3811
(6.1%)

1p21.3 microdeletion syndrome

Wide mouth

1p21.3 microdeletion syndrome is an extremely rare chromosomal anomaly characterized by severe speech and language delay, intellectual deficiency, autism spectrum disorder(see this term).

3811
(6.1%)

X-linked progressive cerebellar ataxia

Nystagmus

X-linked inheritance X-linked recessive inheritance

3811
(6.1%)

46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome

Hypoplasia of the uterus

Autosomal recessive inheritance

46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome is a rare, genetic, developmental defect during embryogenesis disorder characterized by partial (unilateral testis, persistence of Müllerian duct structures) or complete (streak gonads only) gonadal dysgenesis, usually manifesting with primary amenorrhea in individuals with female phenotype but 46,XY karyotype, and sensorimotor dysmyelinating minifascicular polyneuropathy, which presents with numbness, weakness, exercise-induced muscle cramps, sensory disturbances and reduced/absent deep tendon reflexes. Germ cell tumors (seminoma, dysgerminoma, gonadoblastoma) may develop from the gonadal tissue.

3811
(6.1%)

Spondyloepimetaphyseal dysplasia, Irapa type

Pectus carinatum

Autosomal recessive inheritance

Spondyloepimetaphyseal dysplasia, Irapa type is characterized by disproportionate short-trunked short stature, pectus carinatum, short arms, short and broad hands, short metatarsals, flat and broad feet, coxa vara, genu valgum, osteoarthritis, arthrosis and moderate-to-serious gait impairment.

3811
(6.1%)

Spondylometaphyseal dysplasia-cone-rod dystrophy syndrome

Astigmatism

Autosomal recessive inheritance

Spondylometaphyseal dysplasia-cone-rod dystrophy syndrome is characterised by the association of spondylometaphyseal dysplasia (marked by platyspondyly, shortening of the tubular bones and progressive metaphyseal irregularity and cupping), with postnatal growth retardation and progressive visual impairment due to cone-rod dystrophy. So far, it has been described in eight individuals. Transmission appears to be autosomal recessive.

3811
(6.1%)

Spondylometaphyseal dysplasia, Kozlowski type

High forehead

Autosomal dominant inheritance

Spondylometaphyseal dysplasia, Kozlowski type is characterized by short stature (short-trunk dwarfism), scoliosis, metaphyseal abnormalities in the femur (prominent in the femoral neck and trochanteric area), coxa vara and generalized platyspondyly.

3811
(6.1%)

Cole-Carpenter syndrome

Turricephaly

An extremely rare form of bone dysplasia characterized by the features of osteogenesis imperfecta such as bone fragility associated with multiple fractures, bone deformities (metaphyseal irregularities and bowing of the long bones) and blue sclera, in association with growth failure, craniosynostosis, hydrocephalus, ocular proptosis, and distinctive facial features (e.g. frontal bossing, midface hypoplasia, and micrognathia).

3811
(6.1%)

Dysplasia epiphysealis hemimelica

Syndactyly

3811
(6.1%)

Dentinogenesis imperfecta

Hydrocephalus

Dentinogenesis imperfecta (DGI) is a hereditary dentin defect (see this term) characterized by abnormal dentin structure resulting in abnormal tooth development.

3811
(6.1%)

Autosomal recessive spastic paraplegia type 11

Cataract

Autosomal recessive inheritance

A complex hereditary spastic paraplegia characterized by progressive lower limbs weakness and spasticity, upper limbs weakness, dysarthria, hypomimia, sphincter disturbances, peripheral neuropathy, learning difficulties, cognitive impairment and dementia. Magnetic resonance imaging shows thin corpus callosum, cerebral atrophy, and periventricular white matter changes.

3811
(6.1%)

Otopalatodigital syndrome type 1

Cleft palate

X-linked dominant inheritance

A disorder that is the mildest form of otopalatodigital syndrome spectrum disorder, and is characterized by a generalized skeletal dysplasia, mild intellectual disability, conductive hearing loss, and typical facial anomalies.

3811
(6.1%)

Distal monosomy 9p

Hypospadias

Distal monosomy 9p is a rare chromosomal anomaly syndrome, resulting from a partial deletion of the short arm of chromosome 9, with a highly variable phenotype typically characterized by intellectual disability, craniofacial dysmorphism (trigonocephaly, upslanting palpebral fissures, hypoplastic supraorbital ridges), abnormal digits (long middle phalanges with short distal phalanges), as well as frequent association with genitourinary abnormalities (cryptorchidism, hypospadias, ambiguous genitalia, 46,XY testicular dysgenesis). Congenital hypothyroidism and cardiovascular defects have been reported in some cases. Patients present an increased risk for gonadoblastoma.

3811
(6.1%)

Autosomal recessive spastic paraplegia type 55

Strabismus

Autosomal recessive inheritance

Autosomal recessive spastic paraplegia type 55 (SPG 55) is a rare, complex type of hereditary spastic paraplegia characterized by childhood onset of progressive spastic paraplegia associated with optic atrophy (with reduced visual acuity and central scotoma), ophthalmoplegia, reduced upper-extremity strength and dexterity, muscular atrophy in the lower extremities, and sensorimotor neuropathy. SPG55 is caused by mutations in the C12ORF65 gene (12q24.31) encoding probable peptide chain release factor C12orf65, mitochondrial.

3811
(6.1%)

Atypical juvenile parkinsonism

Hypomimic face

A complex form of young-onset Parkinson disease that manifests with pyramidal signs, eye movement abnormalities, psychiatric manifestations (depression, anxiety, drug-induced psychosis, and impulse control disorders), intellectual disability, and other neurological symptoms (such as ataxia and epilepsy) along with classical parkinsonian symptoms.

3811
(6.1%)

X-linked intellectual disability, Najm type

Microcephaly

X-linked dominant inheritance

Najm type X-linked intellectual deficit is a rare cerebellar dysgenesis syndrome characterized by variable clinical manifestations ranging from mild intellectual deficit with or without congenital nystagmus, to severe cognitive impairment associated with cerebellar and pontine hypoplasia/atrophy and abnormalities of cortical development.

3811
(6.1%)

Atelosteogenesis type III

High palate

Autosomal dominant inheritance

A rare skeletal dysplasia characterized by short limbs dysmorphic facies and diagnostic radiographic findings.

3811
(6.1%)

Autosomal recessive spastic paraplegia type 78

Neurogenic bladder

3811
(6.1%)

2q24 microdeletion syndrome

Cleft palate

2q24 microdeletion syndrome is a chromosomal anomaly consisting of a partial long arm deletion of chromosome 2 and characterized clinically by a wide range of manifestations (depending on the specific region deleted) which can include seizures, microcephaly, dysmorphic features, cleft palate, eye abnormalities (coloboma, cataract and microphthalmia), growth retardation, failure to thrive, heart defects, limb anomalies, developmental delay and autism.

3811
(6.1%)

Juvenile Huntington disease

Behavioral abnormality

Juvenile Huntington disease (JHD) is a form of Huntington disease (HD; see this term), characterized by onset of signs and symptoms before 20 years of age.

3811
(6.1%)

Craniometaphyseal dysplasia

Hydrocephalus

Craniometaphyseal dysplasia (CMD) is a very rare genetic bone disease characterized by progressive diffuse hyperostosis of cranial bones causing facial dysmorphism and functional repercussions, and metaphyseal widening of long bones.

3811
(6.1%)

Laurin-Sandrow syndrome

Cryptorchidism

Autosomal dominant inheritance

Laurin-Sandrow syndrome (LSS) is characterised by complete polysyndactyly of the hands, mirror feet and nose anomalies (hypoplasia of the nasal alae and short columella), often associated with ulnar and/or fibular duplication (and sometimes tibial agenesis). It has been described in less than 20 cases. Some cases with the same clinical signs but without nasal defects have also been reported, and may represent the same entity. The etiology of LSS is unknown. Different modes of inheritance have been suggested.

3811
(6.1%)

Female restricted epilepsy with intellectual disability

Behavioral abnormality

X-linked inheritance

Female restricted epilepsy with intellectual disability is a rare X-linked epilepsy syndrome characterized by febrile or afebrile seizures (mainly tonic-clonic, but also absence, myoclonic, and atonic) starting in the first years of life and, in most cases, developmental delay and intellectual disability of variable severity. Behavioral disturbances (e.g. autistic features, hyperactivity, and aggressiveness) are also frequently associated. This disease affects exclusively females, with male carriers being unaffected, despite an X-linked inheritance.

3811
(6.1%)

Autosomal recessive spastic paraplegia type 9B

Urinary retention

Autosomal recessive inheritance

3811
(6.1%)

Charcot-Marie-Tooth disease-deafness-intellectual disability syndrome

Decreased nerve conduction velocity

Autosomal dominant inheritance Autosomal recessive inheritance

Charcot-Marie-Tooth disease-deafness-intellectual disability syndrome is a rare demyelinating hereditary motor and sensory neuropathy characterized by early-onset, slowly progressive, distal muscular weakness and atrophy with no sensory impairment, congenital sensorineural deafness and mild intellectual disability (with absence of normal speech development). The absence of large myelinated fibers on sural nerve biopsy is equally characteristic of the disease.

3811
(6.1%)

Neurofaciodigitorenal syndrome

Cryptorchidism

Autosomal recessive inheritance

Neurofaciodigitorenal syndrome is a rare multiple developmental anomalies syndrome characterized by neurological abnormalities (including megalencephaly, hypotonia, intellectual disability, abnormal EEG), dysmorphic facial features (high prominent forehead, grooved nasal tip, ptosis, ear anomalies) and acrorenal defects (such as triphalangism, broad halluces, unilateral renal agenesis). Additionally, intrauterine growth restriction, short stature and congenital heart defects may be associated. There have been no further descriptions in the literature since 1997.

3811
(6.1%)

Dyggve-Melchior-Clausen disease

Microcephaly

Autosomal recessive inheritance

Dyggve-Melchior-Clausen disease (DMC) is a rare skeletal disorder belonging to the group of spondyloepimetaphyseal dysplasias (see this term).

3811
(6.1%)

Autosomal recessive cerebellar ataxia-pyramidal signs-nystagmus-oculomotor apraxia syndrome

Ptosis

A rare, genetic, slowly progressive neurodegenerative disease characterized by delayed psychomotor development beginning in infancy, mild to profound intellectual disability, gait and stance ataxia, pyramidal signs (hyperreflexia, extensor plantar responses), dysarthria, and ocular abnormalities (e.g. nystagmus, oculomotor apraxia, abduction deficits, esotropia, ptosis). Brain imaging reveals progressive, generalized cerebellar atrophy, mild ventriculomegaly and, in some, retrocerebellar cysts.

3811
(6.1%)

Temtamy syndrome

Abnormal palate morphology

Autosomal recessive inheritance

Temtamy syndrome is a very rare congenital genetic neurological disorder characterized by agenesis/hypoplasia of corpus callosum with developmental abnormalities, ocular disorders, and variable craniofacial and skeletal abnormalities.

3811
(6.1%)

Proximal symphalangism

Nephropathy

Proximal symphalangism is a very rare, genetic bone disorder characterized by ankylosis of the proximal interphalangeal joints, carpal and tarsal bone fusion, and conductive hearing loss in some patients.

3811
(6.1%)

Severe intellectual disability-progressive spastic diplegia syndrome

Thin upper lip vermilion

Autosomal dominant inheritance

Severe intellectual disability-progressive spastic diplegia syndrome is a rare, genetic, syndromic intellectual disability disorder characterized by intellectual disability, significant motor delay, severe speech impairment, early-onset truncal hypotonia with progressive distal hypertonia/spasticity, microcephaly, and behavioral anomalies (autistic features, aggression or auto-aggressive behavior, sleep disturbances). Variable facial dysmorphism includes broad nasal tip with small alae nasi, long and/or flat philtrum, thin upper lip vermillion. Visual impairment (strabismus, hyperopia, myopia) is commonly associated.

3811
(6.1%)

Spinocerebellar ataxia type 10

Urinary urgency

Autosomal dominant inheritance Genetic anticipation

Spinocerebellar ataxia type 10 (SCA10) is a subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by slowly progressive cerebellar syndrome and epilepsy, sometimes mild pyramidal signs, peripheral neuropathy and neuropsychological disturbances.

3811
(6.1%)

Dentatorubral pallidoluysian atrophy

Ophthalmoparesis

Autosomal dominant inheritance Genetic anticipation

A rare subtype of autosomal dominant cerebellar ataxia type I characterized by involuntary movements, ataxia, epilepsy, mental disorders, cognitive decline and prominent anticipation.

3811
(6.1%)

Autosomal recessive spastic paraplegia type 46

Urinary incontinence

Autosomal recessive inheritance

Autosomal recessive spastic paraplegia type 46 (SPG46) is a rare, complex type of hereditary spastic paraplegia characterized by an onset, in infancy or childhood, of the typical signs of spastic paraplegia (i.e. spastic gait and weakness of the lower limbs) associated with a variety of additional manifestations including upper limb spasticity and weakness, pseudobulbar dysarthria, bladder dysfunction, cerebellar ataxia, cataracts, and cognitive impairment that can progress to dementia. Brain imaging may show thinning of the corpus callosum and mild atrophy of the cerebrum and cerebellum. SPG46 is due to mutations in the GBA2 gene (9p13.2) encoding non-lysosomal glucosylceramidase.

3811
(6.1%)

Autosomal spastic paraplegia type 58

Microcephaly

Autosomal recessive inheritance

Autosomal recessive spastic paraplegia type 58 is a rare, complex subtype of hereditary spastic paraplegia characterized by variable onset of slowly progressive lower limb spasticity and weakness and prominent cerebellar ataxia, associated with gait disturbances, dysarthria, increased deep tendon reflexes and extensor plantar responses. Additional features may include involuntary movements (i.e. clonus, tremor, fasciculations, chorea), decreased vibration sense, oculomotor abnormalities (e.g. nystagmus) and distal amyotrophy in the upper and lower limbs.

3811
(6.1%)

Autosomal dominant optic atrophy and cataract

Visual impairment

Autosomal dominant inheritance

A form of autosomal dominant optic atrophy characterized by an early and bilateral optic atrophy leading to insidious visual loss of variable severity, followed by a late anterior and/or posterior cortical cataract. Additional features include sensorineural hearing loss and neurological signs such as tremor, extrapyramidal rigidity and absence of deep tendon reflexes. It is caused by mutations in the OPA3 gene (19q13.32).

3811
(6.1%)

Pituitary carcinoma

Microcephaly

3811
(6.1%)

6q25 microdeletion syndrome

Hydronephrosis

6q25 microdeletion syndrome is a recently described syndrome characterized by developmental delay, facial dysmorphism and hearing loss.

3811
(6.1%)

Ataxia-telangiectasia-like disorder

Microcephaly

3811
(6.1%)

Mietens syndrome

Microcephaly

Autosomal recessive inheritance

Mietens syndrome is a very rare syndrome consisting of corneal opacity, nystagmus, strabismus, flexion contracture of the elbows with dislocation of the head of the radius and abnormally short ulnae and radii.

3811
(6.1%)

Generalized epilepsy with febrile seizures-plus

Autism

Generalized epilepsy with febrile seizures plus (GEFS+) is a familial epilepsy syndrome in which family members display a seizure disorder from the GEFS+ spectrum which ranges from simple febrile seizures (FS) to the more severe phenotype of myoclonic-astatic epilepsy (MAE) or Dravet syndrome (DS) (see these terms).