3811
(6.1%)

Hypoplastic tibiae-postaxial polydactyly syndrome

Depressed nasal tip

Hypoplastic tibia-polydactyly syndrome is a very rare congenital malformation syndrome characterized by bilateral hypoplasia of the tibia with polydactyly of the feet and hands.

3811
(6.1%)

Microcephalic osteodysplastic dysplasia, Saul-Wilson type

Microcephaly

Microcephalic osteodysplastic dysplasia, Saul-Wilson type is a skeletal dysplasia characterized by a distinct facial phenotype, short stature, brachydactyly, clubfoot deformities, cataracts, and microcephaly. It has been described in four patients. Facial features include frontal bossing with a depression over the metopic suture, a narrow nasal root with a beaked nose, and midfacial hypoplasia with prominent eyes. Characteristic radiographic findings are observed (irregularities of the vertebral bodies, hypoplasia of the odontoid process, short phalanges, coning several epiphyses etc.).

3811
(6.1%)

Mesomelic dysplasia, Kantaputra type

Abnormality of the ribs

Autosomal dominant inheritance

Mesomelic dysplasia Kantaputra type (MDK) is a rare skeletal disease characterized by symmetric shortening of the middle segments of limbs and short stature.

3811
(6.1%)

Growth delay due to insulin-like growth factor I resistance

Everted lower lip vermilion

Autosomal dominant inheritance Autosomal recessive inheritance

Growth delay due to IGF-I resistance is characterised by variable intrauterine and postnatal growth retardation and elevated serum IGF-I levels. Addition features include variable degrees of intellectual deficit, microcephaly and dysmorphism (broad nasal bridge and tip, smooth philtrum, thin upper and everted lower lips, short fingers, clinodactyly, wide-set nipples and pectus excavatum).

3811
(6.1%)

Atkin-Flaitz syndrome

Macroorchidism

X-linked recessive inheritance X-linked dominant inheritance

A rare syndrome characterised by moderate to severe intellectual deficit, short stature, macrocephaly, and characteristic facies. It has been described in 11 males and three females from three successive generations of the same family. The males also presented with postpubertal macroorchidism. Transmission is X-linked.

3811
(6.1%)

Autosomal recessive spastic paraplegia type 53

Microcephaly

Autosomal recessive inheritance

Autosomal recessive spastic paraplegia type 53 (SPG53) is a very rare, complex type of hereditary spastic paraplegia characterized by early-onset spastic paraplegia (with spasticity in the lower extremities that progresses to the upper extremities) associated with developmental and motor delay, mild to moderate cognitive and speech delay, skeletal dysmorphism (e.g. kyphosis and pectus), hypertrichosis and mildly impaired vibration sense. SPG53 is due to mutations in the VPS37A gene (8p22) encoding vacuolar protein sorting-associated protein 37A.

3811
(6.1%)

Autosomal dominant spastic paraplegia type 13

Urinary urgency

Autosomal dominant inheritance

A rare hereditary spastic paraplegia characterized by progressive spastic paraplegia with pyramidal signs in the lower limbs, decreased vibration sense, and increased reflexes in the upper limbs.

3811
(6.1%)

Autosomal recessive spastic paraplegia type 44

Sensorineural hearing impairment

Autosomal recessive inheritance

Autosomal recessive spastic paraplegia type 44 (SPG44) is a very rare, complex form of hereditary spastic paraplegia characterized by a late-onset, slowly progressive spastic paraplegia associated with mild ataxia and dysarthria, upper extremity involvement (i.e. loss of finger dexterity, dysmetria), and mild cognitive impairment, without the presence of nystagmus. A hypomyelinating leukodystrophy and thin corpus callosum is observed in all cases and psychomotor development is normal or near normal. SPG44 is caused by mutations in the GJC2 gene (1q41-q42) encoding the gap junction gamma-2 protein.

3811
(6.1%)

X-linked non progressive cerebellar ataxia

Strabismus

X-linked recessive inheritance

X-linked non progressive cerebellar ataxia is a rare hereditary ataxia characterized by delayed early motor development, severe neonatal hypotonia, non-progressive ataxia and slow eye movements, presenting normal cognitive abilities and absence of pyramidal signs. Frequently patients also manifest intention tremor, mild dysphagia, and dysarthria. Brain MRI reveals global cerebellar atrophy with absence of other malformations or degenerations of the central and peripheral nervous systems.

3811
(6.1%)

Autosomal recessive spastic ataxia-optic atrophy-dysarthria syndrome

Movement abnormality of the tongue

Autosomal recessive inheritance

A rare, genetic, autosomal recessive spastic ataxia disease characterized by onset in early childhood of spastic paraparesis, cerebellar ataxia, dysarthria and optic atrophy.

3811
(6.1%)

Autosomal recessive spastic paraplegia type 75

Astigmatism

Autosomal recessive inheritance

Autosomal recessive spastic paraplegia type 75 is a rare, complex hereditary spastic paraplegia characterized by an early onset and slow progression of spastic paraplegia associated with cerebellar signs, nystagmus, peripheral neuropathy, extensor plantar responses and borderline to mild intellectual disability. Additional features of hypo- or areflexia, mild upper limb involvement and significant visual impairment (optic atrophy, vision loss, astigmatism) have been reported.

3811
(6.1%)

Aniridia-renal agenesis-psychomotor retardation syndrome

Unilateral renal agenesis

Autosomal recessive inheritance

An extremely rare syndrome reported in two siblings of non consanguineous parents that is characterized by the association of ocular abnormalities (partial aniridia, congenital glaucoma, telecanthus) with frontal bossing, hypertelorism, unilateral renal agenesis and mild psychomotor delay. There have been no further descriptions in the literature since 1974.

3811
(6.1%)

Isolated optic nerve hypoplasia/aplasia

Vesicoureteral reflux

Autosomal dominant inheritance

3811
(6.1%)

Autosomal recessive spastic ataxia with leukoencephalopathy

Urinary urgency

Autosomal recessive inheritance

A rare, genetic, autosomal recessive spastic ataxia disease characterized by cerebellar ataxia, spasticity, cerebellar (and in some cases cerebral) atrophy, dystonia, and leukoencephalopathy.

3811
(6.1%)

Osteosclerosis-developmental delay-craniosynostosis syndrome

Brachycephaly

This newly described syndrome is characterized by osteosclerosis, developmental delay and craniosynostosis (see this term).

3811
(6.1%)

Multiple epiphyseal dysplasia, Al-Gazali type

Macrocephaly

Autosomal recessive inheritance

Multiple epiphyseal dysplasia, Al-Gazali type is a skeletal dysplasia characterized by multiple epiphyseal dysplasia (see this term), macrocephaly and facial dysmorphism.

3811
(6.1%)

X-linked Charcot-Marie-Tooth disease type 2

Sensory neuropathy

X-linked recessive inheritance

X-linked Charcot-Marie-Tooth disease type 2 is a rare, genetic, peripheral sensorimotor neuropathy characterized by an X-linked recessive inheritance pattern and the infantile- to childhood-onset of progressive, distal muscle weakness and atrophy (more prominent in the lower extremities than in the upper extremities), pes cavus, and absent tendon reflexes. Sensory impairment and intellectual disability has been reported in some individuals.

3811
(6.1%)

Myoclonus-dystonia syndrome

Torticollis

Myoclonus-dystonia syndrome (MDS) is a rare movement disorder characterized by mild to moderate dystonia along with 'lightning-like' myoclonic jerks.

3811
(6.1%)

Pontocerebellar hypoplasia type 2

Microcephaly

Pontocerebellar hypoplasia type 2 (PCH2) is the most common subtype of pontocerebellar hypoplasia (see this term) characterized by neonatal onset and a lack of voluntary motor development and later progressive microencephaly, generalized clonus, development of chorea and spasticity. The majority of patients will not reach puberty.

3811
(6.1%)

Distal hereditary motor neuropathy type 5

Spastic paraplegia

3811
(6.1%)

Craniofacial-deafness-hand syndrome

Narrow mouth

Autosomal dominant inheritance

Craniofacial-deafness-hand syndrome (CDHS) is an autosomal dominant disorder, described in one family to date, characterized by characteristic facial features (flat facial profile with normal calvarium, hypertelorism, small downslanting palpebral fissures, hypoplastic nose with button tip and slitlike nares, small ''pursed'' mouth), profound sensorineural deafness, and ulnar deviations and contractures of the hand. CDHS is thought to be an allelic variant of Waardenburg syndrome (see this term) that can be distinguished from the latter by its imaging findings and distinct facial features.

3811
(6.1%)

Autosomal recessive spastic paraplegia type 43

Spasticity

Autosomal recessive inheritance

Autosomal recessive spastic paraplegia type 43 is a rare, complex hereditary spastic paraplegia characterized by a childhood to adolescent onset of progressive lower limb spasticity, associated with mild to severe gait disturbances, extensor plantar responses, muscle weakness and severe distal atrophy, frequently with upper limb involvement. Additional features may include joint contractures, distal sensory loss and brisk or absent deep tendon reflexes. Other signs, such as depression, memory loss, optic atrophy (with vision loss) and brain iron deposition (revealed by brain imagery), have also been reported.

3811
(6.1%)

Rhizomelic dysplasia, Patterson-Lowry type

Epicanthus

Autosomal recessive inheritance

Rhizomelic dysplasia, Patterson-Lowry type is a rare primary bone dysplasia characterized by short stature, severe rhizomelic shortening of the upper limbs associated with specific malformations of humeri (including marked widening and flattening of proximal metaphyses, medial flattening of the proximal epiphyses, and lateral bowing with medial cortical thickening of the proximal diaphyses), marked coxa vara with dysplastic femoral heads and brachimetacarpalia.

3811
(6.1%)

Autosomal dominant spastic paraplegia type 42

Seizure

Autosomal dominant inheritance

A pure form of hereditary spastic paraplegia characterized by slowly progressive spastic paraplegia of lower extremities with an age of onset ranging from childhood to adulthood and patients presenting with spastic gait, increased tendon reflexes in lower limbs, extensor plantar response, weakness and atrophy of lower limb muscles and, in rare cases, pes cavus. No abnormalities are noted on magnetic resonance imaging.

3811
(6.1%)

Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome

Sensorineural hearing impairment

3811
(6.1%)

Metaphyseal chondrodysplasia, Spahr type

Abnormality of the dentition

Autosomal recessive inheritance

A rare, genetic, primary bone dysplasia disease characterized by usually moderate, postnatal short stature, progressive genu vara deformity, a waddling gait, and radiological signs of metaphyseal dysplasia (i.e. irregular, sclerotic and widened metaphyses), in the absence of biochemical abnormalities suggestive of rickets disease. Intermittent knee pain, lordosis, and delayed motor development may also occasionally be associated.

3811
(6.1%)

Spinocerebellar ataxia type 14

Gaze-evoked nystagmus

Autosomal dominant inheritance

Spinocerebellar ataxia type 14 (SCA14) is a rare mild subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by slowly progressive ataxia, dysarthria and nystagmus.

3811
(6.1%)

Spinocerebellar ataxia type 37

Sensorineural hearing impairment

Autosomal dominant inheritance

Spinocerebellar ataxia type 37 (SCA37) is a subtype of autosomal dominant cerebellar ataxia type 1 (ADCA type 1; see this term), characterized by a cerebellar syndrome along with altered vertical eye movements.

3811
(6.1%)

3q13 microdeletion syndrome

Cryptorchidism

Autosomal dominant inheritance

3q13 microdeletion syndrome is a rare chromosomal anomaly syndrome resulting from a partial deletion of the long arm of chromosome 3. Phenotype can be highly variable, but it is primarily characterized by significant developmental delay, postnatal growth above the mean, muscular hypotonia and distinctive facial features (such as broad and prominent forehead, hypertelorism, epicantic folds, anti-mongloid slanted eyes, ptosis, short philtrum, protruding lips with a full lower lip, high arched palate). Abnormal hypoplastic male genitalia and skeletal abnormalities are frequently present.

3811
(6.1%)

Autosomal recessive spastic paraplegia type 76

Functional abnormality of the bladder

Autosomal recessive inheritance

Autosomal recessive spastic paraplegia type 76 is a rare, complex hereditary spastic paraplegia characterized by adult onset slowly progressive, mild to moderate lower limb spasticity and hyperreflexia, resulting in gait disturbances, commonly associated with upper limb hyperreflexia and dysarthria. Foot deformities (usually pes cavus) and extensor plantar responses are also frequent. Additional features may include ataxia, lower limb weakness/amyotrophy, abnormal bladder function, distal sensory loss and mild intellectual deterioration.

3811
(6.1%)

Ataxia-deafness-intellectual disability syndrome

Abnormal palate morphology

Autosomal recessive inheritance X-linked recessive inheritance

This syndrome is characterised by progressive ataxia beginning during childhood, deafness and intellectual deficit.

3811
(6.1%)

Partial androgen insensitivity syndrome

Azoospermia

X-linked recessive inheritance

A disorder of sex development (DSD) distinct from complete AIS (CAIS) characterized by the presence of abnormal genital development in a 46,XY individual with normal testis development and partial responsiveness to age-appropriate levels of androgens.

3811
(6.1%)

Langer mesomelic dysplasia

Gonadal dysgenesis

Autosomal recessive inheritance

A rare disorder characterized by severe disproportionate short stature with mesomelic and rhizomelic shortening of the upper and lower limbs.

3811
(6.1%)

Infantile-onset autosomal recessive nonprogressive cerebellar ataxia

Delayed speech and language development

Autosomal recessive inheritance

A rare, genetic, autosomal recessive cerebellar ataxia disease characterized by nonprogressive cerebellar ataxia, with onset in infancy, manifesting with delayed motor and speech development, gait ataxia, dysmetria, hypotonia, increased deep tendon reflexes, and dysarthria. Additional variable manifestations include moderate nystagmus on lateral gaze, mild spasticity, intention tremor, short stature and pes planus. Brain imaging reveals cerebellar vermis atrophy.

3811
(6.1%)

Hemiparkinsonism-hemiatrophy syndrome

Depressivity

Hemiparkinsonism-hemiatrophy syndrome is a rare parkinsonian disorder characterized by unilateral body atrophy and slowly progressive, ipsilateral, hemiparkinsonian signs (bradykinesia, rigidity, and tremor). Patients typically present with unilateral, action-induced dystonia, in upper or lower limbs, that progresses and becomes bilateral or with tremor which occurs predominantly at rest and progresses to hemiparkinsonism. Scoliosis, scapular winging, raised shoulders, brisk reflexes and extensor plantar responses are frequently associated.

3811
(6.1%)

Autosomal recessive spastic paraplegia type 56

Visual impairment

Autosomal recessive inheritance

A rare form of hereditary spastic paraplegia characterized by delayed walking, toe walking, unsteady and spastic gait, hyperreflexia of the lower limbs, and extensor plantar responses. Upper limbs spasticity and dystonia, subclinical axonal neuropathy, cognitive impairment and intellectual disability have also been associated.

3811
(6.1%)

Verloove Vanhorick-Brubakk syndrome

Cryptorchidism

Verloove Vanhorick-Brubakk syndrome is a multiple congenital anomalies/dysmorphic syndrome characterized by multiple skeletal malformations (short femora and humeri, bilateral absence of metatarsal and metacarpal bone in hands and feet, bilateral partial syndactyly of fingers and toes or oligopolysyndactyly, deformed lumbosacral spine), congenital heart disease (truncus arteriosus), lung and urogenital malformations (bilateral bilobar lungs, horseshoe kidney, cryptorchidism), and facial malformations (bilateral cleft lip and palate, micrognathia, small, low-set ears without external meatus). It is lethal in the neonatal period. There have been no further descriptions in the literature since 1981.

3811
(6.1%)

Diethylstilbestrol syndrome

Hypoplasia of the uterus

A malformation syndrome reported in offspring (children and grandchildren) of women exposed to diethylstilbestrol (DES) during pregnancy and is characterized by reproductive tract malformations, decreased fertility and increased risk of developing clear cell carcinoma of the vagina and cervix in young women. Reproductive malformations reported in DES syndrome include small, T-shaped uteri and other uterotubal anomalies that increase the risk of miscarriages in women and epididymal cysts, microphallus, cryptorchidism, or testicular hypoplasia in men. DES, a synthetic nonsteroidal estrogen was widely prescribed from 1940-1970 to prevent miscarriage.

3811
(6.1%)

ATP13A2-related juvenile neuronal ceroid lipofuscinosis

Depressivity

3811
(6.1%)

IMAGe syndrome

Cryptorchidism

Autosomal dominant inheritance Autosomal recessive inheritance

IMAGe syndrome is characterized by the association of Intrauterine growth retardation, Metaphyseal dysplasia (and short limbs), Adrenal hypoplasia congenita, and Genital anomalies. It has been described in less than 20 cases. The patients also present with dysmorphic features (frontal bossing, broad nasal bridge, low-set ears). In boys, genital anomalies include bilateral cryptorchidism, hypospadias, micropenis, and hypogonadotropic hypogonadism. This syndrome is likely to be transmitted as an autosomal recessive trait.