Hearing impairment, and Neurodegeneration

Childhood-onset neurodegeneration with ataxia, dystonia, and gaze palsy is an autosomal recessive progressive disorder characterized by onset of gait ataxia, cognitive decline, and gaze palsy in the first or second decades. Additional features include dysarthria, dystonia, and athetoid movements. Some patients may become wheelchair-bound as young adults (summary by Haack et al., 2016).

• Seizures
• Hearing impairment
• Ataxia
• Nystagmus
• Hyperreflexia

SOURCES: OMIM MENDELIAN

Hereditary sensory neuropathy type IE is an autosomal dominant neurodegenerative disorder characterized by adult onset of progressive peripheral sensory loss associated with progressive hearing impairment and early-onset dementia (summary by Klein et al., 2011).For a discussion of genetic heterogeneity of HSN, see HSAN1A (OMIM ).

HEREDITARY SENSORY NEUROPATHY-DEAFNESS-DEMENTIA SYNDROME Is also known as hsn ie|hsn1e|hereditary sensory neuropathy-sensorineural hearing loss-dementia syndrome|hsan1e|neuropathy, hereditary sensory, with hearing loss and dementia

• Seizures
• Hearing impairment
• Ataxia
• Sensorineural hearing impairment
• Pain

SOURCES: ORPHANET MESH OMIM MENDELIAN

Congenital cataract-hearing loss-severe developmental delay syndrome is a rare, genetic, lethal, neurometabolic disease characterized by congenital cataracts, sensorineural hearing loss, severe psychomotor developmental delay, severe, generalized muscular hypotonia, and central nervous system abnormalities (incl. cerebellar and cerebral hypoplasia, hypomyelination, wide subarachnoid spaces), in the presence of low serum copper and ceruloplasmin. Nystagmus and seizures have also been reported.

CONGENITAL CATARACT-HEARING LOSS-SEVERE DEVELOPMENTAL DELAY SYNDROME Is also known as congenital cataract-deafness-severe developmental delay syndrome|lethal neurodegenerative disorder due to copper transport defect

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

SOURCES: ORPHANET OMIM MENDELIAN

Autosomal dominant optic atrophy is characterized by an insidious onset of visual impairment in early childhood with moderate to severe loss of visual acuity, temporal optic disc pallor, color vision deficits, and centrocecal scotoma of variable density (Votruba et al., 1998).Some patients with mutations in the OPA1 gene may also develop extraocular neurologic features, such as deafness, progressive external ophthalmoplegia, muscle cramps, hyperreflexia, and ataxia; see {125250}. There appears to be a wide range of intermediate phenotypes (Yu-Wai-Man et al., 2010).Yu-Wai-Man et al. (2009) provided a detailed review of autosomal dominant optic atrophy and Leber hereditary optic neuropathy (LHON ), with emphasis on the selective vulnerability of retinal ganglion cells to mitochondrial dysfunction in both disorders. Genetic Heterogeneity of Optic AtrophyOptic atrophy-2 (OPA2 ) maps to chromosome Xp11.4-p11.21. OPA3 (OMIM ) is caused by mutation in the OPA3 gene (OMIM ) on chromosome 19q13. OPA4 (OMIM ) maps to chromosome 18q12.2-q12.3. OPA5 (OMIM ) is caused by mutation in the DNM1L gene (OMIM ) on chromosome 12p11. OPA6 (OMIM ) maps to chromosome 8q21-q22. OPA7 (OMIM ) is caused by mutation in the TMEM126A gene (OMIM ) on chromosome 11q14. OPA8 (OMIM ) maps to chromosome 16q21-q22. OPA9 (OMIM ) is caused by mutation in the ACO2 gene (OMIM ) on chromosome 22q13; OPA10 (OMIM ) is caused by mutation in the RTN4IP1 gene (OMIM ) on chromosome 6q21; and OPA11 (OMIM ) is caused by mutation in the YME1L1 gene (OMIM ) on chromosome 10p12.

OPTIC ATROPHY 1; OPA1 Is also known as kjer-type optic atrophy|optic atrophy, kjer type|oak|optic atrophy, juvenile

• Hearing impairment
• Ataxia
• Strabismus
• Sensorineural hearing impairment
• Visual impairment

SOURCES: ORPHANET OMIM MENDELIAN

Cobblestone lissencephaly without muscular or ocular involvement is a form of cobblestone lissencephaly characterized by a constellation of brain malformations which can either exist alone or in conjunction with minimal muscular and ocular abnormalities. The clinical features of the disease include severe developmental delay, increased head circumference, hydrocephalus and seizures.

COBBLESTONE LISSENCEPHALY WITHOUT MUSCULAR OR OCULAR INVOLVEMENT Is also known as lissencephaly type 2 without muscular or ocular involvement|lissencephaly type 2 without muscular or eye involvement|cobblestone lissencephaly without muscular or eye involvement

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

SOURCES: ORPHANET OMIM MENDELIAN

Stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS) is an autosomal recessive neurodegenerative disorder with onset in the first years of life following normal early development. Patient have cyclic episodic deterioration in response to stress, such as infection or febrile illness. The severity is highly variable: some patients develop seizures early in life that are associated with loss of developmental milestones and early sudden death in childhood, whereas others present at a later age with muscle weakness, gait ataxia, impaired speech, more subtle clinical deterioration, and cognitive decline. Neurologic involvement includes gait ataxia, cerebellar signs associated with cerebellar atrophy, generalized brain atrophy, impaired intellectual development, hearing loss, and peripheral neuropathy (summary by Ghosh et al., 2018).

• Seizures
• Global developmental delay
• Hearing impairment
• Ataxia
• Nystagmus

SOURCES: OMIM MENDELIAN

Mitochondrial short-chain enoyl-CoA hydratase-1 deficiency is an autosomal recessive inborn error of metabolism characterized by severely delayed psychomotor development, neurodegeneration, increased lactic acid, and brain lesions in the basal ganglia (summary by Peters et al., 2014).

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

SOURCES: OMIM MENDELIAN

Spinocerebellar ataxia type 36 (SCA36) is a subtype of autosomal dominant cerebellar ataxia type 1 (ADCA type 1; see this term) characterized by gait and limb ataxia, lower limb spasticity, dysarthria, muscle fasiculations, tongue atrophy and hyperreflexia.

SPINOCEREBELLAR ATAXIA TYPE 36 Is also known as sca36|asidan

• Hearing impairment
• Ataxia
• Nystagmus
• Spasticity
• Ptosis

SOURCES: OMIM ORPHANET MENDELIAN

Developmental malformations-deafness-dystonia syndrome is characterised by the association of midline malformations, sensory hearing loss, and a delayed-onset generalised dystonia syndrome.

• Intellectual disability
• Global developmental delay
• Short stature
• Hearing impairment
• Scoliosis

SOURCES: MESH ORPHANET OMIM MENDELIAN

Mitochondrial complex III deficiency nuclear type 2 is an autosomal recessive severe neurodegenerative disorder that usually presents in childhood, but may show later onset, even in adulthood. Affected individuals have motor disability, with ataxia, apraxia, dystonia, and dysarthria, associated with necrotic lesions throughout the brain. Most patients also have cognitive impairment and axonal neuropathy and become severely disabled later in life (summary by Ghezzi et al., 2011). The disorder may present clinically as spinocerebellar ataxia or Leigh syndrome, or with psychiatric disturbances (Morino et al., 2014; Atwal, 2014; Nogueira et al., 2013).For a discussion of genetic heterogeneity of mitochondrial complex III deficiency, see MC3DN1 (OMIM ).

• Intellectual disability
• Global developmental delay
• Hearing impairment
• Ataxia
• Nystagmus

SOURCES: OMIM MENDELIAN