name: breasts and/or nipples, aplasia or hypoplasia of, 2

description: Any isolated congenital breast hypoplasia/aplasia in which the cause of the disease is a mutation in the PTPRF gene.


mirror movements 2

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

description: Any familial congenital mirror movements in which the cause of the disease is a mutation in the RAD51 gene.


Fanconi anemia complementation group R

description: Any Fanconi anemia in which the cause of the disease is a mutation in the RAD51 gene.


Noonan syndrome 5

description: Any Noonan syndrome in which the cause of the disease is a mutation in the RAF1 gene.


LEOPARD syndrome 2

description: Any Noonan syndrome with multiple lentigines in which the cause of the disease is a mutation in the RAF1 gene.


dilated cardiomyopathy 1NN

description: Any familial isolated dilated cardiomyopathy in which the cause of the disease is a mutation in the RAF1 gene.


Griscelli syndrome type 2

description: Griscelli syndrome type 2 (GS2) is a rare, inherited condition that affects the skin, hair, and immune system. People with GS2 have unusually light skin and silver-colored hair. They are also prone to recurrent infections and develop an immune condition called hemophagocytic lymphohistiocytosis (HLH). HLH can damage organs and tissues throughout the body, causing life-threatening complications. GS2 is caused by changes (mutations) in the RAB27A gene and is inherited in an autosomal recessive manner. The only current treatment that can extend survival is stem cell transplantation (a bone marrow transplant). Untreated, most children with GS2 do not survive past early childhood.


Smith-McCort dysplasia 2

description: Any Smith-McCort dysplasia in which the cause of the disease is a mutation in the RAB33B gene.


Leber congenital amaurosis 12

description: Any Leber congenital amaurosis in which the cause of the disease is a mutation in the RD3 gene.


name: Hirschsprung disease, susceptibility to, 1

description: An inherited susceptibility or predisposition to developing Hirschsprung disease in which the cause of the disease is a mutation in the RET gene.


multiple endocrine neoplasia type 2A

description: Multiple endocrine neoplasia caused by mutation of the RET gene. Patients develop medullary thyroid carcinomas, and may also develop pheochromocytomas and parathyroid gland hyperplasia.


multiple endocrine neoplasia type 2B

description: Multiple endocrine neoplasia caused by mutation of the RET gene. Patients develop medullary thyroid carcinomas and numerous neural defects including neuromas.


name: mitochondrial complex III deficiency nuclear type 3

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


TARP syndrome

description: A rare developmental defect during embryogenesis syndrome characterized by Robin sequence (micrognathia, glossoptosis, and cleft palate), atrial septal defect, persistence of the left superior vena cava, and talipes equinovarus. The phenotype is variable, some patients present with further dysmorphic characteristics (e.g. hypertelorism, ear abnormalities) while others do not have any key findings. Additional features, such as syndactyly, polydactyly, or brain anomalies (e.g. cerebellar hypoplasia), have also been reported. The syndrome is almost invariably lethal with affected males either dying prenatally or living just a few months.


name: familial acute necrotizing encephalopathy

description: Familial acute necrotizing encephalopathy or ADANE is a potentially fatal neurological disease characterized by neuropathological lesions principally involving the brainstem, thalamus and putamen.


ANE syndrome

description: ANE syndrome is a rare, genetic, neuro-endocrino-cutaneous disorder characterized by highly variable degrees of alopecia, moderate to severe intellectual disability, progressive, late-onset motor deterioration and combined anterior pituitary hormone deficiency, manifesting with central hypogonadotropic hypogonadism, delayed or absent puberty, growth hormone deficiency (resulting in short stature), progressive central adrenal insufficiency and a hypoplastic anterior pituitary gland. Additional features include hypodontia, flexural reticulate hyperpigmentation, gynecomastia, microcephaly and kyphoscoliosis.


hereditary spastic paraplegia 31

description: A rare type of hereditary spastic paraplegia usually characterized by a pure phenotype of proximal weakness of the lower extremities with spastic gait and brisk reflexes, with a bimodal age of onset of either childhood or adulthood (>30 years). In some cases, it can present as a complex phenotype with additional associated manifestations including peripheral neuropathy, bulbar palsy (with dysarthria and dysphagia), distal amyotrophy, and impaired distal vibration sense.


name: neuronopathy, distal hereditary motor, type 5B

description: Any neuronopathy, distal hereditary motor in which the cause of the disease is a mutation in the REEP1 gene.


hereditary spastic paraplegia 72

description: Any pure hereditary spastic paraplegia in which the cause of the disease is a mutation in the REEP2 gene.


Norman-Roberts syndrome

description: Lissencephaly syndrome, Norman-Roberts type is characterized by the association of lissencephaly type I with craniofacial anomalies (severe microcephaly, a low sloping forehead, a broad and prominent nasal bridge and widely set eyes) and postnatal growth retardation.


familial temporal lobe epilepsy 7

description: A temporal lobe epilepsy characterized by autosomal dominant inheritance of focal seizures with prominent auditory symptoms and that has material basis in heterozygous mutation in the RELN gene on chromosome 7q22.


Diamond-Blackfan anemia 6

description: Any Diamond-Blackfan anemia in which the cause of the disease is a mutation in the RPL5 gene.


name: retinitis pigmentosa-juvenile cataract-short stature-intellectual disability syndrome


Hailey-Hailey disease

description: Benign chronic familial pemphigus of Hailey-Hailey is characterized by rhagades mostly located in the armpits, inguinal and perineal folds (scrotum, vulva).


rapadilino syndrome

description: RAPADILINO syndrome is a syndrome for which the acronym indicates the principal signs: RA for radial ray defect, PA for both patellae hypoplasia or aplasia and cleft or highly arched palate, DI for diarrhea and dislocated joints, LI for little size and limb malformations, NO for long, slender nose and normal intelligence.


Baller-Gerold syndrome

description: Baller-Gerold syndrome is characterized by the association of coronal craniosynostosis with radial ray anomalies (oligodactyly, aplasia or hypoplasia of the thumb, aplasia or hypoplasia of the radius).


name: neurodegeneration with brain iron accumulation 7


Warburg micro syndrome 1

description: Any Warburg micro syndrome in which the cause of the disease is a mutation in the RAB3GAP1 gene.


RCBTB1-related retinopathy

description: An autosomal recessive condition caused by mutation(s) in the RCBTB1 gene, encoding RCC1 and BTB domain-containing protein 1. It is characterized by severe retinal dystrophy. Associated extraocular abnormalities may or may not be present.


retinoblastoma

description: A malignant tumor that originates in the nuclear layer of the retina. As the most common primary tumor of the eye in children, retinoblastoma is still relatively uncommon, accounting for only 1% of all malignant tumors in pediatric patients. Approximately 95% of cases are diagnosed before age 5. These tumors may be multifocal, bilateral, congenital, inherited, or acquired. Seventy-five percent of retinoblastomas are unilateral; 60% occur sporadically. A predisposition to retinoblastoma has been associated with 13q14 cytogenetic abnormalities. Patients with the inherited form also appear to be at increased risk for secondary nonocular malignancies such as osteosarcoma, malignant fibrous histiocytoma, and fibrosarcoma.


urinary bladder cancer

description: A primary or metastatic malignant neoplasm involving the bladder.


bone osteosarcoma

description: A usually aggressive malignant bone-forming mesenchymal neoplasm arising from the bone. It may arise de novo or from a pre-existing lesion of the bone. Pain and a palpable mass are the most frequent clinical sign and symptom. It may spread to other anatomic sites, particularly the lungs.


dilated cardiomyopathy 1P

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


hypertrophic cardiomyopathy 18

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


Renpenning syndrome

description: An X-linked syndrome characterized by intellectual deficiency, microcephaly, leanness and mild short stature.


pyruvate carboxylase deficiency disease

description: Pyruvate carboxylase (PC) deficiency is a rare neurometabolic disorder characterized by metabolic acidosis, failure to thrive, developmental delay, and recurrent seizures at an early age in severely affected patients.


name: DDOST-congenital disorder of glycosylation

description: DDOST-CDG is a form of congenital disorders of N-linked glycosylation characterized by failure to thrive, developmental delay, hypotonia, strabismus and hepatic dysfunction. The disease is caused by mutations in the gene DDOST (1p36.1).


nevoid basal cell carcinoma syndrome

description: An autosomal dominant genetic syndrome caused by abnormalities in the PTCH and SUFU gene. It is characterized by multiple basal cell carcinomas at a young age, odontogenic keratocysts, and skeletal defects (bifurcated and splayed ribs, fusion of vertebrae, spinal bifida). Patients with this syndrome may also develop medulloblastomas and ovarian fibromas.


name: basal cell carcinoma, susceptibility to, 1


holoprosencephaly 7

description: Any holoprosencephaly in which the cause of the disease is a mutation in the PTCH1 gene.


Schuurs-Hoeijmakers syndrome

description: Intellectual disability-craniofacial dysmorphism-cryptorchidism syndrome is a rare, genetic, syndromic intellectual disability syndrome characterized by mild to moderate intellectual disability, developmental delay (with speech and language development more severely affected) and facial dysmorphism which typically includes full, arched eyebrows, hypertelorism, down-slanting palpebral fissures, long eyelashes, ptosis, low-set, simple ears, bulbous nasal tip, flat philtrum, wide mouth with downturned corners and thin upper lip and diastema of the teeth. Association with infantile hypotonia, seizures, cryptorchidism in males and congenital abnormalities, including cardiac, cerebral or occular defects, may be observed.


name: congenital plasminogen activator inhibitor type 1 deficiency

description: Congenital plasminogen activator inhibitor type 1 (PAI-1) deficiency is a rare genetic bleeding disorder characterized by premature lysis of hemostatic clots and a moderate bleeding tendency.


spastic ataxia 4

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


description: Pantothenate kinase-associated neurodegeneration (PKAN) is the most common type of neurodegeneration with brain iron accumulation (NBIA), a rare neurodegenerative disorder characterized by progressive extrapyramidal dysfunction (dystonia, rigidity, choreoathetosis), iron accumulation on the brain and axonal spheroids in the central nervous system.


name: hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration


Lenz-Majewski hyperostotic dwarfism

description: Lenz-Majewski hyperostotic dwarfism is an extremely rare syndrome associating dwarfism, characteristic facial appearance, cutis laxa and progressive bone sclerosis.


spinocerebellar ataxia 47

description: A rare hereditary ataxia characterized by adult onset of slowly progressive cerebellar degeneration with gait ataxia, dysmetria, dysarthria, and in some cases diplopia. Cognitive functions are normal, and seizures are absent. Magnetic resonance imaging reveals mild atrophy of the cerebellar vermis.


hypotrichosis 12

description: Any hypotrichosis in which the cause of the disease is a mutation in the RPL21 gene.


name: mitochondrial complex III deficiency nuclear type 5

description: Any mitochondrial complex III deficiency in which the cause of the disease is a mutation in the UQCRC2 gene.


Stankiewicz-Isidor syndrome

description: A neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, behavioral disorders, mild craniofacial anomalies, and variable congenital defects of the cardiac and/or urogenital systems.


nephrotic syndrome, type 6

description: Any nephrotic syndrome in which the cause of the disease is a mutation in the PTPRO gene.


myopathy, distal, 5

description: Any distal myopathy in which the cause of the disease is a mutation in the ADSSL1 gene.


glycogen storage disease VI

description: Liver phosphorylase deficiency, or glycogen storage disease type 6b (Hers' disease, GSD 6b) is a benign and rare form of glycogen storage disease.


paroxysmal nonkinesigenic dyskinesia 1

description: Paroxysmal nonkinesigenic dyskinesia in which the cause of the disease is a mutation in the PNKD gene.


name: short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome

description: Extremely rare primordial dwarfism characterized by short stature, onychodysplasia, facial dysmorphism and hypotrichosis, which is caused by biallelic mutations in the POC1A gene.


name: severe combined immunodeficiency due to DNA-PKcs deficiency

description: Severe combined immunodeficiency (SCID) due to DNA-PKcs deficiency is an extremely rare type of SCID characterized by the classical signs of SCID (severe and recurrent infections, diarrhea, failure to thrive), absence of T and B lymphocytes, and cell sensitivity to ionizing radiation.


name: lethal congenital contracture syndrome 3

description: Lethal congenital contracture syndrome type 3 is a rare arthrogryposis syndrome characterized by clinical features identical to Lethal congenital contracture syndrome type 2 (i.e. multiple congenital contactures (typically extended elbows and flexed knees), micrognathia, anterior horn cells degeneration, skeletal muscle atrophy (mainly in the lower limbs), in the absence of hydrops, pterygia or bone fractures), but without bladder enlargement.


name: microvascular complications of diabetes, susceptibility to, 5

description: Any microvascular complications of diabetes, susceptibility in which the cause of the disease is a mutation in the PON1 gene.


Naxos disease

description: A recessively inherited condition with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) and a cutaneous phenotype, characterized by peculiar wooly hair and palmoplantar keratoderma.


name: arrhythmogenic right ventricular dysplasia 12

description: Any familial isolated arrhythmogenic right ventricular dysplasia in which the cause of the disease is a mutation in the JUP gene.


name: epidermolysis bullosa simplex 5C, with pyloric atresia

description: A basal subtype of epidermolysis bullosa simplex (EBS) characterized by generalized severe blistering with widespread congenital absence of skin and pyloric atresia.


name: epidermolysis bullosa simplex 5B, with muscular dystrophy

description: A basal subtype of epidermolysis bullosa simplex (EBS) characterized by generalized blistering associated with muscular dystrophy.


name: pidermolysis bullosa simplex 5A, Ogna type

description: A basal subtype of epidermolysis bullosa simplex (EBS) characterized by sometimes widespread, primarily acral blistering.


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

description: Autosomal recessive limb-girdle muscular dystrophy type 2Q (LGMD2Q) is a form of limb-girdle muscular dystrophy characterized by proximal muscle weakness presenting in early childhood (with occasional falls and difficulties in climbing stairs) and a progressive course resulting in loss of ambulation in early adulthood. Muscle atrophy and multiple contractures have also been reported in rare cases.


name: epidermolysis bullosa simplex with nail dystrophy


spermatogenic failure 17

description: Any azoospermia in which the cause of the disease is a mutation in the PLCZ1 gene.


hyperprolinemia type 1

description: Hyperprolinaemia type I is an inborn error of proline metabolism characterized by elevated levels of proline in the plasma and urine. The prevalence is unknown. The disorder is generally considered to be benign but associations with renal abnormalities, epileptic seizures, and other neurological manifestations, as well as certain forms of schizophrenia have been reported. It is transmitted as an autosomal recessive trait and is caused by mutations in the proline dehydrogenase or proline oxidase gene (PRODH or POX, 22q11.2).


schizophrenia 4

description: A schizophrenia that has material basis in an autosomal dominant mutation of PRODH on chromosome 22q11.21.


name: thrombophilia due to protein C deficiency, autosomal dominant


name: thrombophilia due to protein C deficiency, autosomal recessive


agnathia-otocephaly complex

description: Agnathia-holoprosencephaly-situs inversus syndrome is an extremely rare and fatal association syndrome, characterized by absence of the mandible, cerebral malformations with facial anomalies related to a defect in cleavage in the embryonic brain (e.g. synophthalmia, malformed and low-set ears fused in midline (otocephaly), agenesis of the olfactory bulbs, microstomia, hypoglossia/aglossia) and situs inversus partialis or totalis.


name: autosomal recessive nonsyndromic hearing loss 84A

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


name: COLORECTAL CANCER, HEREDITARY NONPOLYPOSIS, TYPE 4


Turcot syndrome (disorder)

description: An autosomal dominant hereditary neoplastic syndrome caused by mutations in the PMS2, MLH1, MSH2, or APC genes. There are two types described, type 1, characterized by the presence of glioblastoma and often associated with hereditary nonpolyposis colorectal carcinoma, and type 2, characterized by the presence of medulloblastoma and familiar adenomatous polyposis.


retinitis pigmentosa 13

description: Any retinitis pigmentosa in which the cause of the disease is a mutation in the PRPF8 gene.


name: neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies

description: A rare genetic syndromic intellectual disability characterized by infantile onset of global developmental delay and profound intellectual disability in association with a heterogeneous spectrum of manifestations, such as features of lower motor neuron disease, hypotonia, spasticity, contractures, seizures, respiratory insufficiency, and optic atrophy, among others. Dysmorphic craniofacial features include microcephaly, tall forehead, bitemporal narrowing, flat nasal bridge, low-set ears, and high-arched palate. Brain imaging may show cerebral and cerebellar atrophy, delayed myelination, and thin corpus callosum.


Diamond-Blackfan anemia 7

description: Any Diamond-Blackfan anemia in which the cause of the disease is a mutation in the RPL11 gene.


name: X-linked mixed hearing loss with perilymphatic gusher

description: X-linked mixed deafness with perilymphatic gusher, also known as X-linked deafness type 2, is a rare form of non-syndromic genetic deafnesss affecting males and characterized by pathognomonic inner ear anomalies and conductive and profound sensorineural hearing loss. The inner ear anomalies are described as dilatation of the internal auditory meatus and fistulous connection between the cochlear basal turn and internal auditory canal resulting in perilympatic gusher on attempted mobilization of a fixed stapes. Obligate female carriers may suffer from mild to moderate hearing loss.


xeroderma pigmentosum variant type

description: Xeroderma pigmentosum variant is a milder subtype of xeroderma pigmentosum (XP), a rare genetic photodermatosis characterized by severe sun sensitivity and an increased risk of skin cancer.


neuronal ceroid lipofuscinosis 1

description: A condition associated with mutation(s) in the PPT1 gene, encoding palmitoyl-protein thioesterase 1. The condition is one of a group of genetically heterogeneous neurodegenerative disorders, characterized by accumulation of intracellular lipopigments.


name: proteasome-associated autoinflammatory syndrome 1

description: An autosomal recessive condition caused by mutation(s) in the PSMB8 gene, encoding proteasome subunit beta type-8. It is characterized by early onset annular erythematous plaques, partial lipodystrophy, and recurrent fever.


retinitis pigmentosa 60

description: Any retinitis pigmentosa in which the cause of the disease is a mutation in the PRPF6 gene.


name: pyogenic arthritis-pyoderma gangrenosum-acne syndrome

description: A rare pleiotropic autoinflammatory disorder of childhood, primarily affecting the joints and skin.


left ventricular noncompaction 8

description: Any familial isolated dilated cardiomyopathy in which the cause of the disease is a mutation in the PRDM16 gene.


name: congenital insensitivity to pain-hypohidrosis syndrome

description: A hereditary sensory neuropathy characterized by congenital insensitivity to pain and decreased sweating and tear production that has material basis in homozygous mutation in the PRDM12 gene on chromosome 9q34.


name: autosomal recessive juvenile Parkinson disease 2

description: A group of disorders which feature impaired motor control characterized by bradykinesia, muscle rigidity; tremor; and postural instability. Parkinsonian diseases are generally divided into primary parkinsonism (see parkinson disease), secondary parkinsonism (see parkinson disease, secondary) and inherited forms. These conditions are associated with dysfunction of dopaminergic or closely related motor integration neuronal pathways in the basal ganglia.


name: lymphedema-posterior choanal atresia syndrome


type 1 diabetes mellitus

description: A chronic condition characterized by minimal or absent production of insulin by the pancreas.


rheumatoid arthritis

description: A chronic, systemic autoimmune disorder characterized by inflammation in the synovial membranes and articular surfaces. It manifests primarily as a symmetric, erosive polyarthritis that spares the axial skeleton and is typically associated with the presence in the serum of rheumatoid factor.


name: vitiligo-associated multiple autoimmune disease susceptibility 6


immunodeficiency 104

description: A severe combined immunodeficiency characterized by being T cell-negative, B cell-positive and natural killer cell-positive and that has material basis in homozygous or compound heterozygous mutation in the IL7R gene on chromosome 5p13 or the CD45 gene on chromosome 1q31.


name: intellectual developmental disorder with gastrointestinal difficulties and high pain threshold

description: IDDGIP is an autosomal dominant syndromic neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability with speech delay, and behavioral abnormalities. Most patients have variable additional features, including feeding and gastrointestinal difficulties, high pain threshold and/or hypersensitivity to sound, and dysmorphic features, including mild facial abnormalities, strabismus, and small hands and feet (summary by {1:Jansen et al., 2017}).


Oguchi disease-2

description: Any Oguchi disease in which the cause of the disease is a mutation in the GRK1 gene.


amyotrophic lateral sclerosis type 18

description: Any amyotrophic lateral sclerosis in which the cause of the disease is a mutation in the PFN1 gene.


properdin deficiency, X-linked

description: A rare, hereditary, primary immunodeficiency due to a complement cascade protein anomaly characterized by significantly increased susceptibility to Neisseria species infections. It only affects males, typically presenting with severe or fulminant meningococcal disease.


name: thrombophilia due to protein S deficiency, autosomal dominant

description: Autosomal dominant form of hereditary thrombophilia due to congenital protein S deficiency.


name: thrombophilia due to protein S deficiency, autosomal recessive


retinitis pigmentosa 7

description: A retinitis pigmentosa that has material basis in mutation in the PRPH2 gene on chromosome 6p21.


fundus albipunctatus

description: Fundus albipunctatus is a rare, genetic retinal dystrophy characterized by the presence of numerous small, round, yellowish-white retinal lesions that are distributed throughout the retina but spare the fovea. Patients present in childhood with non-progressive night blindness with prolonged cone and rod adaptation times. The macula may or may not be involved, which may result in a decrease of central visual acuity with age.


vitelliform macular dystrophy 3

description: Any vitelliform macular dystrophy in which the cause of the disease is a mutation in the PRPH2 gene.


patterned macular dystrophy 1

description: Any patterned macular dystrophy in which the cause of the disease is a mutation in the PRPH2 gene.


choroidal dystrophy, central areolar 2

description: Any central areolar choroidal dystrophy in which the cause of the disease is a mutation in the PRPH2 gene.


retinitis pigmentosa 70

description: Any retinitis pigmentosa in which the cause of the disease is a mutation in the PRPF4 gene.


retinitis pigmentosa 18

description: Any retinitis pigmentosa in which the cause of the disease is a mutation in the PRPF3 gene.


variegate porphyria

description: Variegate porphyria is a form of acute hepatic porphyria characterized by the occurrence of neuro-visceral attacks with or without the presence of cutaneous lesions.


Charcot-Marie-Tooth disease type 4F

description: Charcot-Marie-Tooth disease type 4F (CMT4F) is a severe, demyelinating subtype of Charcot-Marie-Tooth disease type 4 characterized by the childhood onset of a slowly-progressing typical CMT phenotype (i.e. distal muscle weakness and atrophy, as well as pes cavus) that presents severe sensory loss (frequently with sensory ataxia), moderately to severely reduced motor nerve conduction velocities and almost invariable absence of sensory nerve action potentials, and delayed motor milestones.


brittle cornea syndrome 2

description: Any brittle cornea syndrome in which the cause of the disease is a mutation in the PRDM5 gene.


name: microcephaly, short stature, and impaired glucose metabolism 2

description: Any microcephaly, short stature, and impaired glucose metabolism in which the cause of the disease is a mutation in the PPP1R15B gene.


epilepsy, progressive myoclonic, 1B

description: Any progressive myoclonic epilepsy in which the cause of the disease is a mutation in the PRICKLE1 gene.


inherited Creutzfeldt-Jakob disease

description: Inherited or familial Creutzfeldt-Jakob disease (fCJD) is a very rare form of genetic prion disease characterized by typical CJD features (rapidly progressive dementia, personality/behavioral changes, psychiatric disorders, myoclonus, and ataxia) with a genetic cause and sometimes a family history of dementia.


fatal familial insomnia

description: Fatal familial insomnia (FFI) is a very rare form of prion disease characterized by subacute onset of insomnia showing as a reduced overall sleep time, autonomic dysfunction, and motor disturbances.


Gerstmann-Straussler-Scheinker syndrome

description: A very rare and fatal disorder of spongiform encephalopathy usually caused by mutations of the prion protein (PRNP) gene. It is characterized by the accumulation of amyloid in the brain. Signs and symptoms include lack of motor coordination, unsteady gait, and difficulty walking. As the disease progresses, patients develop speech difficulties and dementia.


Huntington disease-like 1

description: Any neurodegenerative disease with chorea in which the cause of the disease is a mutation in the PRNP gene.


name: spongiform encephalopathy with neuropsychiatric features


dystonia 16

description: Dystonia 16 (DYT16) is a very rare and newly discovered movement disorder which is characterized by early-onset progressive limb dystonia, laryngeal and oromandibular dystonia, and parkinsonism.


name: hypogonadotropic hypogonadism 4 with or without anosmia

description: Any hypogonadotropic hypogonadism in which the cause of the disease is a mutation in the PROK2 gene.


retinitis pigmentosa 41

description: Any retinitis pigmentosa in which the cause of the disease is a mutation in the PROM1 gene.


cone-rod dystrophy 12

description: Any cone-rod dystrophy in which the cause of the disease is a mutation in the PROM1 gene.


Stargardt disease 4

description: Any Stargardt disease in which the cause of the disease is a mutation in the PROM1 gene.


retinal macular dystrophy type 2

description: Retinal macular dystrophy type 2 is a rare, genetic macular dystrophy disorder characterized by slowly progressive ''bull's eye'' maculopathy associated, in most cases, with mild decrease in visual acuity and central scotomata. Usually, only the central retina is involved, however some cases of more widespread rod and cone anomalies have been reported. Rare additional features include empty sella turcica, impaired olfaction, renal infections, hematuria and recurrent miscarriages.


name: pituitary hormone deficiency, combined, 2

description: Any combined pituitary hormone deficiencies, genetic form in which the cause of the disease is a mutation in the PROP1 gene.


name: intellectual disability, X-linked, syndromic, 35


retinitis pigmentosa 11

description: Any retinitis pigmentosa in which the cause of the disease is a mutation in the PRPF31 gene.


description: Phosphoribosylpyrophosphate (PRPP) synthetase superactivity is an X-linked disorder of purine metabolism associated with hyperuricemia and hyperuricosuria, comprised of two forms: an early-onset severe form characterized by gout, urolithiasis, and neurodevelopmental anomalies (severe PRPP synthetase superactivity) and a mild late-onset form with no neurologic involvement (mild PRPP synthetase superactivity).


name: Charcot-Marie-Tooth disease X-linked recessive 5

description: X-linked Charcot-Marie-Tooth disease type 5 is a rare, genetic, peripheral sensorimotor neuropathy characterized by an X-linked recessive inheritance pattern and the infancy- to childhood-onset of: 1) progressive distal muscle weakness and atrophy (first appearing and more prominent in the lower extremities than the upper) which usually manifests with foot drop and gait disturbance, 2) bilateral, profound, prelingual sensorineural hearing loss and 3) progressive optic neuropathy. Females are asymptomatic and do not display the phenotype.


Arts syndrome

description: Lethal ataxia with deafness and optic atrophy (also known as Arts syndrome) is characterized by intellectual deficit, early-onset hypotonia, ataxia, delayed motor development, hearing impairment and loss of vision due to optic atrophy.


episodic kinesigenic dyskinesia 1

description: An autosomal dominant condition caused by mutation(s) in the PRRT2 gene, encoding proline-rich transmembrane protein 2. It is characterized by dyskinesia triggered by sudden movement. It shares features with infantile convulsions and paroxysmal choreoathetosis, familial. It is an allelic disorder.


name: infantile convulsions and choreoathetosis

description: A neurological condition characterized by the occurrence of seizures during the first year of life (Benign familial infantile epilepsy) and choreoathetotic dyskinetic attacks during childhood or adolescence.


isolated microphthalmia 6

description: Any isolated microphthalmia in which the cause of the disease is a mutation in the PRSS56 gene.


spermatogenic failure 16

description: Any azoospermia in which the cause of the disease is a mutation in the SUN5 gene.


isolated sulfite oxidase deficiency

description: Abnormally reduced sulfite oxidase level.


cleidocranial dysplasia 1

description: A condition that primarily affects the development of the bones and teeth. Characteristic features include underdeveloped or absent collarbones (clavicles); dental abnormalities; and delayed closing of the spaces between the skull bones (fontanels). Other features may include decreased bone density (osteopenia), osteoporosis, hearing loss, bone abnormalities of the hands, and recurrent sinus and ear infections. CCD is caused by changes (mutations) in the RUNX2 gene and inheritance is autosomal dominant. It may be inherited from an affected parent or occur due to a new mutation in the RUNX2 gene. Management may include dental procedures, treatment of sinus and ear infections, use of helmets for high-risk activities, and/or surgery for skeletal problems.


name: metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome

description: Metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome is characterized by metaphyseal dysplasia associated with short stature and facial dysmorphism (a beaked nose, short philtrum, thin lips, maxillary hypoplasia, dystrophic yellowish teeth) and acral anomalies (short fifth metacarpals and/or short middle phalanges of fingers two and five). It has been described in several members spanning four generations of a French-Canadian family. The syndrome is likely to be transmitted as an autosomal dominant trait.


hypotrichosis 11

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


name: developmental and epileptic encephalopathy, 34

description: Any early infantile epileptic encephalopathy in which the cause of the disease is a mutation in the SLC12A5 gene.


name: epilepsy, idiopathic generalized, susceptibility to, 14


name: autism spectrum disorder - epilepsy - arthrogryposis syndrome

description: SLC35A3-CDG is a form of congenital disorders of N-linked glycosylation characterized by distal arthrogryposis (mild flexion contractures of the fingers, deviation of the distal phalanges, swan-neck deformity), retromicrognathia, general muscle hypotonia, delayed psychomotor development, autism spectrum disorder (speech delay, abnormal use of speech, difficulties in initiating, understanding and maintaining social interaction, limited non-verbal communication and repetitive behavior), seizures, microcephaly and mild to moderate intellectual disability that becomes apparent with age. The disease is caused by mutations in the gene SLC35A3 (1p21).


long QT syndrome 10

description: Any long QT syndrome in which the cause of the disease is a mutation in the SCN4B gene.


spermatogenic failure, X-linked, 2

description: Any azoospermia in which the cause of the disease is a mutation in the TEX11 gene.


name: combined oxidative phosphorylation deficiency 32


name: malignant hyperthermia, susceptibility to, 1

description: Any malignant hyperthermia of anesthesia in which the cause of the disease is a mutation in the RYR1 gene.


central core myopathy

description: An autosomal dominant congenital disorder affecting the skeletal muscles. Microscopically, it is characterized by disorganized areas, which are called cores, seen usually in the center of the muscle fibers. Clinically it presents as mild to severe muscle weakness. It may be associated with skeletal abnormalities including scoliosis, joint deformities, and hip dislocation.


name: congenital multicore myopathy with external ophthalmoplegia

description: An autosomal recessive condition caused by mutation(s) in the RYR1 gene, encoding ryanodine receptor 1. It may be characterized clinically by neonatal hypotonia, delayed motor development, and generalized muscle weakness, and amyotrophy. Pathologically, the absence of mitochondria and focal disorganization of the sarcomere appear as "minicores" on ATPase staining as a result of focal defects in oxidative activity.


H syndrome

description: A systemic inherited histiocytosis, with characteristic cutaneous findings accompanying systemic manifestations. H syndrome refers to the major clinical findings of hyperpigmentation, hypertrichosis, hepatosplenomegaly, heart anomalies, hearing loss, hypogonadism, low height, and occasionally, hyperglycemia/diabetes mellitus. Due to overlapping clinical features, H syndrome is now considered to include pigmented hypertrichosis with insulin dependent diabetes mellitus syndrome (PHID), Faisalabad histiocytosis (FHC) and familial sinus histiocytosis with massive lymphadenopathy (FSHML).


hypermanganesemia with dystonia 2

description: Any hypermanganesemia with dystonia in which the cause of the disease is a mutation in the SLC39A14 gene.


hyperostosis cranialis interna

description: Bony overgrowth of the internal (endosteal) surface of the calvaria and the base of skull.


hemochromatosis type 4

description: A form of rare hemochromatosis (HC) characterized by increased transferrin saturation and hepatocellular iron deposition with distribution patterns and clinical features indistinguishable from patients with other types of HC.


Brown-Vialetto-van Laere syndrome 1

description: Any Brown-Vialetto-van Laere syndrome in which the cause of the disease is a mutation in the SLC52A3 gene.


progressive bulbar palsy of childhood

description: A progressive bulbar palsy of childhood that occurs during childhood.


ataxia-pancytopenia syndrome

description: A rare genetic disease characterized by cerebellar ataxia, cytopenias and predisposition to bone marrow failure and myeloid leukemia. Neurologic features variably include slowly progressive cerebellar ataxia or balance impairment with cerebellar atrophy and periventricular white matter T2 hyperintensities in brain MRI, horizontal and vertical nystagmus, dysmetria, dysarthria, pyramidal tract signs and reduced nerve conduction velocity. Hematological abnormalities are variable and may be intermittent and include cytopenias of all cell lineages, immunodeficiency, myelodysplasia and acute myeloid leukemia.


name: asthma, nasal polyps, and aspirin intolerance


Fontaine progeroid syndrome

description: A rare premature aging syndrome characterized by pre-and postnatal growth retardation, a congenital premature-aged appearance with distinctive craniofacial dysmorphism (wide calvaria with large open anterior fontanel and wide metopic suture, broad forehead, small face, micrognathia), markedly diminished subcutaneous fat, cutis laxa and wrinkled skin, without delay in psychomotor development. Scant, brittle hair, hypoplastic nails and delayed, abnormal dentition, as well as hypoplastic distal phalanges, umbilical hernia and eye abnormalities (myopia/hyperopia, strabismus), are also commonly associated.


name: autosomal recessive pseudohypoaldosteronism type 1

description: Generalized pseudohypoaldosteronism type 1 (generalized PHA1) is a severe form of primary mineralocorticoid resistance with systemic involvement and salt loss in multiple organs.


name: bronchiectasis with or without elevated sweat chloride 2

description: Any bronchiectasis in which the cause of the disease is a mutation in the SCNN1A gene.


acquired polycythemia vera

description: Polycythemia vera (PV) is an acquired myeloproliferative disorder characterized by an elevated absolute red blood cell mass caused by uncontrolled red blood cell production, frequently associated with uncontrolled white blood cell and platelet production.


myelodysplastic syndrome

description: A clonal hematopoietic disorder characterized by dysplasia and ineffective hematopoiesis in one or more of the hematopoietic cell lines. The dysplasia may be accompanied by an increase in myeloblasts, but the number is less than 20%, which, according to the WHO guidelines, is the requisite threshold for the diagnosis of acute myeloid leukemia. It may occur de novo or as a result of exposure to alkylating agents and/or radiotherapy. (WHO, 2001)


Liddle syndrome 1

description: Any Liddle syndrome in which the cause of the disease is a mutation in the SCNN1B gene.


name: bronchiectasis with or without elevated sweat chloride 3

description: Any bronchiectasis in which the cause of the disease is a mutation in the SCNN1G gene.


seizures, benign familial infantile, 3

description: Any benign familial infantile epilepsy in which the cause of the disease is a mutation in the SCN2A gene.


name: developmental and epileptic encephalopathy, 11

description: Any early infantile epileptic encephalopathy in which the cause of the disease is a mutation in the SCN2A gene.


Pendred syndrome

description: Pendred syndrome (PDS) is a clinically variable genetic disorder characterized by bilateral sensorineural hearing loss and euthyroid goiter.


name: autosomal recessive nonsyndromic hearing loss 4

description: An autosomal recessive nonsyndromic deafness that has material basis in mutation in the SLC26A4 gene on chromosome 7q22. Mutation in the FOXI1 gene has been found to be a rare cause of EVA. EVA may also be rarely caused by digenic inheritance of heterozygous mutations in the SLC26A4 and FOXI1 genes, or in the SLC26A4 and KCNJ10 genes.


name: autosomal recessive nonsyndromic hearing loss 61

description: Any autosomal recessive nonsyndromic deafness in which the cause of the disease is a mutation in the SLC26A5 gene.


retinitis pigmentosa 68

description: Any retinitis pigmentosa in which the cause of the disease is a mutation in the SLC7A14 gene.


hyperglycinuria

description: An increased concentration of glycine in the urine.


iminoglycinuria

description: A metabolic disorder resulting from defective renal tube reabsorption of proline, hydroxyproline and glycine. The prevalence is estimated at around 1 in 15 000. The disorder is usually asymptomatic and is identified fortuitously by detection of increased levels of the imino acids and glycine in the urine. It is transmitted as an autosomal recessive trait.


Duane-radial ray syndrome

description: A syndrome of multiple congenital anomalies and is characterized by ocular manifestations (uni- or bilateral Duane anomaly (95% of cases), congenital optic nerve hypoplasia or optic disk coloboma), bilateral deafness and radial ray malformation that can include thenar hypoplasia and/or hypoplasia or aplasia of the thumbs; hypoplasia or aplasia of the radii; shortening and radial deviation of the forearms; triphalangeal thumbs; and duplication of the thumb (preaxial polydactyly).The phenotype overlaps with other SALL4>/i> related disorders including acro-renal-ocular syndrome and Holt-Oram syndrome (see these terms). Transmission is autosomal dominant.


IVIC syndrome

description: IVIC syndrome is a very rare genetic malformation syndrome characterized by upper limb anomalies (radial ray defects, carpal bone fusion), extraocular motor disturbances, and congenital bilateral non-progressive mixed hearing loss.


Tay-Sachs disease AB variant

description: GM2 gangliosidosis, AB variant is an extremely rare, severe genetic disorder characterized by progressive neurological decline due to ganglioside activator deficiency.


Aicardi-Goutieres syndrome 5

description: Any Aicardi-Goutieres syndrome in which the cause of the disease is a mutation in the SAMHD1 gene.


chilblain lupus 2

description: Any chilblain lupus in which the cause of the disease is a mutation in the SAMHD1 gene.


combined PSAP deficiency

description: Encephalopathy due to prosaposin deficiency is a lysosomal storage disease belonging to the group of sphingolipidoses.


name: metachromatic leukodystrophy due to saposin B deficiency


name: Gaucher disease due to saposin C deficiency

description: Any Gaucher disease in which the cause of the disease is a mutation in the PSAP gene.


name: Krabbe disease due to saposin A deficiency


craniolenticulosutural dysplasia

description: Craniolenticulosutural dysplasia (CLSD), also known as Boyadjiev-Jabs syndrome, is characterized by the specific association of large and late-closing fontanels, hypertelorism, early-onset cataract and mild generalized skeletal dysplasia.


name: microcephalic primordial dwarfism due to RTTN deficiency

description: Microcephalic primordial dwarfism due to RTTN deficiency is a rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by primary microcephaly, profound short stature, moderate to severe intellectual disability, global developmental delay, craniofacial dysmorphism (e.g. sloping forehead, high and broad nasal bridge) and variable brain malformations, including simplified gyration, pachygyria, polymicrogyria, reduced sulcation, dysgenesis of corpus callosum and deformed ventricles. Renal anomalies, bilateral hearing loss, multiple joint contractures, severe failure to thrive and a sacral lesion cephalad to the gluteal crease have also been reported.


name: muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 10

description: Any muscular dystrophy-dystroglycanopathy, type A in which the cause of the disease is a mutation in the RXYLT1 gene.


name: foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome


Charcot-Marie-Tooth disease type 4C

description: Charcot-Marie-Tooth disease type 4C (CMT4C) is a subtype of Charcot-Marie-Tooth type 4 characterized by childhood or adolescent-onset of a relatively mild, demyelinating sensorimotor neuropathy that contrasts with a severe, rapidly progressing, early-onset scoliosis, and the typical CMT phenotype (i.e. distal muscle weakness and atrophy, sensory loss, and often foot deformity). A wide spectrum of nerve conduction velocities are observed and cranial nerve involvement and kyphoscoliosis have also been reported.


name: susceptibility to mononeuropathy of the median nerve, mild


name: hyperuricemic nephropathy, familial juvenile type 4

description: Any familial juvenile hyperuricemic nephropathy in which the cause of the disease is a mutation in the SEC61A1 gene.


name: macrothrombocytopenia, isolated, 1, autosomal dominant

description: Any autosomal dominant macrothrombocytopenia in which the cause of the disease is a mutation in the TUBB1 gene.


DiGeorge syndrome

description: A congenital anomaly characterized by immunodeficiency, abnormal facies, congenital heart disease, hypocalcemia, and increased susceptibility to infections. Pathologic characteristics include conotruncal abnormalities and absence or hypoplasia of thymus and parathyroid glands. DiGeorge syndrome is associated with abnormalities of chromosome 22. Also known as DiGeorge anomaly.


velocardiofacial syndrome

description: A chromosomal disease that has material basis in deletion polymorphisms at chromosome location 22q11 and is characterized by variable developmental problems and schizoid features.


conotruncal heart malformations

description: Conotruncal heart malformations are a group of congenital cardiac outflow tract anomalies that include such defects as tetralogy of Fallot, pulmonary atresia with ventricular septal defect, double-outlet right ventricle (DORV), double-outlet left ventricle, truncus arteriosus and transposition of the great arteries (TGA), among others. This group of defects is frequently found in patients with 22q11.2 deletion syndrome. A deletion of chromosome 22q11.2 has equally been associated in a subset of patients with various types of isolated non-syndromic conotruncal heart malformations (with the exception of DORV and TGA where this is very uncommon).


cerebrocostomandibular syndrome

description: Cerebro-costo-mandibular syndrome (CCMS) is characterized at birth by posterior rib gaps and orofacial anomalies reminiscent of Pierre Robin syndrome that include palatal defects (short hard palate, absent soft palate, absent uvula), micrognathia and glossoptosis.


name: intellectual disability, autosomal recessive 61

description: An autosomal recessive non-syndromic intellectual disability that has material basis in an autosomal recessive mutation of the RUSC2 gene on chromosome 9p13.


isolated microphthalmia 3

description: Any isolated microphthalmia in which the cause of the disease is a mutation in the RAX gene.


Hartnup disease

description: Hartnup disease is a rare metabolic disorder belonging to the neutral aminoacidurias and characterized by abnormal renal and gastrointestinal transport of neutral amino acids (tryptophan, alanine, asparagine, glutamine, histidine, isoleucine, leucine, phenylalanine, serine, threonine, tyrosine and valine).


ariboflavinosis

description: A dietary deficiency of riboflavin causing a syndrome chiefly marked by cheilitis, angular stomatitis, glossitis associated with a purplish red or magenta-colored tongue that may show fissures, corneal vascularization, dyssebacia, and anemia. (Dorland, 27th ed)


name: hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase

description: Psychomotor retardation due to S-adenosylhomocysteine hydrolase deficiency is characterized by psychomotor delay and severe myopathy (hypotonia, absent tendon reflexes and delayed myelination) from birth, associated with hypermethioninaemia and elevated serum creatine kinase levels.


chylomicron retention disease

description: Chylomicron retention disease (CRD) is a type of familial hypocholesterolemia characterized by malnutrition, failure to thrive, growth failure, vitamin E deficiency and hepatic, neurologic and ophthalmologic complications.


name: palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome

description: Palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome is characterized by sex reversal in males with a 46, XX (SRY-negative) karyotype, palmoplantar hyperkeratosis and a predisposition to squamous cell carcinoma. To date, five cases (four of whom were brothers) have been described. The etiology is unknown.


cryptorchidism

description: The failure of one or both testes of a male fetus to descend from the abdomen into the scrotum during the late part of pregnancy. If not surgically corrected in early childhood, males may be at increased risk for testicular cancer later in life.


name: catecholaminergic polymorphic ventricular tachycardia 1

description: Polymorphic ventricular tachycardia induced by adrenergic stress. It is inherited in an autosomal dominant pattern and is caused by mutations in the ryanodine receptor 2 (RYR2) gene.


name: Platelet Disorder, Familial, with Associated Myeloid Malignancy

description: An autosomal dominant condition caused by mutation(s) in the RUNX1 gene, encoding runt-related transcription factor 1. It is characterized by thrombocytopenia, abnormal platelet function, and a propensity to develop acute myeloid leukemia.


name: autosomal recessive nonsyndromic hearing loss 68

description: Any autosomal recessive nonsyndromic deafness in which the cause of the disease is a mutation in the S1PR2 gene.


embryonal rhabdomyosarcoma

description: A poorly circumscribed morphologic variant of rhabdomyosarcoma. It is characterized by the presence of primitive skeletal muscle differentiation in any stage of myogenesis.


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

description: Any hereditary motor and sensory neuropathy type 6 in which the cause of the disease is a mutation in the SLC25A46 gene.


name: intellectual developmental disorder with neuropsychiatric features

description: Intellectual developmental disorder with neuropsychiatric features is an autosomal recessive disorder characterized by moderate intellectual disability, relatively mild seizures, and neuropsychiatric abnormalities, such as anxiety, obsessive-compulsive behavior, and autistic features. Mild facial dysmorphic features may also be present (summary by {2:Srour et al., 2017}).


name: progressive essential tremor-speech impairment-facial dysmorphism-intellectual disability-abnormal behavior syndrome


name: autosomal dominant aplasia and myelodysplasia


name: rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked


name: hypogonadotropic hypogonadism 17 with or without anosmia

description: Any hypogonadotropic hypogonadism in which the cause of the disease is a mutation in the SPRY4 gene.


Diamond-Blackfan anemia 4

description: Any Diamond-Blackfan anemia in which the cause of the disease is a mutation in the RPS17 gene.


name: arhinia, choanal atresia, and microphthalmia


name: combined oxidative phosphorylation defect type 8

description: Combined oxidative phosphorylation defect type 8 is a mitochondrial disease due to a defect in mitochondrial protein synthesis resulting in deficiency of respiratory chain complexes I, III and IV in the cardiac and skeletal muscle and brain characterized by severe hypertrophic cardiomyopathy, pulmonary hypoplasia, generalized muscle weakness and neurological involvement.


name: leukoencephalopathy, progressive, with ovarian failure


name: frontotemporal dementia and/or amyotrophic lateral sclerosis 3

description: An amyotrophic lateral sclerosis that has material basis in mutation in the SQSTM1 gene on chromosome 5q35.


name: neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset


congenital secretory sodium diarrhea 3

description: Any secretory diarrhea in which the cause of the disease is a mutation in the SPINT2 gene.


Diamond-Blackfan anemia 8

description: Any Diamond-Blackfan anemia in which the cause of the disease is a mutation in the RPS7 gene.


primary ciliary dyskinesia 11

description: Any primary ciliary dyskinesia in which the cause of the disease is a mutation in the RSPH4A gene.


Leber congenital amaurosis 6

description: Any Leber congenital amaurosis in which the cause of the disease is a mutation in the RPGRIP1 gene.


cone-rod dystrophy 13

description: Any cone-rod dystrophy in which the cause of the disease is a mutation in the RPGRIP1 gene.


retinitis pigmentosa 9

description: Any retinitis pigmentosa in which the cause of the disease is a mutation in the RP9 gene.


Cornelia de Lange syndrome 3

description: Any Cornelia de Lange syndrome in which the cause of the disease is a mutation in the SMC3 gene.


IgA nephropathy, susceptibility to, 3

description: Any IgA glomerulonephritis in which the cause of the disease is a mutation in the SPRY2 gene.


Diamond-Blackfan anemia 1

description: Any Diamond-Blackfan anemia in which the cause of the disease is a mutation in the RPS19 gene.


description: BTDD is an autosomal dominant disorder characterized by brachycephaly, trichomegaly, and developmental delay. Although it is caused by dysfunction of the ribosome, patients do not have anemia (summary by {2:Paolini et al., 2017}).


Diamond-Blackfan anemia 5

description: Any Diamond-Blackfan anemia in which the cause of the disease is a mutation in the RPL35A gene.


Diamond-Blackfan anemia 9

description: Any Diamond-Blackfan anemia in which the cause of the disease is a mutation in the RPS10 gene.


name: 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome

description: Any 3-methylglutaconic aciduria in which the cause of the disease is a mutation in the SERAC1 gene.


van den Ende-Gupta syndrome

description: Van den Ende-Gupta syndrome is a very rare syndrome characterized by blepharophimosis, arachnodactyly, joint contractures, and characteristic dysmorphic features.


Diamond-Blackfan anemia 11

description: Any Diamond-Blackfan anemia in which the cause of the disease is a mutation in the RPL26 gene.


Floating-Harbor syndrome

description: Floating-Harbor syndrome is a genetic developmental disorder characterized by facial dysmorphism, short stature with delayed bone age, and expressive language delay.


autosomal dominant sensory ataxia 1

description: Any hereditary ataxia in which the cause of the disease is a mutation in the RNF170 gene.


name: inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3

description: Any inclusion body myopathy with Paget disease of bone and frontotemporal dementia in which the cause of the disease is a mutation in the HNRNPA1 gene.


amyotrophic lateral sclerosis type 20

description: Any amyotrophic lateral sclerosis in which the cause of the disease is a mutation in the HNRNPA1 gene.


acrofacial dysostosis Cincinnati type

description: Any acrofacial dysostosis in which the cause of the disease is a mutation in the POLR1A gene.


description: A syndrome is characterized by ataxia, delayed dentition, hypomyelination and cerebral atrophy. So far, eight cases have been described.


Leber congenital amaurosis 2

description: Any Leber congenital amaurosis in which the cause of the disease is a mutation in the RPE65 gene.


retinitis pigmentosa 20

description: Any retinitis pigmentosa in which the cause of the disease is a mutation in the RPE65 gene.


name: combined oxidative phosphorylation defect type 11

description: Any combined oxidative phosphorylation deficiency in which the cause of the disease is a mutation in the RMND1 gene.


occult macular dystrophy

description: Occult macular dystrophy is a rare, genetic retinal dystrophy disease characterized by bilateral progressive decline of visual acuity, due to retinal dysfunction confined only to the macula, associated with normal fundus and fluorescein angiograms and severely attenuated focal macular and multifocal electroretinograms.


name: hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism

description: Any leukodystrophy in which the cause of the disease is a mutation in the POLR3B gene.


Moyamoya disease 2

description: Any Moyamoya disease in which the cause of the disease is a mutation in the RNF213 gene.


name: SESSILE SERRATED POLYPOSIS CANCER SYNDROME


name: progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 2

description: Any progressive external ophthalmoplegia with mitochondrial DNA deletions in which the cause of the disease is a mutation in the RNASEH1 gene.


Aicardi-Goutieres syndrome 2

description: Any Aicardi-Goutieres syndrome in which the cause of the disease is a mutation in the RNASEH2B gene.


cerebellar ataxia-hypogonadism syndrome

description: Cerebellar ataxia-hypogonadism syndrome is a very rare autosomal recessive neurodegenerative disorder characterized by the combination of progressive cerebellar ataxia with onset from early childhood to the fourth decade, and hypogonadotropic hypogonadism (delayed puberty and lack of secondary sex characteristics). Cerebellar ataxia-hypogonadism syndrome belongs to a clinical continuum of neurodegenerative disorders along with clinically overlapping disorders such as ataxia-hypogonadism-choroidal dystrophy syndrome.


Aicardi-Goutieres syndrome 3

description: Any Aicardi-Goutieres syndrome in which the cause of the disease is a mutation in the RNASEH2C gene.


name: autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency

description: Any autosomal recessive mendelian susceptibility to mycobacterial diseases due to a complete deficiency in which the cause of the disease is a mutation in the RORC gene.


Bothnia retinal dystrophy

description: A rare form of retinal dystrophy, seen mostly in Northern Sweden, presenting in early childhood with night blindness and progressive maculopathy with a decrease in visual acuity, eventually leading to blindness by adulthood. Retinal degeneration, without obvious bone spicule formation, accompanied by affected visual fields and the typical presence of retinitis punctata albescens in the posterior pole are also noted.


Newfoundland cone-rod dystrophy

description: Any cone-rod dystrophy in which the cause of the disease is a mutation in the RLBP1 gene.


prostate cancer, hereditary, 1

description: Any familial prostate cancer in which the cause of the disease is a mutation in the RNASEL gene.


prostate cancer, hereditary, 2

description: Any familial prostate cancer in which the cause of the disease is a mutation in the ELAC2 gene.


name: combined oxidative phosphorylation defect type 17

description: Any combined oxidative phosphorylation deficiency in which the cause of the disease is a mutation in the ELAC2 gene.


name: gaze palsy, familial horizontal, with progressive scoliosis 1


intellectual disability, X-linked 61

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


Aicardi-Goutieres syndrome 4

description: Any Aicardi-Goutieres syndrome in which the cause of the disease is a mutation in the RNASEH2A gene.


name: NASOPHARYNGEAL CARCINOMA, SUSCEPTIBILITY TO, 3


brachydactyly type B1

description: Any brachydactyly type B in which the cause of the disease is a mutation in the ROR2 gene.


autosomal recessive Robinow syndrome

description: Autosomal recessive Robinow syndrome (RRS) is the less common type of Robinow syndrome (RS) characterized by short-limb dwarfism, costovertebral segmentation defects and abnormalities of the head, face and external genitalia.


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

description: Autosomal dominant Charcot-Marie-Tooth disease type 2N (CMT2N) is a mild form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy, characterized by distal legs sensory loss and weakness that can be asymmetric. Tendon reflexes are reduced in the knees and absent in ankles. Progression is slow.


name: developmental and epileptic encephalopathy, 29

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


primary ciliary dyskinesia 12

description: Any primary ciliary dyskinesia in which the cause of the disease is a mutation in the RSPH9 gene.


nonsyndromic congenital nail disorder 4

description: Any isolated congenital anonychia in which the cause of the disease is a mutation in the RSPO4 gene.


name: combined oxidative phosphorylation defect type 2

description: Combined oxidative phosphorylation defect type 2 is a rare mitochondrial disorder due to a defect in mitochondrial protein synthesis characterized by severe intrauterine growth retardation, neonatal limb edema and redundant skin on the neck (hydrops), developmental brain defects (corpus callosum agenesis, ventriculomegaly), brachydactyly, dysmorphic facial features with low set ears, severe intractable neonatal lactic acidosis with lethargy, hypotonia, absent spontaneous movements and fatal outcome. Markedly decreased activity of complex I, II + III and IV in muscle and liver have been determined.


Bartter disease type 1

description: An autosomal recessive subtype of Bartter syndrome caused by mutation(s) in the SLC12A1 gene, encoding solute carrier family 12 member 1.The onset occurs in the antenatal period, and may be characterized by polyhydramnios, premature birth, failure to thrive and mental retardation. Clinical variability in the severity of symptoms exists and an essential feature of antenatal forms of Bartter syndrome is marked hypercalciuria.


diastrophic dysplasia

description: Diastrophic dwarfism is a rare disorder marked by short stature with short extremities (final adult height is 120cm +/- 10cm), and joint malformations leading to multiple joint contractures (principally involving the shoulders, elbows, interphalangeal joints and hips).


achondrogenesis type IB

description: Achondrogenesis type 1B (ACG1B), a form of achondrogenesis, is a rare lethal skeletal dysplasia characterized by severe micromelia with very short fingers and toes, a flat face, a short neck, thickened soft tissue around the neck, hypoplasia of the thorax, protuberant abdomen, a hydropic fetal appearance and distinctive histological features of the cartilage.


atelosteogenesis type II

description: A lethal perinatal bone dysplasia characterized by limb shortening, normal sized skull with cleft palate, hitchhiker thumbs, distinctive facial dysmorphism and radiographic skeletal features, caused by mutations in the diastrophic dysplasia sulfate transporter gene.


multiple epiphyseal dysplasia type 4

description: Multiple epiphyseal dysplasia type 4 is a multiple epiphyseal dysplasia with a late-childhood onset, characterized by joint pain involving hips, knees, wrists, and fingers with occasional limitation of joint movements, deformity of hands, feet, and knees (club foot, clinodactyly, brachydactyly), scoliosis and slightly reduced adult height. Radiographs display flat epiphyses with early arthritis of the hip, and double-layered patella. Multiple epiphyseal dysplasia type 4 follows an autosomal recessive mode of transmission. The disease is allelic to diastrophic dwarfism, atelosteogenesis type 2 and achondrogenesis type 1B with whom it forms a clinical continuum.


primary ciliary dyskinesia 24

description: Any primary ciliary dyskinesia in which the cause of the disease is a mutation in the RSPH1 gene.


name: progressive spondyloepimetaphyseal dysplasia-short stature-short fourth metatarsals-intellectual disability syndrome


familial isolated congenital asplenia

description: Familial isolated congenital asplenia is a rare, non-syndromic, potentially life-threatening visceral malformation characterized by the absence of normal spleen function, resulting in a primary immunodeficiency. Typically, the condition manifests with severe, recurrent, overwhelming infections (especially pneumococcal sepsis) in otherwise apparently healthy infants. In adults with no history of severe sepsis in infancy, thrombocytosis may be the presenting sign. Howell-Jolly bodies on blood smears and an absent spleen on abdominal ultrasound examination are highly suggestive associated findings.


name: DYSKERATOSIS CONGENITA, AUTOSOMAL RECESSIVE 5

description: Dyskeratosis congenita caused by mutation(s) in the RTEL1 gene, encoding regulator of telomere elongation helicase 1.


name: PULMONARY FIBROSIS AND/OR BONE MARROW FAILURE SYNDROME, TELOMERE-RELATED, 3


name: developmental and epileptic encephalopathy, 25

description: Any early infantile epileptic encephalopathy in which the cause of the disease is a mutation in the SLC13A5 gene.


name: basal ganglia calcification, idiopathic, 1

description: An autosomal dominant condition caused by mutation(s) in the SLC20A2 gene, encoding sodium-dependent phosphate transporter 2. It is characterized by calcification of the basal ganglia.


primary ciliary dyskinesia 32

description: Any primary ciliary dyskinesia in which the cause of the disease is a mutation in the RSPH3 gene.


name: humerofemoral hypoplasia with radiotibial ray deficiency


name: Charcot-Marie-Tooth disease recessive intermediate B

description: Autosomal recessive intermediate Charcot-Marie-Tooth disease type B is an extremely rare subtype of autosomal recessive intermediate Charcot-Marie-Tooth (CMT) disease characterized by a CMT neuropathy associated with developmental delay, self-abusive behavior, dysmorphic features and vestibular Schwannoma. Motor nerve conduction velocities demonstrate features of both demyelinating and axonal pathology.


name: autosomal recessive nonsyndromic hearing loss 89

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


name: combined oxidative phosphorylation deficiency 34


name: hypotonia with lactic acidemia and hyperammonemia

description: This syndrome is characterized by severe hypotonia, lactic academia and congenital hyperammonaemia.


hereditary spastic paraplegia 12

description: Autosomal dominant spastic paraplegia type 12 is a pure form of hereditary spastic paraplegia characterized by a childhood- to adulthood-onset of slowly progressive lower limb spasticity and hyperreflexia of lower extremities, extensor plantar reflexes, distal sensory impairment, variable urinary dysfunction and pes cavus.


name: combined oxidative phosphorylation deficiency 36


name: optic atrophy 10 with or without ataxia, intellectual disability, and seizures


name: autosomal recessive spinocerebellar ataxia 15

description: Any autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome in which the cause of the disease is a mutation in the RUBCN gene.


vesicoureteral reflux 2

description: Any vesicoureteral reflux in which the cause of the disease is a mutation in the ROBO2 gene.


retinitis pigmentosa 1

description: Any retinitis pigmentosa in which the cause of the disease is a mutation in the RP1 gene.


name: inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2

description: Any inclusion body myopathy with Paget disease of bone and frontotemporal dementia in which the cause of the disease is a mutation in the HNRNPA2B1 gene.


primary hyperoxaluria type 1

description: A rare disorder of glyoxylate metabolism characterized by the accumulation of oxalate due to a deficiency of the peroxisomal hepatic enzyme L-alanine: glyoxylate aminotransferase (AGT). Clinical presentation is variable, ranging from occasional symptomatic nephrolithiasis to nephrocalcinosis and end-stage renal disease with systemic involvement.


name: cystic leukoencephalopathy without megalencephaly

description: Cystic leukoencephalopathy without megalencephaly is characterized by non-progressive leukoencephalopathy, bilateral cysts in the anterior part of the temporal lobe, cerebral white matter anomalies and severe psychomotor impairment. Less than 50 patients have been described in the literature so far. Inheritance is most likely autosomal recessive.


name: combined oxidative phosphorylation defect type 9

description: Combined oxidative phosphorylation defect type 9 is a rare mitochondrial disease due to a defect in mitochondrial protein synthesis characterized by initially normal growth and development followed by the infantile-onset of failure to thrive, psychomotor delay, poor feeding, dyspnea, severe hypertrophic cardiomyopathy and hepatomegaly. Laboratory studies report increased plasma lactate and alanine, abnormal liver enzymes and decreased activity of mitochondrial respiratory chain complexes I, III, IV, and V.


RIDDLE syndrome

description: An autosomal recessive disease characterized by increased radiosensitivity, immunodeficiency, mild motor control and learning difficulties, facial dysmorphism, and short stature that has material basis in homozygous or compound heterozygous mutation in the RNF168 gene on chromosome 3q29.


name: infantile hypertrophic cardiomyopathy due to MRPL44 deficiency

description: Infantile hypertrophic cardiomyopathy due to MRPL44 deficiency is a rare mitochondrial oxidative phosphorylation disorder with complex I and IV deficiency characterized by hypertrophic cardiomyopathy, hepatic steatosis with elevated liver transaminases, exercise intolerance and muscle weakness. Neuro-opthalmological features (hemiplegic migraine, Leigh-like lesions on brain MRI, pigmentary retinopathy) have been reported later in life.


ribose-5-P isomerase deficiency

description: Ribose-5-P isomerase deficiency is an extremely rare, hereditary, disorder of pentose phosphate metabolism characterized by progressive leukoencephalopathy and a highly increased ribitol and D-arabitol levels in the brain and body fluids. Clinical presentation includes psychomotor delay, epilepsy, and childhood-onset slow neurological regression with ataxia, spasticity, optic atrophy and sensorimotor neuropathy.


amelocerebrohypohidrotic syndrome

description: Kohlschütter-TC6nz syndrome (KTS) is a genetically heterogeneous autosomal recessive syndrome characterized by the triad of amelogenesis imperfect, infantile onset epilepsy, intellectual disability with or without regression and dementia.


name: intellectual developmental disorder with or without epilepsy or cerebellar ataxia


Cornelia de Lange syndrome 2

description: An X-linked inherited form of Cornelia De Lange syndrome caused by mutations in the SMC1A gene mapped to chromosome Xp11.22. Patients have a milder form of the syndrome compared to patients with the NIPBL gene mutation.


Treacher Collins syndrome 2

description: Any Treacher-Collins syndrome in which the cause of the disease is a mutation in the POLR1D gene.


retinitis pigmentosa 3

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


name: Retinitis Pigmentosa, X-Linked, And Sinorespiratory Infections, With Or Without Deafness


Treacher Collins syndrome 3

description: Any Treacher-Collins syndrome in which the cause of the disease is a mutation in the POLR1C gene.


hypomyelinating leukodystrophy 11

description: Any leukodystrophy in which the cause of the disease is a mutation in the POLR1C gene.


Legius syndrome

description: Legius syndrome, also known as NF1-like syndrome, is a rare, genetic skin pigmentation disorder characterized by multiple cafC)-au-lait macules with or without axillary or inguinal freckling.


name: intellectual disability, autosomal dominant 47


Bailey-Bloch congenital myopathy

description: Bailey-Bloch congenital myopathy is a neuromuscular disorder characterized by weakness, arthrogryposis, kyphoscoliosis, short stature, cleft palate, ptosis and susceptibility to malignant hyperthermia during anesthesia.


name: hyper-IgE recurrent infection syndrome 1, autosomal dominant

description: A condition of decreased or absent presence or activity of signal transducer and activator of transcription 3 protein. Deficiency of this protein is associated with hyper-IgE syndrome.


name: STAT3-related early-onset multisystem autoimmune disease

description: An autosomal dominant condition caused by mutation(s) in the STAT3 gene, encoding signal transducer and activator of transcription 3. It is characterized by variable features along a spectrum of autoimmune disorders affecting multiple organs. Common manifestations may include insulin-dependent diabetes mellitus and autoimmune enteropathy, or celiac disease, and autoimmune hematologic disorders. Other features include short stature and nonspecific dermatitis.


description: STING-associated vasculopathy with onset in infancy (SAVI) is a rare, genetic autoinflammatory disorder, type I interferonopathy due to constitutive STING (STimulator of INterferon Genes) activation, characterized by neonatal or infantile onset systemic inflammation and small vessel vasculopathy resulting in severe skin, pulmonary and joint lesions. Patients present with intermittent low-grade fever, recurrent cough and failure to thrive, in association with progressive interstitial lung disease, polyarthritis and violaceous scaling lesions on fingers, toes, nose, cheeks, and ears (which are exacerbated by cold exposure) that often progress to chronic acral ulceration, necrosis and autoamputation.


premature ovarian failure 7

description: Any primary ovarian failure in which the cause of the disease is a mutation in the NR5A1 gene.


spermatogenic failure 8

description: Any azoospermia in which the cause of the disease is a mutation in the NR5A1 gene.


name: STT3A-congenital disorder of glycosylation

description: STT3A-CDG is a form of congenital disorders of N-linked glycosylation characterized by developmental delay, intellectual disability, failure to thrive, hypotonia and seizures. STT3A-CDG is caused by mutations in the gene STT3A (11q23.3).


name: STT3B-congenital disorder of glycosylation

description: STT3B-CDG is a form of congenital disorders of N-linked glycosylation characterized by intrauterine growth retardation, microcephaly, failure to thrive, developmental delay, intellectual disability, hypotonia, seizures, optic nerve atrophy and respiratory difficulties. Genital abnormalities (micropenis, hypoplastic scrotum, undescended testes) have also been reported. STT3B-CDG is caused by mutations in the gene STT3B (3p24.1).


name: developmental and epileptic encephalopathy, 4

description: Early infantile epileptic encephalopathy 4 (EIEE4) is a form of early infantile epileptic encephalopathy, which refers to a group of neurological conditions characterized by severe seizures beginning in infancy. EIEE4, specifically, is often associated with partial complex or tonic-clonic seizures, although other seizure types have been reported. Other signs and symptoms mayinclude intellectual disability, reduced muscle tone (hypotonia), hypsarrhythmia (an irregular pattern seen on EEG), dyskinesia (involuntary movement of the body), and spastic di- or quadriplegia. EIEE4 is caused by changes (mutations) in the STXBP1 gene and is inherited in an autosomal dominant manner. Treatment is based on the signs and symptoms present in each person. For example, certain medications are often prescribed to help control seizures, although they are not always effective in all people with the condition.


Adams-Oliver syndrome 3

description: Any Adams-Oliver syndrome in which the cause of the disease is a mutation in the RBPJ gene.


name: syndromic X-linked intellectual disability Snyder type

description: Snyder-Robinson syndrome (SRS) is an X-linked intellectual disability syndrome, including also hypotonia, an unsteady gait, osteoporosis, kyphoscoliosis and facial asymmetry. Severe generalized psychomotor evolving to moderate to profound global intellectual disability is also observed.


name: developmental and epileptic encephalopathy, 5

description: Any early infantile epileptic encephalopathy in which the cause of the disease is a mutation in the SPTAN1 gene.


spinocerebellar ataxia type 5

description: Spinocerebellar ataxia type 5 (SCA5) is a rare subtype of autosomal dominant cerebellar ataxia type III (ADCA type III) characterized by the early-onset of cerebellar signs with eye movement abnormalities and a very slow disease progression.


name: autosomal recessive spinocerebellar ataxia 14

description: Spectrin-associated autosomal recessive cerebellar ataxia is a rare, genetic neurological disease, due to SPTBN2 mutations, characterized by global development delay in infancy, followed by childhood-onset gait ataxia with limb dysmetria and dysdiadochokinesia, mild to severe intellectual disability, development of cerebellar atrophy, and abnormal eye movements (including a convergent squint, hypometric saccades, jerky pursuit movements and incomplete range of movement).


name: succinic semialdehyde dehydrogenase deficiency

description: Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare neurometabolic disorder of gamma-aminobutyric acid (GABA) metabolism with a nonspecific clinical presentation (ranging from mild to severe) with the most frequent symptoms being cognitive impairment with prominent deficit in expressive language, hypotonia, ataxia, epilepsy, and behavioral dysregulation.


premature ovarian failure 8

description: Any primary ovarian failure in which the cause of the disease is a mutation in the STAG3 gene.


name: Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency

description: A genetic variant of Mendelian susceptibility to mycobacterial diseases characterized by a partial defect in the interferon (IFN)-gamma pathway, leading to mild mycobacterial infections.


name: autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome

description: Autoimmune enteropathy and endocrinopathy-susceptibility to chronic infections syndrome is an extremely rare, autosomal dominant immunological disorder characterized by variable enteropathy, endocrine disorders (e.g. type 1 diabetes mellitus, hypothyroidism), immune dysregulation with pulmonary and blood-borne bacterial infections, and fungal infections (chronic mucocutaneous candidiasis) developing in infancy. Other manifestations include short stature, eczema, hepatosplenomegaly, delayed puberty, and osteoporosis/osteopenia.


name: primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection

description: Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection is a rare primary immunodeficiency due to a defect in innate immunity disorder characterized by selective susceptibility to viral infections, particularly after systemic challenge with live viral vaccines, such as the measles, mumps and rubella (MMR) vaccine. Patients present severe, potentially fatal, manifestations to viral illness, including encephalitis, hepatitis and pneumonitis.


atransferrinemia

description: Congenital atransferrinemia is a very rare hematologic disease caused by a transferrin (TF) deficiency and characterized by microcytic, hypochromic anemia (manifesting with pallor, fatigue and growth retardation) and iron overload, and that can be fatal if left untreated.


name: autosomal recessive nonsyndromic hearing loss 16

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


mulibrey nanism

description: A prenatal onset growth disorder with multiorgan manifestations.


mucosulfatidosis

description: Multiple sulfatase deficiency (MSD) is a very rare and fatal lysosomal storage disease characterized by a clinical phenotype that combines the features of different sulfatase deficiencies (whether lysosomal or not) that can have neonatal (most severe), infantile (most common) and juvenile (rare) presentations with manifestations including hypotonia, coarse facial features, mild deafness, skeletal anomalies, ichthyosis, hepatomegaly, developmental delay, progressive neurologic deterioration and hydrocephalus.


name: congenital stationary night blindness 1C

description: Any congenital stationary night blindness in which the cause of the disease is a mutation in the TRPM1 gene.


name: progressive familial heart block type IB

description: Any progressive familial heart block in which the cause of the disease is a mutation in the TRPM4 gene.


intestinal hypomagnesemia 1

description: Primary hypomagnesemia with secondary hypocalcemia (PHSH) is a form of familial primary hypomagnesemia (FPH), characterized by severe hypomagnesemia and secondary hypocalcemia associated with neurological symptoms, including generalized seizures, tetany and muscle spasms. PHSH may be fatal or may result in chronic irreversible neurological complications.


name: amyotrophic lateral sclerosis-parkinsonism-dementia complex


hereditary spherocytosis type 2

description: Any hereditary spherocytosis in which the cause of the disease is a mutation in the SPTB gene.


name: neuropathy, hereditary sensory and autonomic, type 1C

description: A hereditary sensory and autonomic neuropathy type 1 that has material basis in heterozygous mutation in the SPTLC2 gene on chromosome 14q24.


46,XY sex reversal 1

description: Sex reversal in an individual with 46,XY karyotype caused by point mutations or deletions in the SRY gene, encoding sex-determining region Y protein.


46,XX sex reversal 1

description: Presence of testes in an individual with a 46,XX karyotype associated with translocation of the SRY gene, encoding the transcription factor sex-determining region Y protein (SRY-positive).


name: autosomal recessive nonsyndromic hearing loss 79

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


MHC class I deficiency

description: Immunodeficiency by defective expression of HLA class 1 is a very rare, primary, genetic, immunodeficiency disorder characterized by partial or complete absence of human leukocyte antigen class I expression resulting in a non-specific clinical picture of impaired immune response and susceptibility to infections.


name: SSR4-congenital disorder of glycosylation

description: A form of congenital disorders of N-linked glycosylation characterized by neurologic abnormalities (global developmental delay in language, social skills and fine and gross motor development, intellectual disability, hypotonia, microcephaly, seizures/epilepsy), facial dysmorphism (deep set eyes, large ears, hypoplastic vermillion of upper lip, large mouth with widely spaced teeth), feeding problems often due to chewing difficulties and aversion to food with certain textures, failure to thrive, gastrointestinal abnormalities (reflux or vomiting) and strabismus. The disease is caused by mutations in the gene SSR4(Xq28).


name: autosomal recessive congenital ichthyosis 11


name: ichthyosis, congenital, autosomal recessive 14


name: growth hormone insensitivity with immune dysregulation 1, autosomal recessive


description: An autosomal recessive condition caused by mutation(s) in the STAMBP gene, encoding STAM-binding protein. It is characterized by severe microcephaly, diffuse cutaneous capillary malformations, refractory epilepsy, and developmental delay.


name: congenital lipoid adrenal hyperplasia due to STAR deficency

description: Congenital lipoid adrenal hyperplasia (CLAH) is one of the most severe forms of congenital adrenal hyperplasia (CAH) characterized by severe adrenal insufficiency and sex reversal in males.


name: microcephaly 7, primary, autosomal recessive

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


name: combined immunodeficiency due to STIM1 deficiency

description: Aform of combined immunodeficiency due to Calcium release activated Ca2+(CRAC) channel dysfunction characterized by recurrent infections, autoimmunity, congenital myopathy and ectodermal dysplasia.


Stormorken syndrome

description: Stormorken-Sjaastad-Langslet syndrome is characterized by thrombocytopathy, asplenia, miosis, muscle fatigue, migraine, dyslexia, and ichthyosis. It has been described in six members of one family. It is transmitted as an autosomal dominant trait.


Sturge-Weber syndrome

description: Sturge-Weber syndrome (SWS) is a rare congenital neurocutaneous disorder characterized by facial capillary malformations and/or cerebral and ocular ipsilateral vascular malformations that result in variable degrees of ocular and neurological anomalies.


uncombable hair syndrome 3

description: Any uncombable hair syndrome in which the cause of the disease is a mutation in the TCHH gene.


name: dopa-responsive dystonia due to sepiapterin reductase deficiency

description: Dopa responsive dystonia (DRD) due to sepiapterin reductase deficiency (SRD) is a very rare neurometabolic disorder characterized by dystonia with diurnal fluctuations, axial hypotonia, oculogyric crises, and delays in motor and cognitive development.


immunoglobulin A deficiency 2

description: Any selective IgA deficiency disease in which the cause of the disease is a mutation in the TNFRSF13B gene.


name: herpes simplex encephalitis, susceptibility to, 3

description: A Mendelian susceptibility or predisposition to herpes simplex infection induced encephalitis in which the cause of the diseas is a mutation in the TRAF3 gene.


Seckel syndrome 9

description: Any Seckel syndrome in which the cause of the disease is a mutation in the TRAIP gene.


name: catecholaminergic polymorphic ventricular tachycardia 5

description: Any catecholaminergic polymorphic ventricular tachycardia in which the cause of the disease is a mutation in the TRDN gene.


name: diarrhea-vomiting due to trehalase deficiency

description: This syndrome is characterized by diarrhea and vomiting after ingestion of trehalose, a disaccharide found mainly in mushrooms.


name: autosomal recessive nonsyndromic hearing loss 91

description: Any autosomal recessive nonsyndromic deafness in which the cause of the disease is a mutation in the SERPINB6 gene.


name: early-onset generalized limb-onset dystonia

description: A rare movement disorder characterized by involuntary, repetitive, sustained muscle contractions or postures involving one or more sites of the body.


osteogenesis imperfecta type 17

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


name: combined oxidative phosphorylation defect type 26

description: Any combined oxidative phosphorylation deficiency in which the cause of the disease is a mutation in the TRMT5 gene.


type 1 diabetes mellitus 5

description: An inherited susceptibility or predisposition to developing type 1 diabetes mellitus in which the cause of the disease is a mutation in the SUMO4 gene.


name: arthrogryposis, renal dysfunction, and cholestasis 2

description: Any arthrogryposis-renal dysfunction-cholestasis syndrome in which the cause of the disease is a mutation in the VIPAS39 gene.


elliptocytosis 2

description: Any hereditary elliptocytosis in which the cause of the disease is a mutation in the SPTA1 gene.


pyropoikilocytosis, hereditary

description: An autosomal recessive inherited severe hemolytic anemia. It is a subtype of hereditary elliptocytosis and is characterized by partial spectrin deficiency.


hereditary spherocytosis type 3

description: Any hereditary spherocytosis in which the cause of the disease is a mutation in the SPTA1 gene.


name: neuropathy, hereditary sensory and autonomic, type 1A

description: An axonal form of hereditary motor and sensory neuropathy distinguished by prominent early sensory loss and later positive sensory phenomena, caused by mutations in SPTLC1.


name: polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1


name: systemic lupus erythematosus, susceptibility to, 11

description: Any systemic lupus erythematosus in which the cause of the disease is a mutation in the STAT4 gene.


name: combined immunodeficiency due to STK4 deficiency

description: A rare, genetic combined T and B cell immunodeficiency characterized by T- and B-cell lymphopenia, hypergammaglobulinemia and intermittent neutropenia. It presents with recurrent opportunistic viral, bacterial and fungal infections involving skin (cutaneous papillomatosis, molluscum contagiosum, skin abscesses, mucocutaneous candidiasis), upper and lower respiratory tract or septicemia. Other clinical features include autoimmune manifestations (autoimmune hemolytic anemia) and congenital heart defects (atrial septal defects, patent foramen ovale, mitral, triscupid and pulmonary valve insufficiency).


Charcot-Marie-Tooth disease type 4K

description: SURF1-related Charcot-Marie-Tooth disease type 4 (CMT4K) is a subtype of Charcot-Marie-Tooth disease type 4 characterized by childhood onset of severe, progressive, demyelinating sensorimotor neuropathy manifesting with distal muscle weakness and atrophy of hands and feet, distal sensory impairment (vibration and pinprick) of lower limbs, lactic acidosis, areflexia and severely reduced motor nerve conduction velocities (25 m/s or less). Patients may also present kyphoscoliosis, nystagmus, hearing loss, cerebellar ataxia and/or brain MRI abnormalities (putaminal and periaqueductal lesions).


name: hypomyelination with brain stem and spinal cord involvement and leg spasticity


name: autosomal dominant nonsyndromic hearing loss 36

description: Any autosomal dominant nonsyndromic deafness in which the cause of the disease is a mutation in the TMC1 gene.


name: autosomal recessive nonsyndromic hearing loss 7

description: Any autosomal recessive nonsyndromic deafness in which the cause of the disease is a mutation in the TMC1 gene.


dentin dysplasia type I

description: Dentin dysplasia type I (DD-I) is a rare form of dentin dysplasia (DD) characterized by sharp conical short roots or rootless teeth.


name: psychomotor retardation, epilepsy, and craniofacial dysmorphism


description: A non-severe combined immunodeficiency disorder manifesting with recurrent respiratory infections, candidiasis, diarrhea, and failure to thrive. Patients show a clear predisposition to herpes viral infections, and features of immune dysregulation, including hypereosinophilia, vitiligo, and alopecia areata. Other features include lymphadenopathy and hepatosplenomegaly. CD3+ T-cells express TCR- gamma|delta, but little or no TCR-alpha|beta.


name: atypical hemolytic-uremic syndrome with thrombomodulin anomaly


spermatogenic failure 4

description: Any azoospermia in which the cause of the disease is a mutation in the SYCP3 gene.


name: autosomal recessive nonsyndromic hearing loss 76

description: Any autosomal recessive nonsyndromic deafness in which the cause of the disease is a mutation in the SYNE4 gene.


early-onset Parkinson disease 20

description: Any Parkinson disease in which the cause of the disease is a mutation in the SYNJ1 gene.


name: developmental and epileptic encephalopathy, 53


intellectual disability, X-linked 105

description: Any non-syndromic X-linked intellectual disability in which the cause of the disease is a mutation in the USP27X gene.


name: Cushing disease due to pituitary adenoma

description: Cushing's syndrome due to abnormally high secretion of adrenocorticotropic hormone (ACTH) from the pituitary gland.


name: leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome

description: This disease is characterized by progressive cerebellar ataxia with pyramidal and spinal cord dysfunction, associated with distinctive MRI anomalies and increased lactate in the abnormal white matter.


Usher syndrome type 3B

description: Any Usher syndrome in which the cause of the disease is a mutation in the HARS gene.


name: autosomal dominant Charcot-Marie-Tooth disease type 2W

description: Any Charcot-Marie-Tooth disease type 2 in which the cause of the disease is a mutation in the HARS gene.


name: cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome


name: combined oxidative phosphorylation defect type 14

description: Any combined oxidative phosphorylation deficiency in which the cause of the disease is a mutation in the FARS2 gene.


hereditary spastic paraplegia 77

description: Autosomal recessive spastic paraplegia type 77 is a rare, pure or complex hereditary spastic paraplegia characterized by an infancy to childhood onset of slowly progressive lower limb spasticity, delayed motor milestones, gait disturbances, hyperreflexia and various muscle abnormalities, including weakness, hypotonia, intention tremor and amyotrophy. Ocular abnormalities (e.g. strabismus, ptosis) and other neurological abnormalities, such as dysarthria, seizures and extensor plantar responses, may also be associated.


Perrault syndrome 4

description: Any Perrault syndrome in which the cause of the disease is a mutation in the LARS2 gene.


name: hydrops-lactic acidosis-sideroblastic anemia-multisystemic failure syndrome


name: severe early-onset pulmonary alveolar proteinosis due to MARS deficiency


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

description: Autosomal dominant Charcot-Marie-Tooth disease type 2U (CMT2U) is a subtype of autosonal dominant Charcot-Marie-Tooth disease type 2 characterized by late adult-onset (50-60 years of age) of slowly progressive, axonal, peripheral sensorimotor neuropathy resulting in distal upper limb and proximal and distal lower limb muscle weakness and atrophy, in conjunction with distal, panmodal sensory impairment in upper and lower limbs. Tendon reflexes are reduced and nerve conduction velocities range from reduced to absent. Neuropathic pain has also been associated.


name: combined oxidative phosphorylation defect type 24

description: Any combined oxidative phosphorylation deficiency in which the cause of the disease is a mutation in the NARS2 gene.


amyotrophic lateral sclerosis type 15

description: Any amyotrophic lateral sclerosis in which the cause of the disease is a mutation in the UBQLN2 gene.


name: choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome

description: Choanal atresia - deafness - cardiac defects - dysmorphism syndrome, also known as Burn-McKeown syndrome, is an extremely rare multiple congenital anomaly syndrome characterized by bilateral choanal atresia associated with a characteristic cranio-facial dysmorphism (hypertelorism with narrow palpebral fissures, coloboma of inferior eyelid with presence of eyelashes medial to the defect, prominent nasal bridge, thin lips, prominent ears), that can be accompanied by hearing loss, unilateral cleft lip, preauricular tags, cardiac septal defects and anomalies of the kidneys. The features of this syndrome overlaps considerably with those of the CHARGE syndrome.


name: oculocerebrofacial syndrome, Kaufman type


Schnyder corneal dystrophy

description: Schnyder corneal dystrophy (SCD) is a rare form of stromal corneal dystrophy characterized by corneal clouding or crystals within the corneal stroma, and a progressive decrease in visual acuity.


vitamin D-dependent rickets, type 2A

description: Rickets caused by a defect in the VDR gene, encoding the vitamin D receptor. This form of rickets is characterized by hypocalcemia, elevated 1,25-dihydroxyvitamin D (calcitriol) concentrations and may also manifest with alopecia.


UV-sensitive syndrome 3

description: Any UV-sensitive syndrome in which the cause of the disease is a mutation in the UVSSA gene.


spastic ataxia 1

description: Any autosomal dominant spastic ataxia in which the cause of the disease is a mutation in the VAMP1 gene.


familial caudal dysgenesis

description: Familial caudal dysgenesis is a rare, genetic, developmental defect during embryogenesis disorder characterized by varying degrees of caudal dysgenesis, ranging from a single umbilical artery or imperforate anus to full sirenomelia, in several members of the same family. Phenotype includes lumbosacral agenesis, anal atresia or ectopia, genitourinary abnormalities, components of VATER or VACTERL association, and facial dysmorphism (flat facies, abnormal ears, bilateral epicanthic folds, depressed nasal bridge, micrognathia). Additional features reported include cardiovascular (e.g. endocardial cushion defect, hypoplasia of pulmonary artery) and skeletal (kyphosis, hemipelvis) anomalies.


immunodeficiency 47

description: Any primary immunodeficiency disease in which the cause of the disease is a mutation in the ATP6AP1 gene.


autosomal recessive cutis laxa type 2D

description: An autosomal recessive cutis laxa type II classic type characterized by cardiovascular and neurologic involvement and that has material basis in homozygous mutation in the ATP6V1A gene on chromosome 3q13.


name: epileptic encephalopathy, infantile or early childhood, 3


name: renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss


Zimmermann-Laband syndrome 2

description: Any Zimmermann-Laband syndrome in which the cause of the disease is a mutation in the ATP6V1B2 gene.


name: autosomal dominant deafness - onychodystrophy syndrome

description: Dominant deafness-onychodystrophy (DDOD) syndrome is a multiple congenital anomalies syndrome characterized by congenital hearing impairment, small or absent nails on the hands and feet, and small terminal phalanges.