Generalized hypotonia, and Bilateral sensorineural hearing impairment

Spinocerebellar ataxia type 31 (SCA31) is a very rare subtype of autosomal dominant cerebellar ataxia type III (ADCA type III; see this term) characterized by the late-onset of cerebral ataxia, dysarthria and horizontal gaze nystagmus, and that is occasionally accompanied by pyramidal signs, tremor, decreased vibration sense and hearing difficulties.

SPINOCEREBELLAR ATAXIA TYPE 31 Is also known as sca31|spinocerebellar ataxia, 16q22-linked

• Generalized hypotonia
• Hearing impairment
• Ataxia
• Nystagmus
• Sensorineural hearing impairment

SOURCES: MESH OMIM ORPHANET MENDELIAN

Spinal muscular atrophy-progressive myoclonic epilepsy syndrome is characterized by hereditary myoclonus and progressive distal muscular atrophy. Less than 10 cases have been reported. Treatment with clonazepam results in complete and lasting improvement of the myoclonus.

SPINAL MUSCULAR ATROPHY-PROGRESSIVE MYOCLONIC EPILEPSY SYNDROME Is also known as hereditary myoclonus-progressive distal muscular atrophy syndrome|jankovic-rivera syndrome|myoclonus, hereditary, with progressive distal muscular atrophy

• Seizures
• Generalized hypotonia
• Hearing impairment
• Scoliosis
• Sensorineural hearing impairment

SOURCES: ORPHANET MESH OMIM MENDELIAN

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.

X-LINKED CHARCOT-MARIE-TOOTH DISEASE TYPE 5 Is also known as cmt5x|cmtx5|optic atrophy, polyneuropathy, and deafness|rosenberg-chutorian syndrome|charcot-marie-tooth neuropathy, x-linked recessive, 5

• Global developmental delay
• Generalized hypotonia
• Hearing impairment
• Scoliosis
• Ataxia

SOURCES: OMIM ORPHANET MENDELIAN

'Behr syndrome' is a clinical term that refers to the constellation of early-onset optic atrophy accompanied by neurologic features, including ataxia, pyramidal signs, spasticity, and mental retardation (Behr, 1909; Thomas et al., 1984).Patients with mutations in genes other than OPA1 can present with clinical features reminiscent of Behr syndrome. Mutations in one of these genes, OPA3 (OMIM ), result in type III 3-methylglutaconic aciduria (MGCA3 ). Lerman-Sagie (1995) noted that the abnormal urinary pattern in MGCA3 may not be picked up by routine organic acid analysis, suggesting that early reports of Behr syndrome with normal metabolic features may actually have been 3-methylglutaconic aciduria type III.

BEHR SYNDROME; BEHRS Is also known as optic atrophy, infantile hereditary, with neurologic abnormalities

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Hearing impairment

SOURCES: ORPHANET OMIM MESH MENDELIAN

METACHROMATIC LEUKODYSTROPHY, JUVENILE FORM Is also known as arylsulfatase a deficiency, juvenile form|mld, juvenile form

• Seizures
• Generalized hypotonia
• Muscle weakness
• Spasticity
• Dysarthria

SOURCES: ORPHANET MENDELIAN

Waardenburg syndrome type 2 is an auditory-pigmentary syndrome characterized by pigmentary abnormalities of the hair, skin, and eyes; congenital sensorineural hearing loss; and the absence of 'dystopia canthorum,' the lateral displacement of the inner canthus of each eye, which is seen in some other forms of WS (review by Read and Newton, 1997). Individuals with WS type 2E, which is caused by mutation in the SOX10 gene (OMIM ), may have neurologic abnormalities, including mental impairment, myelination defects, and ataxia. Waardenburg syndrome type 2 is genetically heterogeneous (see WS2A; {193510}).For a description of other clinical variants of Waardenburg syndrome, see WS1 (OMIM ), WS3 (OMIM ), and WS4 (OMIM ).

WAARDENBURG SYNDROME, TYPE 2E; WS2E Is also known as hypogonadotropic hypogonadism with anosmia and deafness, with or without hypopigmentation|waardenburg syndrome, type 2e, with or without neurologic involvement|ws2e, with or without neurologic involvement|waardenburg syndrome, type iie

• Intellectual disability
• Global developmental delay
• Generalized hypotonia
• Hearing impairment
• Ataxia

SOURCES: OMIM MENDELIAN

Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A) is an autosomal recessive disorder with congenital muscular dystrophy resulting in muscle weakness early in life and brain and eye anomalies. It is usually associated with delayed psychomotor development and shortened life expectancy. The phenotype includes the alternative clinical designations Walker-Warburg syndrome (WWS) and muscle-eye-brain disease (MEB). The disorder represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1 ), collectively known as dystroglycanopathies (summary by Stevens et al., 2013).For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (OMIM ).

MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 12; MDDGA12 Is also known as walker-warburg syndrome or muscle-eye-brain disease, pomk-related

• Seizures
• Global developmental delay
• Generalized hypotonia
• Hearing impairment
• Microcephaly

SOURCES: OMIM MENDELIAN

FG syndrome-4 is an X-linked recessive mental retardation syndrome characterized by congenital hypotonia, constipation, behavioral disturbances, and dysmorphic features (summary by Piluso et al., 2003).The name 'FG' derives from the first description of the disorder (FGS1 ) by Opitz and Kaveggia (1974), who named it 'FG syndrome' according to the Opitz system of using initials of patients' surnames. For a phenotypic description and a discussion of genetic heterogeneity of FG syndrome, see FGS1 (OMIM ).FGS4 is typically associated with missense or hypomorphic mutations in the CASK gene. See also the more severe disorder MICPCH (OMIM ), an allelic disorder caused by complete loss-of-function mutations in the CASK gene (Tarpey et al., 2009).

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: OMIM MENDELIAN

A condition with multiple abnormalities including mild to severe intellectual disability, impaired growth from birth leading to short stature, and microcephaly. Affected individuals may also have distinctive facial features (including a small forehead, a short nose, a small lower jaw, a flat area between the nose and mouth (philtrum), and prominent cheeks), sensorineural hearing loss, and heart malformations

WARSAW BREAKAGE SYNDROME Is also known as wabs

• Intellectual disability
• Global developmental delay
• Generalized hypotonia
• Hearing impairment
• Microcephaly

SOURCES: ORPHANET OMIM MENDELIAN

Brown-Vialetto-Van Laere syndrome-2 is an autosomal recessive progressive neurologic disorder characterized by early childhood onset of sensorineural deafness, bulbar dysfunction, and severe diffuse muscle weakness and wasting of the upper and lower limbs and axial muscles, resulting in respiratory insufficiency. Some patients may lose independent ambulation. Because it results from a defect in riboflavin metabolism, some patients may benefit from high-dose riboflavin supplementation (summary by Johnson et al., 2012; Foley et al., 2014).For discussion of genetic heterogeneity of Brown-Vialetto-Van Laere syndrome, see BVVLS1 (OMIM ).

• Generalized hypotonia
• Hearing impairment
• Scoliosis
• Ataxia
• Nystagmus

SOURCES: OMIM MENDELIAN