genitopatellar syndrome

description: 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.


Goldberg-Shprintzen syndrome

category: biolink:Disease biolink:DiseaseOrPhenotypicFeature biolink:BiologicalEntity biolink:ThingWithTaxon biolink:NamedThing

description: A multiple malformation syndrome characterized by Hirschprung megacolon with microcephaly, hypertelorism, submucous cleft palate, short stature and learning disability.


name: hereditary papillary renal cell carcinoma

description: A familial carcinoma inherited in an autosomal dominant trait. It is characterized by the development of multiple, bilateral papillary renal cell carcinomas. The carcinomas range from microscopic lesions to clinically symptomatic tumors. It is associated with activating mutations of the MET oncogene.


name: autosomal recessive nonsyndromic hearing loss 97

description: Any autosomal recessive nonsyndromic deafness in which the cause of the disease is a mutation in the MET gene.


osteofibrous dysplasia

description: A benign, usually self-limited fibro-osseous lesion of the bone that affects infants and children. It usually arises from the cortical bone of the anterior mid-shaft of the tibia. Patients usually present with swelling or painless bowing of the tibia. Progression to adamantinoma has been reported in some cases.


advanced sleep phase syndrome 2

description: Any advanced sleep phase syndrome in which the cause of the disease is a mutation in the CSNK1D gene.


aortic aneurysm, familial thoracic 9

description: Any familial thoracic aortic aneurysm and aortic dissection in which the cause of the disease is a mutation in the MFAP5 gene.


name: short-rib thoracic dysplasia 10 with or without polydactyly

description: An asphyxiating thoracic dystrophy that has material basis in homozygous or compound heterozygous mutation in the IFT172 gene on chromosome 2p23.


retinitis pigmentosa 71

description: Any retinitis pigmentosa in which the cause of the disease is a mutation in the IFT172 gene.


name: growth delay due to insulin-like growth factor I resistance

description: Growth delay due to IGF-I resistance is characterized 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).


name: T-B+ severe combined immunodeficiency due to gamma chain deficiency

description: Severe combined immunodeficiency (SCID) due to gamma chain deficiency, also called SCID-X1, is a form of SCID characterized by severe and recurrent infections, associated with diarrhea and failure to thrive.


leukocyte adhesion deficiency 1

description: Leukocyte adhesion deficiency type I (LAD-I) is a form of LAD characterized by life-threatening, recurrent bacterial infections.


lymphoproliferative syndrome 1

description: A condition of decreased or absent presence or activity of IL2-inducible t-cell kinase. Deficiency of this protein is associated with lymphoproliferative syndrome 1, an autosomal recessive primary immunodeficiency characterized by onset in early childhood of Epstein-Barr virus (EBV)-associated immune dysregulation, manifest as lymphoma, lymphomatoid granulomatosis, hemophagocytic lymphohistiocytosis, Hodgkin disease, and/or hypogammaglobulinemia..


ABri amyloidosis

description: A cerebral amyloid angiopathy characterized by onset in the 4th to 6th decade of life, progressive mental deterioration, spasticity, muscular rigidity but no tremors, spontaneous movements or sensory changes that has material basis in an autosomal dominant mutation of ITM2B on chromosome 13q14.2.


ADan amyloidosis

description: A cerebral amyloid angiopathy characterized by ataxia, intention tremor, psychosis and dementia that has material basis in an autosomal dominant mutation of ITM2B on chromosome 13q14.2.


name: retinal dystrophy with inner retinal dysfunction and ganglion cell anomalies

description: An autosomal dominant condition caused by mutation(s) in the ITM2B gene, encoding integral membrane protein 2B. It is characterized by progressive loss of central vision, and inner retinal dystrophy with ganglion cell abnormalities.


isovaleric acidemia

description: Isovaleric acidemia (IVA) is 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.


thyroid dyshormonogenesis 4

description: Any familial thyroid dyshormonogenesis in which the cause of the disease is a mutation in the IYD gene.


name: Alagille syndrome due to a JAG1 point mutation


name: deafness, congenital heart defects, and posterior embryotoxon


name: T-B+ severe combined immunodeficiency due to JAK3 deficiency

description: Severe combined immunodeficiency (SCID) T-B+ due to JAK3 deficiency is a form of SCID characterized by severe and recurrent infections, associated with diarrhea and failure to thrive.


name: porencephaly-microcephaly-bilateral congenital cataract syndrome


name: hypogonadotropic hypogonadism 1 with or without anosmia

description: The X-linked inherited form of Kallmann syndrome caused by mutation of the KAL1 gene mapped to chromosome Xp22.3.


Carney complex, type 1

description: Any Carney complex in which the cause of the disease is a mutation in the PRKAR1A gene.


name: pigmented nodular adrenocortical disease, primary, 1

description: Any primary pigmented nodular adrenocortical disease in which the cause of the disease is a mutation in the PRKAR1A gene.


name: Acrodysostosis 1 with or without hormone resistance

description: An autosomal dominant skeletal dysplasia caused by mutation(s) in the PRKAR1A gene, encoding cAMP-dependent protein kinase type I-alpha regulatory subunit. It is characterized by short stature, brachydactyly, and characteristic facial features. Resistance to multiple hormones is a common finding.


platelet-type bleeding disorder 19

description: Any isolated hereditary giant platelet disorder in which the cause of the disease is a mutation in the PRKACG gene.


name: intellectual disability, autosomal dominant 54


name: encephalopathy due to defective mitochondrial and peroxisomal fission 2


name: thyrotoxic periodic paralysis, susceptibility to, 2

description: Any thyrotoxic periodic paralysis in which the cause of the disease is a mutation in the KCNJ18 gene.


name: Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b;

description: An autosomal recessive sub-type of Charcot-Marie-Tooth disease caused by compound heterozygous or homozygous mutation(s) in the MFN2 gene, encoding mitofusin-2. This condition is more severe and has an earlier onset as compared to Charcot-Marie-Tooth disease type 2A2A.


Charcot-Marie-Tooth disease type 2A2

description: Autosomal dominant Charcot-Marie-Tooth disease type 2A2 (CMT2A2) is 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.


name: neuropathy, hereditary motor and sensory, type 6A

description: Any hereditary motor and sensory neuropathy type 6 in which the cause of the disease is a mutation in the MFN2 gene.


progressive myoclonic epilepsy type 7

description: Any progressive myoclonic epilepsy in which the cause of the disease is a mutation in the KCNC1 gene.


name: autosomal dominant nonsyndromic hearing loss 2A

description: Any autosomal dominant nonsyndromic deafness in which the cause of the disease is a mutation in the KCNQ4 gene.


name: intellectual disability, autosomal dominant 46


name: ectodermal dysplasia 12, hypohidrotic/hair/tooth/nail type

description: Any ectodermal dysplasia syndrome in which the cause of the disease is a mutation in the KDF1 gene.


name: spastic paraplegia, intellectual disability, nystagmus, and obesity


cranioectodermal dysplasia 3

description: Any cranioectodermal dysplasia in which the cause of the disease is a mutation in the IFT43 gene.


name: short-rib thoracic dysplasia 18 with polydactyly


asphyxiating thoracic dystrophy 2

description: Any Jeune syndrome in which the cause of the disease is a mutation in the IFT80 gene.


name: agammaglobulinemia 2, autosomal recessive

description: Any autosomal agammaglobulinemia in which the cause of the disease is a mutation in the IGLL1 gene.


Griscelli syndrome type 3

description: A Griscelli syndrome characterized by isolated silvery gray sheen of the hair and hypopigmentation of the skin that has material basis in mutation in the MLPH or MYO5A genes.


name: congenital muscular dystrophy due to integrin alpha-7 deficiency

description: 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.


retinitis pigmentosa 38

description: Any retinitis pigmentosa in which the cause of the disease is a mutation in the MERTK gene.


inosine triphosphatase deficiency

description: An inherited condition caused by mutation(s) in the ITPA gene, encoding inosine triphosphate pyrophosphatase. It is characterized by elevated concentrations of inosine triphosphate in erythrocytes.


name: developmental and epileptic encephalopathy, 35


spinocerebellar ataxia type 15/16

description: Spinocerebellar ataxia type 15/16 (SCA15/16) is a rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I). It is characterized by cerebellar ataxia, tremor and cognitive impairment.


spinocerebellar ataxia type 29

description: Spinocerebellar ataxia type 29 (SCA29) is a rare subtype of autosomal dominant cerebellar ataxia type I (ADCA type I) characterized by very slowly progressive or non-progressive ataxia, dysarthria, oculomotor abnormalities and intellectual disability.


name: aniridia-cerebellar ataxia-intellectual disability syndrome

description: Aniridia-cerebellar ataxia-intellectual disability syndrome, also known as Gillespie syndrome, is a rare, congenital, neurological disorder characterized by the association of partial bilateral aniridia with non-progressive cerebellar ataxia, and intellectual disability.


name: isolated anhidrosis with normal sweat glands

description: Any anhidrosis in which the cause of the disease is a mutation in the ITPR2 gene.


Joubert syndrome 26

description: Any Joubert syndrome in which the cause of the disease is a mutation in the KIAA0556 gene.


pachyonychia congenita 1

description: Any pachyonychia congenita in which the cause of the disease is a mutation in the KRT16 gene.


name: palmoplantar keratoderma, nonepidermolytic, focal 1

description: Any nonepidermolytic palmoplantar keratoderma in which the cause of the disease is a mutation in the KRT16 gene.


wooly hair, autosomal recessive 3

description: Any wooly hair in which the cause of the disease is a mutation in the KRT25 gene.


name: epidermolytic palmoplantar keratoderma, 1

description: A genetic skin disorder caused by mutations in the KRT9 gene. It is characterized by hyperkeratosis in the palms and soles resulting in abnormal thickening of the skin in these areas.


superficial epidermolytic ichthyosis

description: Superficial epidermolytic ichthyosis (SEI) is a rare keratinopathic ichthyosis (KI) characterized by the presence of superficial blisters and erosions at birth.


ichthyosis hystrix of Curth-Macklin

description: Ichthyosis hystrix of Curth-Macklin (IHCM) is a rare type of keratinopathic ichthyosis that is characterized by the presence of severe hyperkeratotic lesions and palmoplantar keratoderma (PPK).


name: diffuse nonepidermolytic palmoplantar keratoderma

description: A rare, genetic, isolated diffuse palmoplantar keratoderma characterized by diffuse, mild to thick, finely demarcated hyperkeratosis of palms and soles. Additional clinical findings include knuckle pad-like keratoses on fingers, hyperkeratosis of umbilicus and areolae, diffuse dry skin, hyperhidrosis, hangnails and frequent fungal infections. Histological examination of lesions reveals orthokeratotic hyperkeratosis, acanthosis, hypergranulosis, and mild lymphocyte infiltrations in the upper dermis with no evidence of epidermolysis.


ichthyosis, annular epidermolytic 1

description: Any annular epidermolytic ichthiosis in which the cause of the disease is a variation in the KRT10 gene.


keratosis palmoplantaris striata 3

description: Any striate palmoplantar keratoderma in which the cause of the disease is a mutation in the KRT1 gene.


white sponge nevus 1

description: Any hereditary mucosal leukokeratosis in which the cause of the disease is a mutation in the KRT4 gene.


pachyonychia congenita 3

description: Any pachyonychia congenita in which the cause of the disease is a mutation in the KRT6A gene.


pachyonychia congenita 4

description: Any pachyonychia congenita in which the cause of the disease is a mutation in the KRT6B gene.


name: palmoplantar keratoderma, nonepidermolytic, focal or diffuse


hypotrichosis 3

description: Any hypotrichosis in which the cause of the disease is a mutation in the KRT74 gene.


ectodermal dysplasia 7, hair/nail type

description: Any pure hair and nail ectodermal dysplasia in which the cause of the disease is a mutation in the KRT74 gene.


methylcobalamin deficiency type cblG

description: Methylcobalamin deficiency cbl G type is a rare condition that occurs when the body is unable to process certain amino acids (building blocks of protein) properly. In most cases, signs and symptoms develop during the first year of life; however, the age of onset can range from infancy to adulthood. Common features of the condition include feeding difficulties, lethargy, seizures, poor muscle tone (hypotonia), developmental delay, microcephaly (unusually small head size), and megaloblastic anemia. Methylcobalamin deficiency cbl G type is caused by changes (mutations) in the MTR gene and is inherited in an autosomal recessive manner. Treatment generally includes regular doses of hydroxycobalamin (vitamin B12). Some affected people may also require supplementation with folates and betaine.


name: psychomotor regression-oculomotor apraxia-movement disorder-nephropathy syndrome


retinitis pigmentosa 58

description: Any retinitis pigmentosa in which the cause of the disease is a mutation in the ZNF513 gene.


name: seborrhea-like dermatitis with psoriasiform elements


intellectual disability, X-linked 91

description: Any non-syndromic X-linked intellectual disability in which the cause of the disease is a mutation in the ZDHHC15 gene.


name: female infertility due to zona pellucida defect

description: 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.


name: intellectual disability, autosomal recessive 56

description: Any autosomal recessive non-syndromic intellectual disability in which the cause of the disease is a mutation in the ZC3H14 gene.


name: skeletal defects, genital hypoplasia, and intellectual disability


name: intellectual disability, autosomal dominant 22

description: Any autosomal dominant non-syndromic intellectual disability in which the cause of the disease is a mutation in the ZBTB18 gene.


name: syndromic X-linked intellectual disability Raymond type

description: A syndromic X-linked intellectual disability characterized by intellectual disability and marfanoid habitus that has material basis in mutation in the ZDHHC9 gene on chromosome Xq26.1.


spermatogenic failure 14

description: Any azoospermia in which the cause of the disease is a mutation in the ZMYND15 gene.


primary ciliary dyskinesia 22

description: Any primary ciliary dyskinesia in which the cause of the disease is a mutation in the ZMYND10 gene.


acromelic frontonasal dysostosis

description: Acromelic frontonasal dysplasia (AFND) is a rare variant of 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.


name: neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features


Primrose syndrome

description: 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.


name: intellectual disability, autosomal dominant 43

description: Any autosomal dominant non-syndromic intellectual disability in which the cause of the disease is a mutation in the HIVEP2 gene.


holoprosencephaly 5

description: Holoprosencephaly associated with mutations in the ZIC2 gene.


hereditary spastic paraplegia 15

description: 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.


name: global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies


brittle cornea syndrome 1

description: Any brittle cornea syndrome in which the cause of the disease is a mutation in the ZNF469 gene.


tuberous sclerosis 2

description: Tuberous sclerosis mapped to chromosome 16p13.3 (TSC2 gene).


lymphangioleiomyomatosis

description: A multifocal neoplasm with perivascular epithelioid cell differentiation affecting almost exclusively females of child-bearing age. It is characterized by the presence of smooth muscle and epithelioid cells and by the proliferation of lymphatic vessels. Sites of involvement include the lungs, mediastinum, and the retroperitoneum. It usually presents with chylous pleural effusion or ascites.


name: isolated focal cortical dysplasia type II

description: A type of focal cortical dysplasia that is characterized by disrupted cortical lamination and specific cytological abnormalities.


nephronophthisis 12

description: Any nephronophthisis in which the cause of the disease is a mutation in the TTC21B gene.


asphyxiating thoracic dystrophy 4

description: An asphyxiating thoracic dystrophy has material basis in compound heterozygous mutation in the TTC21B gene on chromosome 2q24.


name: mitochondrial complex III deficiency nuclear type 2

description: Any mitochondrial complex III deficiency in which the cause of the disease is a mutation in the TTC19 gene.


Amish lethal microcephaly

description: Amish lethal microcephaly is a very rare syndrome characterized by extreme microcephaly and early death, within the first year.


name: progressive demyelinating neuropathy with bilateral striatal necrosis

description: 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.


spinocerebellar ataxia type 41

description: 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.


juvenile Paget disease

description: 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.


name: myopathy, lactic acidosis, and sideroblastic anemia 1

description: Any myopathy, lactic acidosis, and sideroblastic anemia in which the cause of the disease is a mutation in the PUS1 gene.


sebaceous adenoma

description: A benign, well circumscribed neoplasm arising from the sebaceous glands. It usually presents as a small yellowish tumor in the sun exposed skin of head and neck. It is characterized by the presence of sebaceous cells aggregates with a peripheral rim of basaloid cells.


name: sudden infant death-dysgenesis of the testes syndrome

description: Sudden infant death with dysgenesis of the testes (SIDDT) syndrome is a lethal condition in infants with dysgenesis of testes.


name: gastrointestinal defects and immunodeficiency syndrome 1

description: A rare genetic disease characterized by multiple intestinal atresia in association with combined immunodeficiency and inflammatory bowel disease. Clinical features include widespread atresia extending from the stomach to the rectum, homogenous calcifications in the abdominal cavity, hepatic cholestasis, cirrhosis, and chronic liver failure, hypoplastic thymus, and increased susceptibility to mainly bacteria and viruses. The immunological phenotype consists of profound generalized T-cell lymphopenia and milder natural killer cell and B-cell lymphopenia, as well as low serum levels of IgG, IgA, and IgM, with elevated serum IgE. The disease is mostly fatal in infancy or childhood.


focal segmental glomerulosclerosis 2

description: Any focal segmental glomerulosclerosis in which the cause of the disease is a mutation in the TRPC6 gene.


name: early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome


trichorhinophalangeal syndrome type I

description: An autosomal dominant malformation syndrome caused by mutations in TRPS1 characterized by distinctive craniofacial and skeletal abnormalities. TRPS I patients have sparse scalp hair, bulbous tip of the nose, long flat philtrum, thin upper vermilion border, and protruding ears. Skeletal abnormalities include cone-shaped epiphyses at the phalanges, hip malformations, and short stature.


name: trichorhinophalangeal syndrome, type III

description: A trichorhinophalangeal syndrome caused by mutations in TRPS1 characterized by the presence of severe brachydactyly, due to short metacarpals, and severe short stature.


3-methylglutaconic aciduria type 5

description: A syndrome 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.


name: myopathy, myofibrillar, 9, with early respiratory failure


hypertrophic cardiomyopathy 9

description: Any hypertrophic cardiomyopathy in which the cause of the disease is a mutation in the TTN gene.


dilated cardiomyopathy 1G

description: Any familial isolated dilated cardiomyopathy in which the cause of the disease is a mutation in the TTN gene.


tibial muscular dystrophy

description: 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.


name: autosomal recessive limb-girdle muscular dystrophy type 2J

description: Autosomal recessive limb-girdle muscular dystrophy type 2J (LGMD2J) is 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.


name: early-onset myopathy with fatal cardiomyopathy


Joubert syndrome 14

description: Any Joubert syndrome in which the cause of the disease is a mutation in the TMEM237 gene.


autosomal recessive osteopetrosis 7

description: Any autosomal recessive malignant osteopetrosis in which the cause of the disease is a mutation in the TNFRS11A gene.


major depressive disorder

description: An episode of depression lasting two or more weeks without an intervening episode of mania.


name: attention deficit-hyperactivity disorder, susceptibility to, 7


name: intellectual disability, autosomal dominant 57


name: congenital myopathy 4B, autosomal recessive

description: Any congenital myopathy in which the cause of the disease is a mutation in the TPM3 gene.


name: congenital myopathy 4A, autosomal dominant


name: congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome

description: Congenital sideroblastic anemia -B cell immunodeficiency- periodic fever-developmental delay syndrome is a form of constitutional sideroblastic anemia, 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.


name: retinitis pigmentosa and erythrocytic microcytosis


name: autosomal recessive nonsyndromic hearing loss 6

description: Any autosomal recessive nonsyndromic deafness in which the cause of the disease is a mutation in the TMIE gene.


Waardenburg syndrome type 2D

description: Any Waardenburg syndrome type 2 in which the cause of the disease is a mutation in the SNAI2 gene.


piebaldism

description: 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.


congenital myasthenic syndrome 18

description: Any congenital myasthenic syndrome in which the cause of the disease is a mutation in the SNAP25 gene.


name: autoimmune lymphoproliferative syndrome type 1

description: A rare, primary immunodeficiency with an autosomal dominant pattern of inheritance but variable penetrance. It is the most common subtype of autoimmune lymphoproliferative syndrome (ALPS). It is usually caused by a germline mutation in the Fas gene that leads to defective Fas-induced apoptosis but in a minority of cases, it also may be attributed to a somatic Fas mutation. Disruption of Fas-induced apoptosis impairs lymphocyte homeostasis and immune tolerance. Characteristic laboratory findings include an increase in circulating, double-negative (CD4-/CD8-) T cells in the setting of immune-mediated anemia, thrombocytopenia and neutropenia. Clinical signs present in childhood include fatigue, pallor, bruising, hepatosplenomegaly and chronic, non-malignant, non-infectious lymphadenopathy. The clinical course is influenced by a strong association with other autoimmune disorders and an increased risk for developing Hodgkin and non-Hodgkin lymphoma.


hereditary spastic paraplegia 7

description: Autosomal recessive spastic paraplegia type 7 is 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.


dilated cardiomyopathy 1Z

description: Any familial isolated dilated cardiomyopathy in which the cause of the disease is a mutation in the TNNC1 gene.


hypertrophic cardiomyopathy 13

description: Any hypertrophic cardiomyopathy in which the cause of the disease is a mutation in the TNNC1 gene.


mast syndrome

description: 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.


mal de Meleda

description: Mal de Melada (MdM) is a diffuse palmoplantar keratoderma initially reported from of the Island of Meleda characterized by symmetric palmoplantar hyperkeratosis that progressively extends to the dorsal surfaces of hands and feet (transgradiens). The disease can be associated to hyperhidrosis, lichenoid plaques and perioral erythema.


familial pancreatic carcinoma

description: Familial pancreatic carcinoma is defined by the presence of pancreatic cancer (PC) in two or more first-degree relatives.


chromosome 10q23 deletion syndrome

description: 10q22.3q23.3 microdeletion syndrome is a rare partial autosomal monosomy characterized by a mild facial dysmorphism variably including macrocephaly, broad forehead, hypertelorism or hypotelorism, deep-set eyes, upslanting or downslanting palpebral fissures, low-set ears, flat nasal bridge, smooth philtrum, thin upper lip), cleft palate, cerebellar and cardiac malformations, psychomotor development delay, and behavioral abnormalities (attention deficit hyperactivity disorder, autism). Other rare features may include congenital breast aplasia, arachnodactyly, joint hyperlaxity, club feet, feeding difficulties, failure to thrive.


name: Juvenile Polyposis with Hereditary Hemorrhagic Telangiectasia


Myhre syndrome

description: Myhre syndrome is characterized 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.


autosomal recessive osteopetrosis 2

description: Any autosomal recessive malignant osteopetrosis in which the cause of the disease is a mutation in the TNFSF11 gene.


description: Anophthalmia-esophageal atresia syndrome 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.


vesicoureteral reflux 3

description: Any vesicoureteral reflux in which the cause of the disease is a mutation in the SOX17 gene.


psoriatic arthritis, susceptibility to

description: An inherited susceptibility or predisposition to developing psoriatic arthritis.


name: hepatic veno-occlusive disease-immunodeficiency syndrome

description: 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.


primary ciliary dyskinesia 28

description: Any primary ciliary dyskinesia in which the cause of the disease is a mutation in the SPAG1 gene.


myopathy, centronuclear, 5

description: Any autosomal recessive centronuclear myopathy in which the cause of the disease is a mutation in the SPEG gene.


name: spondyloepimetaphyseal dysplasia, Genevieve type

description: 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.


name: developmental and epileptic encephalopathy, 30

description: Any early infantile epileptic encephalopathy in which the cause of the disease is a mutation in the SIK1 gene.


name: Rhabdoid Tumor Predisposition Syndrome 2

description: Rhabdoid tumor predisposition syndrome caused by mutation(s) in the SMARCA4 gene, encoding transcription activator BRG1.


name: intellectual disability, autosomal dominant 16

description: Any Coffin-Siris syndrome in which the cause of the disease is a mutation in the SMARCA4 gene.


name: autoinflammatory syndrome, familial, Behcet-like 1


name: recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome

description: 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.


name: intellectual disability, autosomal recessive 54

description: Any autosomal recessive non-syndromic intellectual disability in which the cause of the disease is a mutation in the TNIK gene.


mucopolysaccharidosis type 3A

description: A rare autosomal recessive lysosomal storage disease caused by deficiency of the enzyme heparan sulfate sulfatase. It is characterized by behavioral changes, sleep disturbances, mental developmental delays and seizures.


name: intellectual disability, autosomal recessive 12


name: developmental and epileptic encephalopathy, 15


Marinesco-Sjogren syndrome

description: Marinesco-Sjogren syndrome (MSS) belongs to the group of autosomal recessive cerebellar ataxias. Cardinal features of MSS are cerebellar ataxia, congenital cataract, and delayed psychomotor development.


holoprosencephaly 2

description: A rare disorder characterized by the partial separation of the cerebral hemispheres. It is associated with mutations in the SIX3 gene.


Christianson syndrome

description: A very rare form of syndromic intellectual deficit characterized by microcephaly, severe developmental delay or regression, hypotonia, abnormal movements, and early-onset seizures.


specific granule deficiency 2

description: Specific granule deficiency-2 is an autosomal recessive immunologic disorder characterized by recurrent infections due to defective neutrophil development. Bone marrow findings include hypercellularity, abnormal megakaryocytes, and features of progressive myelofibrosis with blasts. The disorder is apparent from infancy, and most patients die in early childhood unless they undergo hematopoietic stem cell transplantation. Some patients may have additional findings, including delayed development, mild dysmorphic features, and distal skeletal anomalies (summary by {2:Witzel et al., 2017}).nnFor a discussion of genetic heterogeneity of SGD, see SGD1 (OMIM:245480).


Troyer syndrome

description: Autosomal recessive spastic paraplegia type 20 (SPG20) is a type of complex hereditary spastic paraplegia characterized by an onset in infancy of progressive spastic paraparesis associated with distal amyotrophy, psuedobulbar palsy, motor and cognitive delays, mild cerebellar signs (dysarthria, dysdiadochokinesia, mild intention tremor), short stature and subtle skeletal abnormalities (pes cavus, mild talipes equinovarus, kyphoscoliosis). SPG20 is due to mutations in the SPG20 gene (13q13.1), which encodes the protein spartin.


peeling skin syndrome 5

description: Any peeling skin syndrome in which the cause of the disease is a mutation in the SERPINB8 gene.


pontocerebellar hypoplasia type 2D

description: Any non-syndromic pontocerebellar hypoplasia in which the cause of the disease is a mutation in the SEPSECS gene.


name: intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency


microphthalmia with limb anomalies

description: Microphthalmia with limb anomalies, also known as ophthalmo-acromelic syndrome (OAS), is a rare developmental disorder characterized by bilateral microphthalmia or anophthalmia, synostosis, syndactyly, oligodactyly and/or polydactyly.


name: intellectual disability, anterior maxillary protrusion, and strabismus


Alzheimer disease type 1

description: Alzheimer's disease caused by mutation(s) in the APP gene, encoding amyloid-beta A4 protein. The onset of this condition typically occurs before age 65.


name: intellectual disability, autosomal dominant 27


name: intellectual disability, X-linked, with panhypopituitarism


campomelic dysplasia

description: Campomelic dysplasia is a very rare disorder characterized 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).


Coffin-Siris syndrome 5

description: Any Coffin-Siris syndrome in which the cause of the disease is a mutation in the SMARCE1 gene.


Rotor syndrome

description: Rotor syndrome (RT) is a benign, inherited liver disorder characterized by chronic, predominantly conjugated, nonhemolytic hyperbilirubinemia with normal liver histology.


name: hypertrophic osteoarthropathy, primary, autosomal recessive, 2

description: Any primary hypertrophic osteoarthropathy in which the cause of the disease is a mutation in the SLCO2A1 gene.


name: mitochondrial complex V (ATP synthase) deficiency nuclear type 2

description: A mitochondrial complex deficiency 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.


fibromatosis, gingival, 1

description: Any gingival fibromatosis in which the cause of the disease is a mutation in the SOS1 gene.


Noonan syndrome 4

description: Any Noonan syndrome in which the cause of the disease is a mutation in the SOS1 gene.


osteogenesis imperfecta type 12

description: Any osteogenesis imperfecta in which the cause of the disease is a mutation in the SP7 gene.


name: palmoplantar keratoderma, Nagashima type

description: Keratosis, Nagashima-type is a transgressive and nonprogressive palmoplantar keratoderma resembling a mild form of mal de Meleda.


Leber congenital amaurosis 3

description: Any Leber congenital amaurosis in which the cause of the disease is a mutation in the SPATA7 gene.


Frank-Ter Haar syndrome

description: A syndrome defined by megalocornea, multiple skeletal anomalies, characteristic facial dysmorphism (wide fontanels, prominent forehead, hypertelorism, prominent eyes, full cheeks and micrognathia) and developmental delay.


hereditary spastic paraplegia 11

description: Any hereditary spastic paraplegia in which the cause of the disease is a mutation in the SPG11 gene.


amyotrophic lateral sclerosis type 5

description: Any amyotrophic lateral sclerosis in which the cause of the disease is a mutation in the SPG11 gene.


name: Charcot-Marie-Tooth disease axonal type 2X

description: Any Charcot-Marie-Tooth disease in which the cause of the disease is a mutation in the SPG11 gene.


opsismodysplasia

description: Opsismodysplasia is a skeletal dysplasia characterized by congenital dwarfism and facial dysmorphism.


name: X-linked intellectual disability, Stocco dos Santos type


congenital secretory sodium diarrhea 8

description: Any secretory diarrhea in which the cause of the disease is a mutation in the SLC9A3 gene.


platelet-type bleeding disorder 20

description: Any inherited bleeding disorder, platelet-type in which the cause of the disease is a mutation in the SLFN14 gene.


name: high myopia-sensorineural deafness syndrome

description: 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.


long QT syndrome 12

description: Any long QT syndrome in which the cause of the disease is a mutation in the SNTA1 gene.


CEDNIK syndrome

description: CEDNIK syndrome is a neurocutaneaous syndrome characterized by severe developmental abnormalities of the nervous system and aberrant differentiation of the epidermis.


name: microvascular complications of diabetes, susceptibility to, 6

description: Any microvascular complications of diabetes, susceptibility in which the cause of the disease is a mutation in the SOD2 gene.


sclerosteosis 1

description: Any sclerosteosis in which the cause of the disease is a mutation in the SOST gene.


hyperostosis corticalis generalisata

description: 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.


name: craniodiaphyseal dysplasia, autosomal dominant


Noonan syndrome 9

description: Any Noonan syndrome in which the cause of the disease is a mutation in the SOS2 gene.


cataract 45

description: Any early-onset non-syndromic cataract in which the cause of the disease is a mutation in the SIPA1L3 gene.


spinal muscular atrophy, type 1

description: A severe infantile form of proximal spinal muscular atrophy 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.


spinal muscular atrophy, type II

description: Proximal spinal muscular atrophy type 2 (SMA2) is a chronic infantile form of proximal spinal muscular atrophy 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.


spinal muscular atrophy, type III

description: Proximal spinal muscular atrophy type 3 (SMA3) is a relatively mild form of proximal spinal muscular atrophy 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.


spinal muscular atrophy, type IV

description: Proximal spinal muscular atrophy type 4 (SMA4) is the adult-onset form of proximal spinal muscular atrophy 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.


Curry-Jones syndrome

description: 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.


name: autosomal recessive spinocerebellar ataxia 20

description: Any autosomal recessive cerebellar ataxia in which the cause of the disease is a mutation in the SNX14 gene.


aortic valve disease 2

description: Any aortic valve disease in which the cause of the disease is a mutation in the SMAD6 gene.


craniosynostosis 7

description: Craniosynostosis is a primary abnormality of skull growth involving premature fusion of the cranial sutures such that the growth velocity of the skull often cannot match that of the developing brain. This produces skull deformity and, in some cases, raises intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability (summary by {1:Fitzpatrick, 2013}).nnFor a discussion of genetic heterogeneity of craniosynostosis, see CRS1 (OMIM:123100).


pulmonary hypertension, primary, 2

description: Any primary pulmonary hypertension in which the cause of the disease is a mutation in the SMAD9 gene.


name: isolated growth hormone deficiency type IA

description: An isolated growth hormone deficiency characterized by autosomal recessive inheritance of severe dwarfism with onset by 6 months of age and variable development of antibodies to growth hormone following exogenous supplementation that has material basis in null mutations in the GH1 gene on chromosome 17q23.3.


name: short stature due to growth hormone qualitative anomaly

description: Short stature due to growth hormone qualitative anomaly is characterized by growth retardation and short stature (despite the presence of normal or slightly elevated levels of immunoreactive growth hormone, GH), low concentrations of insulin-like growth factor-I (IGF-I) and a significant increase in growth rate following recombinant GH therapy. Prevalence is unknown but only a few cases have been reported in the literature. The syndrome is caused by various mutations in the GH1 gene (17q22-q24) that result in structural GH anomalies and a biologically inactive molecule. Transmission is autosomal recessive.


name: isolated growth hormone deficiency type II


name: chronic atrial and intestinal dysrhythmia

description: A syndrome characterized by a unique combination of cardiac arrhythmias and intestinal pseudo-obstruction. It has material basis in the mutated SGOL1 protein. Distinctive clinical features include atrial dysrhythmias, sick sinus syndrome (SSS) and valve anomalies and chronic intestinal pseudo-obstruction (CIPO).


Joubert syndrome 20

description: Any Joubert syndrome in which the cause of the disease is a mutation in the TMEM231 gene.


Meckel syndrome, type 11

description: Any Meckel syndrome in which the cause of the disease is a mutation in the TMEM231 gene.


name: corneal dystrophy-perceptive deafness syndrome

description: Corneal dystrophy-perceptive deafness (CDPD) or Harboyan syndrome is a degenerative corneal disorder characterized by the association of congenital hereditary endothelial dystrophy (CHED) with progressive, postlingual sensorineural hearing loss.


name: congenital hereditary endothelial dystrophy of cornea

description: A rare subtype of posterior corneal dystrophy characterized by a diffuse ground-glass appearance of the corneas and marked corneal thickening from birth with nystagmus, and blurred vision.


corneal dystrophy, Fuchs endothelial, 4

description: Any Fuchs' endothelial dystrophy in which the cause of the disease is a mutation in the SLC4A11 gene.


oculocutaneous albinism type 4

description: Oculocutaneous albinism type 4 (OCA4) is a type of OCA characterized by varying degrees of skin and hair hypopigmentation, numerous ocular changes and misrouting of the optic nerves at the chiasm.


Brown-Vialetto-van Laere syndrome 2

description: Any Brown-Vialetto-van Laere syndrome in which the cause of the disease is a mutation in the SLC52A2 gene.


Charlevoix-Saguenay spastic ataxia

description: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neurodegenerative disorder characterized by early-onset cerebellar ataxia with spasticity, a pyramidal syndrome and peripheral neuropathy.


name: keratosis follicularis spinulosa decalvans, X-linked


name: postural orthostatic tachycardia syndrome

description: A condition characterized by development of symptoms while standing. It is an autonomic nervous system disorder and the symptoms are relieved once the person sits back down. Symptoms include heart.


creatine transporter deficiency

description: 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.


name: bronchiectasis with or without elevated sweat chloride 1


name: cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1

description: Any fatal infantile encephalocardiomyopathy in which the cause of the disease is a mutation in the SCO2 gene.


myopia 6

description: Any myopia in which the cause of the disease is a mutation in the SCO2 gene.


osteogenesis imperfecta, type 18

description: Osteogenesis imperfecta type XVIII (OI18) is characterized by congenital bowing of the long bones, wormian bones, blue sclerae, vertebral collapse, and multiple fractures in the first years of life ({1:Doyard et al., 2018}).


name: succinyl-CoA:3-ketoacid CoA transferase deficiency

description: Succinyl-CoA:3-ketoacid CoA transferase deficiency (SCOTD) is a defect in ketone body utilization characterized by severe, potentially fatal intermittent episodes of ketoacidosis.


atrial fibrillation, familial, 14

description: Any familial atrial fibrillation in which the cause of the disease is a mutation in the SCN2B gene.


Brugada syndrome 7

description: Any Brugada syndrome in which the cause of the disease is a mutation in the SCN3B gene.


name: thiamine-responsive megaloblastic anemia syndrome

description: Thiamine-responsive megaloblastic anemia (TRMA) is characterized by a triad of megaloblastic anemia, non-type I diabetes mellitus, and sensorineural deafness.


name: normophosphatemic familial tumoral calcinosis


MIRAGE syndrome

description: An autosomal dominant condition caused by mutation(s) in the SAMD9 gene, encoding sterile alpha motif domain-containing protein 9A. It is a syndromic condition comprising myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital abnormalities, and enteropathy.


name: neuronopathy, distal hereditary motor, type 7A

description: Any neuronopathy, distal hereditary motor in which the cause of the disease is a mutation in the SLC5A7 gene.


congenital myasthenic syndrome 20

description: Any congenital myasthenic syndrome in which the cause of the disease is a mutation in the SLC5A7 gene.


name: hereditary sensory and autonomic neuropathy type 7

description: Hereditary sensory and autonomic neuropathy type 7 (HSAN7) is a genetic condition that causes the inability to feel pain, excessive sweating, and gastrointestinal issues. Gastrointestinal issues can cause failure to thrive, painful constipation, and diarrhea. The constipation is due to intestinal dysmotility, where the the muscles and nerves of the digestive system do not move food through the digestive tract like it should. Signs and symptoms of HSAN7 usually appear at birth or during infancy. The inability to feel pain often leads to repeated, severe injuries, including bone fractures and joint dislocations. People with HSAN7 may also heal slowly putting them at risk for further complications, such as infection. Excessive sweating may cause itching. Other features may include partial insensitivity to cold and hot temperatures, mild muscle weakness, and motor skill delays. HSAN7 is not known to affect learning or intelligence. Treatment of HSAN7 aims to prevent injury and treat gastrointestinal and orthopedic problems. HSAN7 is caused by a mutation in the SCN11A gene. People with HSAN7 have a 1 in 2 or 50% chance of passing the condition on to each of their children. This pattern of inheritance is called ' autosomal dominant.'


name: familial episodic pain syndrome with predominantly lower limb involvement

description: A rare, autosomal dominant disorder caused by mutation in the SCN11A gene. It is characterized by intense episodic pain mainly affecting the distal lower extremities in early childhood. The pain diminishes with age.


name: combined oxidative phosphorylation deficiency 28

description: Any combined oxidative phosphorylation deficiency in which the cause of the disease is a mutation in the SLC25A26 gene.


pontocerebellar hypoplasia type 2B

description: Any non-syndromic pontocerebellar hypoplasia in which the cause of the disease is a mutation in the TSEN2 gene.


name: hypogonadotropic hypogonadism 16 with or without anosmia

description: Any hypogonadotropic hypogonadism in which the cause of the disease is a mutation in the SEMA3A gene.


interstitial lung disease 2

description: A nonneoplastic pulmonary disease that is characterized by the formation of scar tissue within the lungs in the absence of any known cause.


name: respiratory distress syndrome in premature infants

description: 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.


Nager acrofacial dysostosis

description: Nager syndrome, also called Nager acrofacial dysostosis (NAFD) is a congenital malformation syndrome characterized by mandibulofacial dystosis (malar hypoplasia, micrognathia, external ear malformations) and variable preaxial limb defects.


name: autosomal recessive limb-girdle muscular dystrophy type 2E

description: Autosomal recessive limb girdle muscular dystrophy type 2E (LGMD2E) is 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.


myoclonic dystonia 11

description: Any myoclonus-dystonia syndrome in which the cause of the disease is a mutation in the SGCE gene.


name: autosomal recessive limb-girdle muscular dystrophy type 2C

description: Autosomal recessive limb-girdle muscular dystrophy type 2C (LGMD2C) is 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.


atypical glycine encephalopathy

description: Atypical glycine encephalopathy is a rare form of glycine encephalopathy (GE) presenting disease onset or clinical manifestations that differ from neonatal or infantile GE.


familial renal glucosuria

description: Familial Renal Glucosuria (FRG) is characterized by the presence of persistent isolated glucosuria in the absence of both generalized proximal tubular dysfunction and hyperglycemia. FRG is usually considered a benign entity as most patients are not affected by severe clinical consequences. Polyuria and enuresis and later a mild growth and pubertal maturation delay are the only manifestations that have been reported during a follow-up period of 30 years. Episodic dehydration and ketosis during pregnancy and starvation and an increased incidence of urinary tract infections have occasionally been reported in severe cases. FRG is caused by loss-of-function mutations in the gene SLC5A2 (16p11.2).


name: generalized epilepsy with febrile seizures plus, type 1


Brugada syndrome 5

description: Any Brugada syndrome in which the cause of the disease is a mutation in the SCN1B gene.


atrial fibrillation, familial, 13

description: Any familial atrial fibrillation in which the cause of the disease is a mutation in the SCN1B gene.


name: developmental and epileptic encephalopathy, 52


trichothiodystrophy 3, photosensitive

description: An autosomal recessive subtype of trichothiodystrophy caused by mutation(s) in the GTF2H5 gene, encoding general transcription factor IIH subunit 5.


thyroid hormone metabolism, abnormal 1

description: 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.


rigid spine muscular dystrophy 1

description: An inherited muscular dystrophy caused by mutations in the SEPN1 gene. It is characterized by severe limitation in flexion of the dorsolumbar and cervical spine, due to contracture of the spinal extensors. It leads to loss of movement of the spine and the thoracic cage.


PSAT deficiency

description: Phosphoserine aminotransferase deficiency is an extremely rare form of serine deficiency syndrome characterized clinically in the two reported cases to date by acquired microcephaly, psychomotor retardation, intractable seizures and hypertonia.


Neu-Laxova syndrome 2

description: Any Neu-Laxova syndrome in which the cause of the disease is a mutation in the PSAT1 gene.


acute lymphoblastic leukemia

description: Leukemia with an acute onset, characterized by the presence of lymphoblasts in the bone marrow and the peripheral blood. It includes the acute B lymphoblastic leukemia and acute T lymphoblastic leukemia.


name: systemic primary carnitine deficiency disease

description: Systemic primary carnitine deficiency (SPCD) is a potentially lethal disorder of fatty acid oxidation characterized classically by early childhood onset cardiomyopathy often with weakness and hypotonia, failure to thrive and recurrent hypoglycemic hypoketotic seizures and/or coma.


name: SLC35A1-congenital disorder of glycosylation

description: SLC35A1-CDG is an extremely rare form of CDG syndrome characterized clinically in the single reported case by repeated hemorrhagic incidents, including severe pulmonary hemorrhage.


sarcosinemia

description: Sarcosinemia is a metabolic disorder characterized by an increased concentration of sarcosine in plasma and urine due to sarcosine dehydrogenase deficiency.


ulnar-mammary syndrome

description: 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.


Holt-Oram syndrome

description: Holt-Oram syndrome (HOS) is the most common form of heart-hand syndrome and is characterized by skeletal abnormalities of the upper limbs and mild-to-severe congenital cardiac defects.


name: classic dopamine transporter deficiency syndrome

description: Classic Dopamine Transporter Deficiency Syndrome describes a subset of SLC6A3-related DTDS cases which present in early infancy. This disorder is usually first identified by neonatal distress and irritability, feeding difficulties, and motor developmental delay.


name: hyperpigmentation with or without hypopigmentation, familial progressive


name: autosomal dominant nonsyndromic hearing loss 69

description: Any autosomal dominant nonsyndromic deafness in which the cause of the disease is a mutation in the KITLG gene.


cataract 36

description: Any cataract in which the cause of the disease is a mutation in the TDRD7 gene.


name: progressive familial heart block, type 1A

description: An autosomal dominant inherited cardiac bundle branch disorder which can progress to complete heart block.


long QT syndrome 3

description: An autosomal dominant condition caused by mutation(s) in the SCN5A gene, encoding sodium channel protein type 5 subunit alpha. It is characterized by a prolonged QT interval that may result in torsade de pointes, ventricular fibrillation and/or sudden cardiac death.


Brugada syndrome 1

description: Any Brugada syndrome in which the cause of the disease is a mutation in the SCN5A gene.


sick sinus syndrome 1

description: Any sick sinus syndrome in which the cause of the disease is a mutation in the SCN5A gene.


name: ventricular fibrillation, paroxysmal familial, type 1


dilated cardiomyopathy 1E

description: Any familial isolated dilated cardiomyopathy in which the cause of the disease is a mutation in the SCN5A gene.


atrial fibrillation, familial, 10

description: Any familial atrial fibrillation in which the cause of the disease is a mutation in the SCN5A gene.


episodic pain syndrome, familial, 2

description: Any familial episodic pain syndrome in which the cause of the disease is a mutation in the SCN10A gene.


name: epilepsy, familial focal, with variable foci 4


name: developmental and epileptic encephalopathy, 62


action myoclonus-renal failure syndrome

description: Action myoclonus-renal failure syndrome (AMRF) is 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.


Gitelman syndrome

description: Gitelman syndrome (GS), also referred to as familial hypokalemia-hypomagnesemia, is characterized by hypokalemic metabolic alkalosis in combination with significant hypomagnesemia and low urinary calcium excretion.


name: congenital secretory chloride diarrhea 1

description: Any secretory diarrhea in which the cause of the disease is a mutation in the SLC26A3 gene.


Salla disease

description: Salla disease is the mildest form of the free sialic acid storage disorders, which primarily affect the nervous system. Infants with Salla disease typically begin to experience poor muscle tone (hypotonia) during the first year of life,followed by slowly progressive neurological problems. Signs and symptoms include intellectual disability and developmental delay; seizures ; ataxia ; muscle spasticity; and involuntary slow movements of the limbs (athetosis). About one-third of affected children learn to walk. It is caused by mutations in the SLC17A5 gene and is inherited in an autosomal recessive manner. Treatment is generally symptomatic and supportive.


name: free sialic acid storage disease, infantile form


name: porokeratosis 8, disseminated superficial actinic type


acrodermatitis enteropathica

description: Acrodermatitis enteropathica (AE) is a rare inherited inborn error of metabolism resulting in a severe zinc deficiency and characterized by acral dermatitis, alopecia, diarrhea and growth failure.


schneckenbecken dysplasia

description: Schneckenbecken dysplasia (or chondrodysplasia with snail-like pelvis) is a prenatally lethal spondylodysplastic dysplasia.


name: 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency

description: A rare disorder of sex development (DSD) due to a defect in metabolizing testosterone to dihydrotestosterone and characterized by incomplete intrauterine masculinization which ranges from a female genitalia with a blind vaginal pouch to a fully male phenotype with pseudovaginal posterior hypospadias and micropenis.


description: Ehlers-Danlos syndrome, spondylocheirodysplastic type is a subtype of Ehlers-Danlos syndrome characterized by skeletal dysplasia comprising platyspondyly with moderate short stature, osteopenia and widened metaphyses, in addition to hyperextensible, thin, easily bruised skin, hypermobility of small joints with tendency to contractures, prominent eyes with bluish sclerae, wrinkled palms, atrophy of the thenar muscle and tapering fingers.


name: autosomal recessive proximal renal tubular acidosis

description: Autosomal recessive proximal renal tubular acidosis (AR pRTA) is a rare form of proximal renal tubular acidosis (pRTA) 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.


isolated cleft palate

description: A cleft palate that is not part of a larger syndrome.


name: cleft palate with or without ankyloglossia, X-linked

description: 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.


Abruzzo-Erickson syndrome

description: Abruzzo-Erikson syndrome is a multiple congenital anomalies syndrome characterized by a cleft palate, ocular coloboma, hypospadias, mixed conductive-sensorineural hearing loss, short stature, and radio-ulnar synostosis.


name: spastic tetraplegia-thin corpus callosum-progressive postnatal microcephaly syndrome


paragangliomas 2

description: Any paraganglioma in which the cause of the disease is a mutation in the SDHAF2 gene.


pontocerebellar hypoplasia type 2C

description: Any non-syndromic pontocerebellar hypoplasia in which the cause of the disease is a mutation in the TSEN34 gene.


lathosterolosis

description: 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.


polycystic liver disease 2

description: Any polycystic kidney disease in which the cause of the disease is a mutation in the SEC63 gene.


spermatogenic failure 3

description: Any azoospermia in which the cause of the disease is a mutation in the SLC26A8 gene.


name: SLC35A2-congenital disorder of glycosylation

description: SLC35A2-CDG is a 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).


coxopodopatellar syndrome

description: Small patella syndrome (SPS) is a very rare benign bone dysplasia affecting skeletal structures of the lower limb and the pelvis.


Cowden syndrome 7

description: Any Cowden disease in which the cause of the disease is a mutation in the SEC23B gene.


name: congenital dyserythropoietic anemia type 2

description: Congenital dyserythropoietic anemia type II (CDA II) is the most common form of CDA characterized by anemia, jaundice and splenomegaly and often leading to liver iron overload and gallstones.


Cole-Carpenter syndrome 2

description: Any Cole-Carpenter syndrome in which the cause of the disease is a mutation in the SEC24D gene.


primary erythermalgia

description: 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.


name: channelopathy-associated congenital insensitivity to pain, autosomal recessive

description: A syndrome characterized by indifference to pain despite the ability to distinguish noxious from non-noxious stimuli. Absent corneal reflexes and intellectual disability may be associated. Familial forms with autosomal recessive and autosomal dominant patterns of inheritance have been described. (Adams et al., Principles of Neurology, 6th ed, p1343)


paroxysmal extreme pain disorder

description: Paroxysmal extreme pain disorder is a rare disorder of abnormal pain sensation.


name: generalized epilepsy with febrile seizures plus, type 7

description: Any generalized epilepsy with febrile seizures plus in which the cause of the disease is a mutation in the SCN9A gene.


Senior-Loken syndrome 7

description: Any Senior-Loken syndrome in which the cause of the disease is a mutation in the SDCCAG8 gene.


Bardet-Biedl syndrome 16

description: Any Bardet-Biedl syndrome in which the cause of the disease is a mutation in the SDCCAG8 gene.


atrial septal defect 4

description: Any atrial heart septal defect in which the cause of the disease is a mutation in the TBX20 gene.


name: microcephaly 14, primary, autosomal recessive

description: Any autosomal recessive primary microcephaly in which the cause of the disease is a mutation in the SASS6 gene.


spondylocostal dysostosis 5

description: Any spondylocostal dysostosis in which the cause of the disease is a mutation in the TBX6 gene.


glucose-galactose malabsorption

description: 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.


hyperekplexia 3

description: Any hereditary hyperekplexia in which the cause of the disease is a mutation in the SLC6A5 gene.


paramyotonia congenita of Von Eulenburg

description: Paramyotonia congenita of Von Eulenburg is characterized 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).


hyperkalemic periodic paralysis

description: Hyperkalemic periodic paralysis (HyperPP) is a muscle disorder characterized by episodic attacks of muscle weakness associated with an increase in serum potassium concentration.


potassium-aggravated myotonia

description: Potassium-aggravated myotonia (PAM) is a muscular channelopathy presenting with a pure myotonia dramatically aggravated by potassium ingestion, with variable cold sensitivity and no episodic weakness. This group includes three forms: myotonia fluctuans, myotonia permanens, and acetazolamide-responsive myotonia.


congenital myasthenic syndrome 16

description: Any congenital myasthenic syndrome in which the cause of the disease is a mutation in the SCN4A gene.


name: generalized epilepsy with febrile seizures plus, type 2

description: Any febrile seizures, familial in which the cause of the disease is a mutation in the SCN1A gene.


name: developmental and epileptic encephalopathy, 6

description: Any early infantile epileptic encephalopathy in which the cause of the disease is a mutation in the SCN1A gene.


migraine, familial hemiplegic, 3

description: Any familial or sporadic hemiplegic migraine in which the cause of the disease is a mutation in the SCN1A gene.


name: cognitive impairment with or without cerebellar ataxia


name: developmental and epileptic encephalopathy, 13

description: Any early infantile epileptic encephalopathy in which the cause of the disease is a mutation in the SCN8A gene.


seizures, benign familial infantile, 5

description: Any benign familial infantile epilepsy in which the cause of the disease is a mutation in the SCN8A gene.


name: acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome

description: An autosomal recessive cerebellar ataxia that has material basis in homozygous or compound heterozygous mutation in the SCYL1 gene on chromosome 11q13.


name: agenesis of the corpus callosum with peripheral neuropathy

description: Corpus callosum agenesis-neuropathy 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.


ichthyosis prematurity syndrome

description: 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.


paragangliomas 4

description: Any paraganglioma in which the cause of the disease is a mutation in the SDHB gene.


Perrault syndrome 2

description: Any Perrault syndrome in which the cause of the disease is a mutation in the HARS2 gene.


name: frontotemporal dementia and/or amyotrophic lateral sclerosis 4

description: An amyotrophic lateral sclerosis that has material basis in mutation in the TBK1 gene on chromosome 12q14.


name: encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 8


name: fibrosis of extraocular muscles, congenital, 3A, with or without extraocular involvement

description: Any congenital fibrosis of extraocular muscles in which the cause of the disease is a mutation in the TUBB3 gene.


name: complex cortical dysplasia with other brain malformations 1

description: Any complex cortical dysplasia with other brain malformations in which the cause of the disease is a mutation in the TUBB3 gene.


name: hypotonia, infantile, with psychomotor retardation and characteristic facies 3

description: 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.


X-linked dystonia-parkinsonism

description: 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.


name: intellectual disability, X-linked, syndromic 33

description: Any X-linked syndromic intellectual disability in which the cause of the disease is a mutation in the TAF1 gene.


spermatogenic failure 13

description: Any azoospermia in which the cause of the disease is a mutation in the TAF4B gene.


name: diabetes mellitus, noninsulin-dependent, 5

description: Any type 2 diabetes mellitus in which the cause of the disease is a mutation in the TBC1D4 gene.


name: complex cortical dysplasia with other brain malformations 4

description: Any complex cortical dysplasia with other brain malformations in which the cause of the disease is a mutation in the TUBG1 gene.


chordoma

description: Chordomas are rare malignant tumors arising from embryonic remnants of the notochord in axial skeleton.


name: sacral agenesis-abnormal ossification of the vertebral bodies-persistent notochordal canal syndrome


spastic ataxia 3

description: Any autosomal recessive spastic ataxia in which the cause of the disease is a mutation in the MARS2 gene.


name: combined oxidative phosphorylation defect type 25

description: Any combined oxidative phosphorylation deficiency in which the cause of the disease is a mutation in the MARS2 gene.


name: complex cortical dysplasia with other brain malformations 7

description: Any complex cortical dysplasia with other brain malformations in which the cause of the disease is a mutation in the TUBB2B gene.


fetal akinesia deformation sequence 1

description: Any fetal akinesia deformation sequence in which the cause of the disease is a mutation in the MUSK gene.


pontocerebellar hypoplasia type 6

description: Pontocerebellar hypoplasia type 6 (PCH6) is a rare form of pontocerebellar hypoplasia characterized clinically at birth by hypotonia, clonus, epilepsy impaired swallowing and from infancy by progressive microencephaly, spasticity and lactic acidosis.


name: autosomal recessive spinocerebellar ataxia 11

description: Any autosomal recessive syndromic cerebellar ataxia in which the cause of the disease is a mutation in the SYT14 gene.


autosomal dominant Parkinson disease 1

description: An autosomal dominant subtype of Parkinson disease, caused by mutation(s) in the SNCA gene, encoding alpha-synuclein. Mutation(s) in the SNCA gene are responsible for PARK4 and Lewy body dementia, and have overlapping phenotypes.


autosomal dominant Parkinson disease 4

description: A late onset Parkinson disease that has material basis in heterozygous triplication of the alpha-synuclein gene (SNCA) on chromosome 4q22.


Lewy body dementia

description: A progressive form of dementia characterized by the presence of protein deposits called Lewy bodies in the midbrain and cerebral cortex, and loss of cholinergic and dopaminergic neurons. The signs and symptoms overlap with Alzheimer and Parkinson disease.


name: combined oxidative phosphorylation defect type 20

description: Any combined oxidative phosphorylation deficiency in which the cause of the disease is a mutation in the VARS2 gene.


hip dysplasia, Beukes type

description: 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 develops in childhood and that progresses 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.


name: spondyloepimetaphyseal dysplasia, di rocco type


congenital myasthenic syndrome 7

description: Any congenital myasthenic syndrome in which the cause of the disease is a mutation in the SYT2 gene.


name: intellectual disability, autosomal dominant 5

description: Any autosomal dominant non-syndromic intellectual disability in which the cause of the disease is a mutation in the SYNGAP1 gene.


name: growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy

description: A rare, genetic, syndromic intellectual disability disease characterized by severe intrauterine and post-natal growth delay, moderate to severe intellectual disability, and neonatal-onset hepatopathy with fibrosis, steatosis, and/or cholestasis, occasionally leading to liver failure. Additional variable manifestations include muscular hypotonia, zinc deficiency, recurrent infections, diabetes mellitus, joint contractures, skin and joint laxity, hypervitaminosis D, and sensorineural hearing loss.


name: Emery-Dreifuss muscular dystrophy 5, autosomal dominant

description: Any autosomal dominant Emery-Dreifuss muscular dystrophy in which the cause of the disease is a mutation in the SYNE2 gene.


name: epilepsy, X-linked 1, with variable learning disabilities and behavior disorders

description: An epilepsy, X-linked, with or without impaired intellectual development and dysmorphic features characterized by epilepsy, learning difficulties, macrocephaly, and aggressive behavior. 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).


intellectual disability, X-linked 96

description: Any non-syndromic X-linked intellectual disability in which the cause of the disease is a mutation in the SYP gene.


name: Progeroid features, hepatocellular carcinoma predisposition syndrome


spermatogenic failure 6

description: Any azoospermia in which the cause of the disease is a mutation in the SPATA16 gene.


name: neurodevelopmental disorder with hypotonia, neuropathy, and deafness


infantile liver failure syndrome 1

description: Any infantile liver failure in which the cause of the disease is a mutation in the LARS gene.


name: leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome

description: 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.


name: diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome


Gilbert syndrome

description: An autosomal recessive inherited disorder characterized by unconjugated hyperbilirubinemia, resulting in harmless intermittent jaundice.


name: transient familial neonatal hyperbilirubinemia

description: Jaundice in an otherwise healthy breast-fed newborn. It appears four to seven days after birth, lasts longer than the physiologic jaundice, and there are no identifiable causes.


Crigler-Najjar syndrome type 1

description: Crigler-Najjar syndrome type 1 (CNS1) is the most severe form of CNS, a hereditary disorder of hepatic bilirubin conjugation, characterized by severe neonatal unconjugated hyperbilirubinemia due to a complete absence of hepatic bilirubin glucuronosyltransferase (BGT).


Crigler-Najjar syndrome type 2

description: Type 2 Crigler-Najjar syndrome (CNS2) is a hereditary disorder of bilirubin metabolism characterized by unconjugated hyperbilirubinemia due to reduced and inducible activity of hepatic bilirubin glucuronosyltransferase (GT). CNS2 is a milder form of CNS than CNS1.


name: frontotemporal dementia and/or amyotrophic lateral sclerosis 1

description: Any frontotemporal dementia with motor neuron disease in which the cause of the disease is a mutation in the C9orf72 gene.


name: autosomal recessive optic atrophy, OPA7 type


specific language impairment 5

description: A communication disorder that involves the processing of linguistic information.


name: congenital heart defects, multiple types, 2

description: Any congenital heart malformation in which the cause of the disease is a mutation in the TAB2 gene.


gelatinous drop-like corneal dystrophy

description: 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.


name: intellectual disability, autosomal recessive 60


name: microcephaly-thin corpus callosum-intellectual disability syndrome

description: Microcephaly-thin corpus callosum-intellectual disability syndrome is 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.


hypomyelinating leukodystrophy 9

description: Any leukodystrophy in which the cause of the disease is a mutation in the RARS gene.


name: early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome


name: Dyskeratosis Congenita, Autosomal Recessive 3

description: Dyskeratosis congenita caused by autosomal recessive mutation(s) in the WRAP53 gene, encoding telomerase Cajal body protein 1.


hereditary spastic paraplegia 49

description: Any hereditary spastic paraplegia in which the cause of the disease is a mutation in the TECPR2 gene.


autosomal recessive ataxia, Beauce type

description: A rare disorder characterized by a slowly progressive pure cerebellar ataxia associated with dysarthria. It has been described in 53 individuals from 26 families of Canadian origin. The mode of transmission is autosomal recessive. Positional cloning has led to the identification of several gene mutations.


name: Emery-Dreifuss muscular dystrophy 4, autosomal dominant

description: Any autosomal dominant Emery-Dreifuss muscular dystrophy in which the cause of the disease is a mutation in the SYNE1 gene.


Barth syndrome

description: Barth syndrome (BTHS) is an inborn error of phospholipid metabolism characterized by dilated cardiomyopathy (DCM), skeletal myopathy, neutropenia, growth delay and organic aciduria.


torsion dystonia 4

description: DYT4 type primary dystonia is characterized by predominantly laryngeal dystonia (manifesting as whispering dysphonia) and cervical dystonia (manifesting as torticollis).


hypomyelinating leukodystrophy 6

description: A leukodystrophy characterized by slowly progressive spasticity, extrapyramidal movement disorders (dystonia, choreoathetosis and rigidity), cerebellar ataxia, moderate to severe cognitive deficit, and anarthria/dysarthria.


name: complex cortical dysplasia with other brain malformations 6

description: Any complex cortical dysplasia with other brain malformations in which the cause of the disease is a mutation in the TUBB gene.


name: multiple benign circumferential skin creases on limbs 1


description: 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, the latter differs from SSS by its normal intelligence and skeletal features.


name: autosomal recessive Kenny-Caffey syndrome

description: An autosomal recessive form of Kenny-Caffey syndrome due to mutation(s) in the TBCE gene, encoding tubulin-specific chaperone E. This condition is characterized by hypoparathyroidism with hypocalcemia, marked growth retardation, craniofacial anomalies, absent diploic space in the skull, cortical thickening of long bones with medullary stenosis, and small hands and feet.


name: encephalopathy, progressive, with amyotrophy and optic atrophy


transcobalamin II deficiency

description: 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.


name: congenital anomalies of kidney and urinary tract 2

description: Any congenital anomaly of kidney and urinary tract in which the cause of the disease is a mutation in the TBX18 gene.


name: hereditary sensory and autonomic neuropathy with spastic paraplegia

description: This syndrome is characterized by the association of an axonal sensory and autonomic neuropathy with spastic paraplegia.


name: autosomal dominant nonsyndromic hearing loss 12

description: Any autosomal dominant nonsyndromic deafness in which the cause of the disease is a mutation in the TECTA gene.


name: autosomal recessive nonsyndromic hearing loss 21

description: Any autosomal recessive nonsyndromic deafness in which the cause of the disease is a mutation in the TECTA gene.


Werner syndrome

description: 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.


name: combined oxidative phosphorylation defect type 21

description: 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.


name: complex cortical dysplasia with other brain malformations 5

description: Any complex cortical dysplasia with other brain malformations in which the cause of the disease is a mutation in the TUBB2A gene.


name: helicoid peripapillary chorioretinal degeneration

description: 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.


name: autosomal recessive congenital ichthyosis 1

description: Any autosomal recessive congenital ichthyosis in which the cause of the disease is a mutation in the TGM1 gene.


oocyte maturation defect 2

description: Any inherited oocyte maturation defect in which the cause of the disease is a mutation in the TUBB8 gene.


name: developmental and epileptic encephalopathy, 16


name: autosomal dominant nonsyndromic hearing loss 65

description: Any autosomal dominant nonsyndromic deafness in which the cause of the disease is a mutation in the TBC1D24 gene.


DOORS syndrome

description: DOORS syndrome (also known as DOOR syndrome) is a multiple congenital anomalies-intellectual disability syndrome characterized by sensorineural hearing loss (deafness), onychodystrophy, osteodystrophy, mild to profound intellectual disability, and seizures. Isolated seizure disorders and isolated hearing loss have also been reported in individuals as a proposed spectrum of DOORS syndrome.


name: autosomal recessive nonsyndromic hearing loss 86

description: Any autosomal recessive nonsyndromic deafness in which the cause of the disease is a mutation in the TBC1D24 gene.


Warburg micro syndrome 4

description: Any Warburg micro syndrome in which the cause of the disease is a mutation in the TBC1D20 gene.


name: facial palsy, congenital, with ptosis and velopharyngeal dysfunction


Pierpont syndrome

description: 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.


name: intellectual disability, autosomal dominant 41

description: Any autosomal dominant non-syndromic intellectual disability in which the cause of the disease is a mutation in the TBL1XR1 gene.


name: TELO2-related intellectual disability-neurodevelopmental disorder


name: herpes simplex encephalitis, susceptibility to, 4

description: A Mendelian susceptibility or predisposition to herpes simplex infection induced encephalitis in which the cause of the diseas is a mutation in the TICAM1 gene.


name: hereditary motor and sensory neuropathy, Okinawa type

description: 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.


hereditary spastic paraplegia 57

description: An extremely rare, complex type of hereditary spastic paraplegia, characterized by onset in infancy of pronounced leg spasticity (leading to the inability to walk independently), reduced visual acuity due to optic atrophy, and distal wasting of the hands and feet due to an axonal demyelinating sensorimotor neuropathy. SPG57 is caused by mutations in the TFG gene (3q12.2) encoding protein TFG, which is thought to play a role in ER microtubular architecture and function.


Catel-Manzke syndrome

description: 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 comprising micrognathia, cleft palate and glossoptosis.


name: agammaglobulinemia 8, autosomal dominant

description: Any autosomal agammaglobulinemia in which the cause of the disease is a mutation in the TCF3 gene.


amyotrophic lateral sclerosis type 22

description: Any amyotrophic lateral sclerosis in which the cause of the disease is a mutation in the TUBA4A gene.


Joubert syndrome 13

description: Any Joubert syndrome in which the cause of the disease is a mutation in the TCTN1 gene.