO3;LPIN1	3	Genetic recurrent myoglobinuria is an inborn error of metabolism characterized by abnormal urinary excretion of myoglobin due to acute destruction of skeletal muscle fibers.	Rare inborn errors of metabolism;Rare genetic neurological disorder
Orphanet:99843	Leukocyte adhesion deficiency type II	SLC35C1	1	Leukocyte adhesion deficiency type II (LAD-II) is a form of LAD (see this term) characterized by recurrent bacterial infections, severe growth delay and severe intellectual deficit.	Rare inborn errors of metabolism;Rare genetic eye disease;Rare genetic immune disease;Rare genetic neurological disorder
Orphanet:99844	Leukocyte adhesion deficiency type III	FERMT3	1	Leukocyte adhesion deficiency type III (LAD-III) is a form of LAD (see this term) characterized by both severe bacterial infections and a severe bleeding disorder.	Rare genetic eye disease;Rare genetic immune disease;Rare genetic developmental defect during embryogenesis;Rare genetic bone disease
Orphanet:99853	Ovarioleukodystrophy	EIF2B1;EIF2B2;EIF2B3;EIF2B4;EIF2B5;AARS2	6	NA	Rare genetic neurological disorder
Orphanet:99854	Cree leukoencephalopathy	EIF2B1;EIF2B2;EIF2B3;EIF2B4;EIF2B5	5	NA	Rare genetic neurological disorder
Orphanet:99852	Ravine syndrome	SLC7A2-IT1	1	Ravine syndrome is an extremely rare genetic neurological disorder, reported in a small number of patients in a specific community on Reunion Island (Ravine region), characterized by infantile anorexia with irrepressible and repeated vomiting, acute brainstem dysfunction, severe failure to thrive, and progressive encephalopathy with MRI showing vanishing of medulla oblongata and cerebellar white matter and severe atrophy of pons, along with supra-tentorial periventricular white-matter hyperintensities and basal ganglia anomalies.	Rare genetic neurological disorder
Orphanet:99832	Resistance to thyrotropin-releasing hormone syndrome	TRHR	1	Resistance to thyrotropin-releasing hormone (TRH) syndrome is a type of central congenital hypothyroidism (see this term) characterized by low levels of thyroid hormones due to insufficient release of thyroid-stimulating hormone (TSH) caused by pituitary resistance to TRH. It may or may not be observed from birth.	Rare genetic endocrine disease
Orphanet:99842	Leukocyte adhesion deficiency type I	ITGB2	1	Leukocyte adhesion deficiency type I (LAD-I) is a form of LAD (see this term) characterized by life-threatening, recurrent bacterial infections.	Rare genetic eye disease;Rare genetic immune disease
Orphanet:99811	Neuronal intestinal pseudoobstruction	FLNA	1	Neuronal intestinal pseudoobstruction is a form of chronic intestinal pseudoobstruction caused by a developmental failure of the enteric neurons to differentiate or migrate properly and manifests as a bowel obstruction.	Rare genetic gastroenterological disease
Orphanet:99812	LIG4 syndrome	XRCC4;LIG4	2	LIG4 syndrome is a hereditary disorder associated with impaired DNA double-strand break repair mechanisms and characterized by microcephaly, unusual facial features, growth and developmental delay, skin anomalies, and pancytopenia, which is associated with combined immunodeficiency (CID).	Rare genetic developmental defect during embryogenesis;Inherited cancer-predisposing syndrome;Rare genetic immune disease
Orphanet:99818	Turcot syndrome with polyposis	APC	1	Turcot syndrome with polyposis or Turcot syndrome type 2 is a form of familial adematous polyposis, characterized by the concurrence of thousands of colonic adenomatous polyposis or colorectal cancer (CRC) and a primary central nervous system tumor (principally medulloblastoma). It is also associated with pigmented ocular fundus lesions.	Rare genetic gastroenterological disease;Inherited cancer-predisposing syndrome;Rare genetic tumor
Orphanet:99819	Familial gestational hyperthyroidism	TSHR	1	NA	Rare genetic renal disease;Rare genetic endocrine disease
Orphanet:99796	Subcortical band heterotopia	DCX;PAFAH1B1;EML1	3	A rare, non-syndromic cerebral malformation due to abnormal neuronal migration characterized by variable clinical manifestation depending on the location, size and thickness of subcortical bands. Clinical presentation ranges from mild cognitive deficit to developmental delay with severe intellectual disability, seizures and behavioral problems.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:99798	Oligodontia	SUMO1;AXIN2;EDA;EDARADD;FGFR1;IRF6;WNT10A;MSX1;PAX9;TGFA;LRP6;WNT10B	12	Oligodontia is a rare developmental dental anomaly in humans characterized by the absence of six or more teeth.	Rare genetic odontologic disease
Orphanet:99802	Hemimegalencephaly	PIK3CA;AKT3	2	Hemimegalencephaly is a rare cerebral malformation characterized by overgrowth of all or part of a cerebral hemisphere, often with ipsilateral severe cortical dysplasia or dysgenesis, white matter hypertrophy and dilated lateral ventricle, presenting in early infancy with progressive hemiparesis, severe psychomotor retardation and intractable seizures. Hemimegalencephaly may be an isolated finding or associated with other syndromes such as angioosteohypertrophic syndrome, epidermal nevus syndrome and Ito hypomelanosis (see these terms). Management includes seizure control by antiepileptic medications and early hemispherectomy.	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:99803	Haddad syndrome	PHOX2B;RET;ASCL1	3	Haddad syndrome is a rare congenital disorder in which congenital central hypoventilation syndrome (CCHS), or Ondine syndrome, occurs concurrently with Hirschsprung disease (see these terms).	Rare genetic eye disease;Rare genetic gastroenterological disease;Rare genetic developmental defect during embryogenesis;Rare genetic neurological disorder
Orphanet:99806	Oculootodental syndrome	FGF3;FADD	2	A contiguous gene syndrome comprising otodental syndrome (characterized by globodontia and sensorineural high-frequency hearing deficit) associated with eye abnormalities including, typically, iris and chorioretinal coloboma, as well as, on occasion, microcornea, microphtalmos, lenticular opacity, lens coloboma and iris pigment epithelial atrophy.	Rare genetic developmental defect during embryogenesis;Rare chromosomal anomaly
Orphanet:99807	PEHO-like syndrome	CCDC88A	1	PEHO-like syndrome is a rare, genetic neurological disease characterized by progressive encephalopathy, early-onset seizures with a hypsarrhythmic pattern, facial and limb edema, severe hypotonia, early arrest of psychomotor development and craniofacial dysmorphism (evolving microcephaly, narrow forehead, short nose, prominent auricles, open mouth, micrognathia), in the absence of neuro-ophthalmic or neuroradiologic findings. Poor visual responsiveness, growth failure and tapering fingers are also associated.	Rare genetic skin disease;Rare genetic neurological disorder
Orphanet:99810	Familial porencephaly	COL4A1;COL4A2	2	NA	Rare genetic neurological disorder;Rare genetic developmental defect during embryogenesis
Orphanet:99789	Dentin dysplasia type I	SSUH2;DSPP;VPS4B	3	Dentin dysplasia type I (DD-I) is a rare form of dentin dysplasia (DD, see this term) characterized by sharp conical short roots or rootless teeth.	Rare genetic odontologic disease
Orphanet:99791	Dentin dysplasia type II	DSPP	1	Dentin dysplasia type II (DD-II) is a rare mild form of dentin dysplasia (DD, see this term) characterized by normal tooth roots but abnormal primary dentition.	Rare genetic odontologic disease
Orphanet:99763	OBSOLETE: Familial hyperreninemic hypoaldosteronism type 1	CYP11B2	1	NA	NA
Orphanet:99772	Cleft velum	GRHL3;UBB	2	Cleft velum is a fissure type embryopathy that affects in varying degrees the soft palate.	
Orphanet:99771	Bifid uvula	UBB;GRHL3	2	Bifid uvula is a fissure type embryopathy affecting the uvula at the back of the soft palate.