3811
(6.1%)

Paroxysmal non-kinesigenic dyskinesia

Trismus

Autosomal dominant inheritance

Paroxysmal non-kinesigenic dyskinesia (PNKD) is a form of paroxysmal dyskinesia (see this term), characterized by attacks of dystonic or choreathetotic movements precipitated by stress, fatigue, coffee or alcohol intake or menstruation.

3811
(6.1%)

Juvenile amyotrophic lateral sclerosis

Abnormality of the bladder

Juvenile amyotrophic lateral sclerosis (JALS) is a very rare severe motor neuron disease characterized by progressive upper and lower motor neuron degeneration causing facial spasticity, dysarthria, and gait disorders with onset before 25 years of age.

3811
(6.1%)

X-linked Charcot-Marie-Tooth disease type 4

Hearing impairment

X-linked recessive inheritance

X-linked Charcot-Marie-Tooth disease type 4 is a rare, genetic, axonal, peripheral sensorimotor neuropathy characterized by an X-linked recessive inheritance pattern and the neonatal- to early childhood-onset of severe, slowly progressive, distal muscle weakness and atrophy (in particular of the peroneal group), as well as sensory impairment (with the lower extremities being more affected than the upper extremities), pes cavus, areflexia and hammertoes. Sensorineural hearing loss and cognitive impairment may also be associated. Females are asymptomatic and do not display the phenotype.

3811
(6.1%)

Huntington disease-like 2

Behavioral abnormality

Autosomal dominant inheritance

Huntington disease-like 2 (HDL2) is a severe neurodegenerative disorder considered part of the neuroacanthocytosis syndromes (see this term) characterized by a triad of movement, psychiatric, and cognitive abnormalities.

3811
(6.1%)

Microcephaly-brachydactyly-kyphoscoliosis syndrome

Microcephaly

Microcephaly-brachydactyly-kyphoscoliosis syndrome is characterized by profound intellectual deficit in association with microcephaly, short stature, brachydactyly type D, a flattened occiput, downslanting palpebral fissures, low-set large ears, a broad prominent nose and kyphoscoliosis. It has been described in three sisters. The disorder is likely to be transmitted as an autosomal recessive trait.

3811
(6.1%)

Acromesomelic dysplasia, Grebe type

Brachydactyly

Autosomal recessive inheritance

A rare autosomal recessive acromesomelic dysplasia characterized by severe dwarfism at birth, abnormalities confined to limbs, severe shortening and deformity of long bones, fusion or absence of carpal and tarsal bones, ball shaped fingers and, occasionally, polydactyly and absent joints. As seen in acromesomelic dysplasia, Hunter-Thomson type and acromesomelic dysplasia, Maroteaux Type, facial features and intelligence are normal.

3811
(6.1%)

Fryns-Smeets-Thiry syndrome

Wide mouth

3811
(6.1%)

Ophthalmomandibulomelic dysplasia

Megalocornea

Autosomal dominant inheritance

Ophthalmomandibulomelic dysplasia is characterized by complete blindness due to corneal opacities, difficult mastication due to temporomandibular fusion and anomalies of the arms.

3811
(6.1%)

Autosomal dominant spastic paraplegia type 73

Urinary urgency

Autosomal dominant inheritance

A pure form of hereditary spastic paraplegia characterized by adult onset of crural spastic paraparesis, hyperreflexia, extensor plantar responses, proximal muscle weakness, mild muscle atrophy, decreased vibration sensation at ankles, and mild urinary dysfunction. Foot deformities have been reported to eventually occur in some patients. No abnormalities are noted on brain magnetic resonance imaging and peripheral nerve conduction velocity studies.

3811
(6.1%)

Autosomal dominant myopia-midfacial retrusion-sensorineural hearing loss-rhizomelic dysplasia syndrome

Glossoptosis

3811
(6.1%)

Familial infantile myoclonic epilepsy

Aggressive behavior

Autosomal recessive inheritance

A rare, genetic, infantile epilepsy syndrome disease characterized by neonatal- to infancy-onset myoclonic focal seizures occurring in various members of a family, associated in some with mild dysarthria, ataxia and borderline-to-moderate intellectual disability.

3811
(6.1%)

Autosomal dominant spastic paraplegia type 4

Urinary urgency

Autosomal dominant inheritance Genetic anticipation

A rare form of hereditary spastic paraplegia with high intrafamilial clinical variability, characterized in most cases as a pure phenotype with an adult onset (mainly the 3rd to 5th decade of life, but that can present at any age) of progressive gait impairment due to bilateral lower-limb spasticity and weakness as well as very mild proximal weakness and urinary urgency. In some cases, a complex phenotype is also reported with additional manifestations including cognitive impairment, cerebellar ataxia, epilepsy and neuropathy. A faster disease progression is noted in patients with a later age of onset.

3811
(6.1%)

Spinocerebellar ataxia type 20

Gaze-evoked nystagmus

Autosomal dominant inheritance

Spinocerebellar ataxia type 20 (SCA20) is a very rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by cerebellar dysarthria as the initial typical manifestation.

3811
(6.1%)

15q11q13 microduplication syndrome

Macrocephaly

Autosomal dominant inheritance Heterogeneous Multifactorial inheritance Sporadic

The 15q11-q13 microduplication (dup15q11-q13) syndrome is characterized by neurobehavioral disorders, hypotonia, cognitive deficit, language delay and seizures. Prevalence is unknown.

3811
(6.1%)

Craniodiaphyseal dysplasia

Hydrocephalus

Autosomal dominant inheritance Autosomal recessive inheritance

Craniodiaphyseal dysplasia is a rare sclerotic bone disorder with a variable phenotypic expression with massive generalized hyperostosis and sclerosis, particularly of the skull and facial bones, that may lead to severe deformity.

3811
(6.1%)

20q11.2 microdeletion syndrome

Hypertelorism

A rare, genetic, syndromic intellectual disability characterized by psychomotor delay, hypotonia, feeding difficulties, failure to thrive, anomalies of the hands and feet (clinodactyly, camptodactyly, brachydactyly, feet malposition), and craniofacial dysmorphism. Associated prenatal growth retardation, and gastrointestinal, heart and eye anomalies have been reported.

3811
(6.1%)

Lethal congenital contracture syndrome type 1

Hypertelorism

Autosomal recessive inheritance

Lethal congenital contracture syndrome type 1 is a rare, genetic arthrogryposis syndrome characterized by total fetal akinesia (detectable since the 13th week of gestation) accompanied by hydrops, micrognathia, pulmonary hypoplasia, pterygia and multiple joint contractures (usually flexion contractures in the elbows and extension in the knees), leading invariably to death before the 32nd week of gestation. Lack of anterior horn motoneurons, severe atrophy of the ventral spinal cord and severe skeletal muscle hypoplasia are characteristic neuropathological findings, with no evidence of other organ structural anomalies.

3811
(6.1%)

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

Cryptorchidism

Autosomal recessive inheritance

46, XY disorder of sex development (DSD; see this term) due to 5-alpha-reductase 2 (SRD5A2) deficiency is a disorder of sex development due to a defect in testosterone (T) metabolism resulting in incomplete intrauterine masculinization. Patients present an ambiguous external genitalia which varies from a female with a blind vaginal pouch to a fully male phenotype with pseudovaginal posterior hypospadias (see this term) or only micropenis.

3811
(6.1%)

Testicular regression syndrome

Abnormal morphology of female internal genitalia

Testicular regression syndrome (TRS) is a developmental anomaly characterized by the absence of one or both testicles with partial or complete absence of testicular tissue. TRS may vary from normal male with unilateral no-palpable testis through phenotypic male with micropenis, to phenotypic female. The phenotype depends on the extent and timing of the intrauterine accident in relation to sexual development.

3811
(6.1%)

Psychogenic movement disorders

Blepharospasm

Psychogenic movement disorders (PMD) are movement disorders that cannot be attributed to any known structural or neurochemical diseases, but represent the manifestation of an underlying psychiatric illness or malingering. Most cases of PMD fall in the psychiatric diagnostic category of conversion disorders of the motor subtype.

3811
(6.1%)

Autosomal dominant Charcot-Marie-Tooth disease type 2W

Gait disturbance

Autosomal dominant inheritance

3811
(6.1%)

Acrofacial dysostosis, Rodríguez type

Abnormality of the uterus

Autosomal recessive inheritance

A rare multiple malformative syndrome in which mandibulofacial dysostosis and severe limb reduction defects are associated with complex malformations of different organs and systems especially the CNS, urogenital tract, heart, and lungs. The mandibulofacial defect, characterized by extremely severe microretrognathism and cleft palate, causes death by respiratory distress. Limb reduction is severe and includes shoulder and pelvis hypoplasia, phocomelia with humerus hypoplasia, absent radius and ulna, complete absence of long bones of the legs, and various hand anomalies, predominantly preaxial reduction (absent thumbs). Other features include CNS malformations (agenesis of corpus callosum and acqueductal stenosis), lung anomalies (absent lung lobulation), complex cardiac malformations, and unicornis uterus. These infants also show facial dysmorphism and ear anomalies. The condition is a rare with an autosomal recessive mode of inheritance. The prognosis is poor and this condition leads to death in utero or shortly after birth.

3811
(6.1%)

Autosomal dominant spastic paraplegia type 36

Urinary urgency

Autosomal dominant inheritance

A complex form of hereditary spastic paraplegia, characterized by an onset in childhood or adulthood of progressive spastic paraplegia (with spastic gait, spasticity, lower limb weakness, pes cavus and urinary urgency) associated with the additional manifestation of peripheral sensorimotor neuropathy.

3811
(6.1%)

Acromesomelic dysplasia, Maroteaux type

Dolichocephaly

Autosomal recessive inheritance

A rare autosomal recessive acromesomelic dysplasia characterized by severe dwarfism (adult height >120 cm), both axial and appendicular involvement (shortening of the middle and distal segments of limbs and vertebral shortening), and with normal facial appearance and intelligence. It is a less severe form than acromesomelic dysplasia, Grebe type and acromesomelic dysplasia, Hunter-Thomson type .

3811
(6.1%)

Summitt syndrome

Tall stature

Autosomal recessive inheritance

Summitt syndrome is an extremely rare disorder originally described in two brothers and characterized by mild to severe craniosynostosis and syndactyly, obesity, and normal intelligence. Acrocephaly, brachydactyly, clinodactyly, mild syndactyly of the hands and feet, genu valgum and marked obesity were later described in another patient. There have been no further descriptions in the literature since 1979. Summitt syndrome could be a variant of Carpenter syndrome.

3811
(6.1%)

Autosomal dominant spastic paraplegia type 37

Urinary urgency

Autosomal dominant inheritance

A pure form of hereditary spastic paraplegia characterized by a childhood- to adulthood-onset of slowly progressive spastic gait, extensor plantar responses, brisk tendon reflexes in arms and legs, decreased vibration sense at ankles and urinary dysfunction. Ankle clonus is also reported in some patients.

3811
(6.1%)

Spinocerebellar ataxia type 29

Abnormal saccadic eye movements

Autosomal dominant inheritance

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

3811
(6.1%)

Autosomal dominant spastic paraplegia type 3

Urinary urgency

Autosomal dominant inheritance Heterogeneous

A rare, pure or complex subtype of hereditary spastic paraplegia, with highly variable phenotype, typically characterized by childhood-onset of minimally progressive, bilateral, mainly symmetric lower limb spasticity and weakness, associated with pes cavus, diminished vibration sense, sphincter disturbances and/or urinary bladder hyperactivity. Additional associated manifestations may include scoliosis, mild intellectual disability, optic atrophy, axonal motor neuropathy and/or distal amyotrophy.

3811
(6.1%)

Hypogonadotropic hypogonadism-retinitis pigmentosa syndrome

Hypogonadotropic hypogonadism

This syndrome is characterized by the association of hypogonadotropic hypogonadism (with primary amenorrhea and lack of secondary sexual development) and retinitis pigmentosa (see this term). It has been described in two sisters born to nonconsanguineous parents.

3811
(6.1%)

Macular corneal dystrophy

Hyperopic astigmatism

Autosomal recessive inheritance

Macular corneal dystrophy (MCD) is a rare, severe form of stromal corneal dystrophy (see this term) characterized by bilateral ill-defined cloudy regions within a hazy stroma, and eventually severe visual impairment.

3811
(6.1%)

Adenylosuccinate lyase deficiency

Thin upper lip vermilion

Autosomal recessive inheritance

A disorder of purine metabolism characterized by intellectual disability, psychomotor delay and/or regression, seizures, and autistic features.

3811
(6.1%)

Spectrin-associated autosomal recessive cerebellar ataxia

Strabismus

Autosomal recessive inheritance

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).

3811
(6.1%)

Autosomal recessive cerebellar ataxia-saccadic intrusion syndrome

Abnormality of eye movement

Autosomal recessive inheritance

A rare hereditary ataxia characterized by a progressive cerebellar ataxia associated with disruption of visual fixation by saccadic intrusions (overshooting horizontal saccades with macrosaccadic oscillations and increased velocity of larger saccades). It presents with progressive gait, trunk and limb ataxia with pyramidal tract signs (increased tendon reflexes and Babinski sign), myoclonic jerks, fasciculations, cerebellar dysarthria, sensorimotor axonal neuropathy with impaired joint position, vibration, temperature, pain sensations, pes cavus, and saccadic intrusions with characteristic overshooting horizontal saccades, macrosaccadic oscillations, and increased velocity of larger saccades, without other eye movement disturbances.

3811
(6.1%)

Spinocerebellar ataxia type 18

Hearing impairment

Autosomal dominant inheritance

Spinocerebellar ataxia type 18 (SCA18) is a very rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by sensory neuropathy and cerebellar ataxia.

3811
(6.1%)

Spinocerebellar ataxia type 17

Torticollis

Autosomal dominant inheritance

Spinocerebellar ataxia type 17 (SCA17) is a rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by a variable clinical picture which can include dementia, psychiatric disorders, parkinsonism, dystonia, chorea, spasticity, and epilepsy.

3811
(6.1%)

Spinocerebellar ataxia type 28

Ptosis

Autosomal dominant inheritance

Spinocerebellar ataxia type 28 (SCA28) is a very rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by juvenile onset, slowly progressive cerebellar ataxia due to Purkinje cell degeneration.

3811
(6.1%)

X-linked Charcot-Marie-Tooth disease type 3

Hearing impairment

X-linked recessive inheritance

X-linked Charcot-Marie-Tooth disease type 3 is a rare, genetic, peripheral sensorimotor neuropathy characterized by an X-linked recessive inheritance pattern and the childhood- to adolescent-onset of progressive, distal muscle weakness and atrophy (beginning in the lower extremities and then affecting the upper extremities), as well as distal, pansensory loss in the upper and lower extremities, pes cavus, and absent or reduced distal tendon reflexes. Pain and paresthesia are frequently the initial sensory symptoms. Spastic paraparesis (manifested by clasp-knife sign, hyperactive deep-tendon reflexes, and Babinski sign) has also been reported.

3811
(6.1%)

X-linked Charcot-Marie-Tooth disease type 5

Hearing impairment

Autosomal recessive inheritance X-linked recessive inheritance

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.

3811
(6.1%)

Cerebellar ataxia-hypogonadism syndrome

Hypogonadotropic hypogonadism

Autosomal recessive inheritance

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

3811
(6.1%)

Jackson-Weiss syndrome

Abnormal palate morphology

Autosomal dominant inheritance

Jackson-Weiss syndrome (JWS) is a rare genetic disorder characterized by foot malformations (tarsal and metatarsal fusions; short, broad, medially deviated great toes) and in some patients craniosynostosis with facial anomalies. Hands are normal in affected patients.