3811
(6.1%)

Crane-Heise syndrome

Cryptorchidism

Autosomal recessive inheritance

Crane-Heise syndrome is a very rare syndrome characterized by poorly mineralized calvarium, facial dysmorphism, vertebral abnormalities and absent clavicles.

3811
(6.1%)

FRAXE intellectual disability

Macrocephaly

X-linked inheritance X-linked recessive inheritance

FRAXE is a form of nonsyndromic X-linked mental retardation (NS-XLMR) characterized by mild intellectual deficit. FRAXE is the most common form of NS-XLMR.

3811
(6.1%)

Childhood-onset autosomal recessive slowly progressive spinocerebellar ataxia

Dysmetric saccades

Autosomal recessive inheritance

A rare, genetic, autosomal recessive cerebellar ataxia disease characterized by slowly progressive spinocerebellar ataxia developing during childhood, manifesting with gait and limb ataxia, postural tremor, dysarthria, sensory alterations (e.g. decreased vibration sense), eye movement anomalies (i.e. nystagmus, saccadic pursuit, oculomotor apraxia), upper and lower limb fasciculations, and hyperreflexia with Babinski signs. Brain imaging reveals cerebellar, pontine, vermian and medullar atrophy.

3811
(6.1%)

Eye defects-arachnodactyly-cardiopathy syndrome

Cleft palate

3811
(6.1%)

Symptomatic form of Coffin-Lowry syndrome in female carriers

Everted lower lip vermilion

3811
(6.1%)

Anophthalmia plus syndrome

Cleft palate

Autosomal recessive inheritance

A very rare multiple congenital anomaly syndrome characterized by the presence of anophthalmia or severe microphthalmia, cleft lip/palate, facial cleft and sacral neural tube defects, along with various additional anomalies including congenital glaucoma, iris coloboma, primary hyperplastic vitreous, hypertelorism, low-set ears, clinodactyly, choanal atresia/stenosis, dysgenesis of sacrum, tethering of spinal cord, syringomyelia, hypoplasia of corpus callosum, cerebral ventriculomegaly and endocrine abnormalities. An autosomal recessive inheritance has been suggested.

3811
(6.1%)

Fried syndrome

High palate

Fried syndrome is a rare X-linked mental retardation (XLMR) syndrome characterized by psychomotor delay, intellectual deficit, hydrocephalus, and mild facial anomalies.

3811
(6.1%)

Spinocerebellar ataxia type 19/22

Urinary incontinence

Autosomal dominant inheritance

Spinocerebellar ataxia type 19 (SCA19) is a very rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by mild cerebellar ataxia, cognitive impairment, low scores on the Wisconsin Card Sorting Test measuring executive function, myoclonus, and postural tremor.

3811
(6.1%)

Spinocerebellar ataxia type 12

Behavioral abnormality

Autosomal dominant inheritance

Spinocerebellar ataxia type 12 (SCA12) is a very rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by the presence of action tremor associated with relatively mild cerebellar ataxia. Associated pyramidal and extrapyramidal signs and dementia have been reported.

3811
(6.1%)

Infantile neuronal ceroid lipofuscinosis

Microcephaly

Infantile neuronal ceroid lipofuscinosis (INCL) is a form of neuronal ceroid lipofuscinosis (NCL; see this term) characterized by onset during the second half of the first year of life and rapid mental and motor deterioration leading to loss of all psychomotor abilities.

3811
(6.1%)

Corpus callosum agenesis-neuronopathy syndrome

Microcephaly

Autosomal recessive inheritance

Corpus callosum agenesis-neuronopathy syndrome is a neurodegenerative disorder characterized by severe progressive sensorimotor neuropathy beginning in infancy with resulting hypotonia, areflexia, amyotrophy and variable degrees of dysgenesis of the corpus callosum. Additional features include mild-to-severe intellectual and developmental delays, and psychiatric manifestations that include paranoid delusions, depression, hallucinations, and "autistic-like" features. Affected individuals are usually wheelchair restricted in the second decade of life and die in the third decade of life. The disease is inherited as an autosomal recessive trait.

3811
(6.1%)

Autosomal dominant spastic paraplegia type 8

Urinary urgency

Autosomal dominant inheritance

A pure or complex form of hereditary spastic paraplegia characterized by a childhood to adulthood onset of slowly progressive lower limb spasticity resulting in gait disturbances, hyperreflexia and extensor plantar responses, that may be associated with complicating signs, such as upper limb involvement, sensory neuropathy, ataxia (i.e. mild dysmetria, uncoordinated eye movement) and mild dysphagia. Additional symptoms, including urinary urgency and/or incontinence, muscle weakness, decreased vibration sense and mild muscular atrophy in lower extremities, may also be associated.

3811
(6.1%)

Spinocerebellar ataxia type 43

Hypometric saccades

Autosomal dominant inheritance

Spinocerebellar ataxia type 43 is a rare autosomal dominant cerebellar ataxia type I disorder characterized by late adult-onset of slowly progressive cerebellar ataxia, typically presenting with balance and gait disturbances, in association with axonal peripheral neuropathy resulting in reduced/absent deep tendon reflexes and sensory impairment. Lower limb pain and amyotrophy may be present, as well as various cerebellar signs, including dysarthria, nystagmus, hypometric saccades and tremor.

3811
(6.1%)

Chondrodysplasia-disorder of sex development syndrome

Male pseudohermaphroditism

Autosomal recessive inheritance

Chondrodysplasia - disorder of sex development is an extremely rare disorder of sex development (see this term), reported in only two siblings (one terminated in pregnancy) to date, characterized by the clinical features of 46,XY complete gonadal dysgenesis (see this term; normal external female genitalia, lack of pubertal development, primary amenorrhea, and hypergonadotrophic hypogonadism) in association with severe dwarfism with generalized chondrodysplasia (bell-shaped thorax, micromelia, brachydactyly). Other reported features in the live sibling included eye anomalies (hypoplastic irides, myopia, coloboma of optic discs), dysmorphic features (deep-set eyes, upslanting palpebral fissures, puffy eyelids, large ears and mouth, mild prognathism), muscular hypoplasia, mild intellectual deficiency and severe microcephaly with cerebellar vermis hypoplasia. An autosomal recessive inheritance has been suggested.

3811
(6.1%)

SIX2-related frontonasal dysplasia

Abnormality of the kidney

3811
(6.1%)

Axial spondylometaphyseal dysplasia

Hypertelorism

Autosomal recessive inheritance

Axial spondylometaphyseal dysplasia is a rare type of spondylometaphyseal dysplasia characterized by metaphyseal changes of the truncal-juxtatruncal bones associated with retinal dystrophy. Patients typically present progressive postnatal growth failure with rhizomelic shortening of the limbs, a deformed, hypoplastic thorax and retinitis pigmentosa or pigmentary retinal degeneration. Radiographic findings include short ribs with flared, cupped anterior ends, mild platyspondyly, lacy ilia and metaphyseal dysplasia of the proximal femora.

3811
(6.1%)

Ring chromosome Y syndrome

Male hypogonadism

Ring chromosome Y syndrome is a rare chromosome Y structural anomaly, with a highly variable phenotype, mostly characterized by short stature, partial to total gonadal failure, sexual infantilism, genital anomalies (e.g. ambiguous genitalia, hypospadias, cryptorchidism), and azoospermia or oligozoospermia. Additional reported features include speech delay, obesity, and acanthosis nigricans. Gender dysphoria and comorbid bipolar disorder have also been observed.

3811
(6.1%)

Rare non-syndromic intellectual disability

Microcephaly

Rare non-syndromic intellectual disability is a rare, hereditary, neurologic disease characterized by early-onset cognitive impairment as a sole disability. The disease may be associated with autism, epilepsy and neuromuscular deficits.

3811
(6.1%)

Autosomal dominant Charcot-Marie-Tooth disease type 2Y

Abnormality of the nervous system

Autosomal dominant inheritance

A rare, axonal hereditary motor and sensory neuropathy characterized by progressive distal muscle weakness and atrophy of variable onset and severity. Patients present with postural instability, gait and running difficulties, decreased deep tendon reflexes, foot deformities, fine motor impairment, and distal sensory impairment. Dysarthria, dysphagia, and mild cognitive and behavioral abnormalities have also been reported.

3811
(6.1%)

Adenylosuccinate synthetase-like 1-related distal myopathy

Reduced tendon reflexes

3811
(6.1%)

Frontotemporal dementia, right temporal atrophy variant

Behavioral abnormality

Right temporal lobar atrophy (RTLA) is an anatomic variant of frontotemporal dementia (FTD), characterized by behavioral dysfunction, personality changes, episodic memory loss, and prosopagnosia; attributable to an asymmetrical predominantly right-sided, frontotemporal atrophy.

3811
(6.1%)

Central areolar choroidal dystrophy

Retinopathy

Central areolar choroidal dystrophy (CACD) is a hereditary macular disorder, usually presenting between the ages of 30-60, characterized by a large area of atrophy in the centre of the macula and the loss or absence of photoreceptors, retinal pigment epithelium and choriocapillaris in this area, resulting in a progressive decrease in visual acuity.

3811
(6.1%)

Weissenbacher- Zweymuller syndrome

Glossoptosis

Weissenbacher-Zweymuller syndrome (WZS) is characterized by short stature at birth, neonatal micrognathia, cleft palate, rhizomelic chondrodysplasia with 'dumbbell' shaped arm and leg bones, hypertelorism and vertebral coronal clefts.

3811
(6.1%)

Myoclonic epilepsy of infancy

Aggressive behavior

3811
(6.1%)

PRKAR1B-related neurodegenerative dementia with intermediate filaments

Inappropriate behavior

PRKAR1B-related neurodegenerative dementia with intermediate filaments is a rare, genetic neurodegenerative disease characterized by dementia and mild parkinsonism with poor levodopa response. Presenting clinical manifestations are memory problems, short attention span, disorientation, language impairment, rigidity, bradykinesia, postural instability and behavioral changes, including apathy, anxiety and delusions.

3811
(6.1%)

Myoclonic-astastic epilepsy

Aggressive behavior

A rare epilepsy syndrome of childhood characterized by the occurrence of multiple different seizure types including myoclonic-astatic, generalized tonic-clonic and absence seizures, usually in previously healthy children.

3811
(6.1%)

Holoprosencephaly-craniosynostosis syndrome

Brachycephaly

Holoprosencephaly-craniosynostosis syndrome is a rare developmental defect during embryogenesis syndrome characterized by the association of primary craniosynostosis (usually involving the coronal and metopic sutures) with holoprosencephaly (ranging from alobar to, most commonly, semilobar) and various skeletal anomalies (typically, hand and feet anomalies including fifth digit clinodactyly, hypoplastic phalanges and cone-shaped epiphyses, small vertebral bodies, scoliosis, coxa valga and/or flexion deformities of hips). Craniofacial asymmetry, microcephaly, brachy/plagiocephaly, short stature and psychomotor delay are additional common features.

3811
(6.1%)

Leukoencephalopathy-spondylometaphyseal dysplasia syndrome

Anteverted nares

X-linked recessive inheritance

A disorder that has been reported in four men from a three-generation family. Onset manifests by spastic paraplegia at the age of 2, followed by tremor, ataxia, optic atrophy, and spastic tetraparesis. Transmission is X-linked and the gene responsible of the disease may be located at Xq25-q27.

3811
(6.1%)

X-linked intellectual disability-cerebellar hypoplasia syndrome

Cryptorchidism

X-linked recessive inheritance X-linked dominant inheritance

X-linked intellectual deficit-cerebellar hypoplasia, also known as OPHN1 syndrome, is a rare syndromic form of cerebellar dysgenesis characterized by moderate to severe intellectual deficit and cerebellar abnormalities.

3811
(6.1%)

3q27.3 microdeletion syndrome

Narrow mouth

3q27.3 microdeletion syndrome is a rare chromosomal anomaly syndrome, resulting from the partial deletion of the long arm of chromosome 3, characterized by mild to severe intellectual disability, neuropsychiatric disorders of the psychotic and dysthymic spectrum, mild distinctive facial dysmorphism (incl. slender face, deep-set eyes, high nasal bridge with a hooked nose, small, low- set ears, short philtrum, small mouth with thin upper lip, prognathism) and a marfanoid habitus.

3811
(6.1%)

Autosomal dominant spastic paraplegia type 19

Urinary urgency

Autosomal dominant inheritance

A pure form of hereditary spastic paraplegia characterized by a slowly progressive and relatively benign spastic paraplegia presenting in adulthood with spastic gait, lower limb hyperreflexia, extensor plantar responses, bladder dysfunction (urinary urgency and/or incontinence), and mild sensory and motor peripheral neuropathy.

3811
(6.1%)

Metaphyseal acroscyphodysplasia

Epicanthus

Autosomal recessive inheritance

Metaphyseal acroscyphodysplasia is an extremely rare form of metaphyseal dysplasia characterized by the distinctive radiological sign of cone-shaped upper tibial and lower femoral epiphyses embedded in large cup-shaped metaphyses, associated with short stature and micromelia. Upper limb involvement includes brachydactyly and phalangeal and metacarpal cone-shaped epiphyses. The association of metaphyseal acroscyphodysplasia with psychomotor delay and alopecia has also been reported in some cases.

3811
(6.1%)

Early-onset progressive encephalopathy-spastic ataxia-distal spinal muscular atrophy syndrome

Optic atrophy

3811
(6.1%)

Craniosynostosis, Herrmann-Opitz type

Cleft palate

Craniosynostosis, Herrmann-Opitz type is a rare bone development disorder characterized by intellectual disability, short stature, turribrachycephaly, facial dysmorphism (i.e. severe hypertelorism, hypoplasia of supraorbital ridges, abnormal ears, and micrognathia), bony defects of the occiput, and digital anomalies (incl. syndactyly, oligodactyly, and/or brachydactyly). Urethral atresia has also been reported. There have been no further descriptions in the literature since 1987.

3811
(6.1%)

Spinocerebellar ataxia type 27

Strabismus

Autosomal dominant inheritance Heterogeneous

Spinocerebellar ataxia type 27 (SCA27) is a very rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by early-onset tremor, dyskinesia, and slowly progressive cerebellar ataxia.

3811
(6.1%)

Eiken syndrome

Broad palm

Autosomal recessive inheritance

A rare, genetic, primary bone dysplasia syndrome characterized by multiple epiphyseal dysplasia, severely delayed ossification (mainly of the epiphyses, pubic symphysis, hands and feet), abnormal modeling of the bones in hands and feet, abnormal pelvis cartilage persistence, and mild growth retardation. Calcium, phosphate and vitamin D serum levels are typically within normal range, while parathyroid hormone serum levels are normal to slighly elevated. Oligodontia has been rarely associated.

3811
(6.1%)

Autosomal dominant spastic paraplegia type 38

Urinary incontinence

Autosomal dominant inheritance

A complex hereditary spastic paraplegia characterized by mild to severe lower limbs spasticity, hyperreflexia, extensor plantar responses, pes cavus and significant wasting and weakness of the small hand muscles. Impaired vibration sensation, temporal lobe epilepsy and cognitive dysfunction were also reported.

3811
(6.1%)

Leydig cell hypoplasia

Male hypogonadism

3811
(6.1%)

Lethal osteosclerotic bone dysplasia

Gingival fibromatosis

Autosomal recessive inheritance

A rare disorder defined by generalized osteosclerosis with periosteal bone formation, characteristic facial dysmorphism, brain abnormalities including intracerebral calcifications, and neonatal lethal course.

3811
(6.1%)

Spondyloepimetaphyseal dysplasia congenita, Strudwick type

Cleft palate

Autosomal dominant inheritance

Spondyloepimetaphyseal dysplasia congenita, Strudwick type is characterized by disproportionate short stature from birth (with a very short trunk and shortened limbs) and skeletal abnormalities (lordosis, scoliosis, flattened vertebrae, pectus carinatum, coxa vara, clubfoot, and abnormal epiphyses or metaphyses).