Ataxia, and Glaucoma

Early-onset X-linked optic atrophy is a rare form of hereditary optic atrophy, seen in only 4 families to date, with an onset in early childhood, characterized by progressive loss of visual acuity, significant optic nerve pallor and occasionally additional neurological manifestations, with females being unaffected.

EARLY-ONSET X-LINKED OPTIC ATROPHY Is also known as optic atrophy, non-leber type, with early onset|optic atrophy type 2|opa2|non-leber type optic atrophy with early-onset|optic atrophy, x-linked

• Intellectual disability
• Peripheral neuropathy
• Dysarthria
• Optic atrophy
• Tremor

SOURCES: ORPHANET MESH OMIM MENDELIAN

PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL DOMINANT 5; PEOA5 Is also known as progressive external ophthalmoplegia, autosomal dominant 5

• Hearing impairment
• Ataxia
• Ptosis
• Dysarthria
• Fatigue

SOURCES: MESH 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

Charcot-Marie-Tooth disease type 4B3 (CMT4B3) is a subtype of Charcot-Marie-Tooth type 4 characterized by a childhood onset of slowly progressing, demyelinating sensorimotor neuropathy, focally folded myelin sheaths in nerve biopsy, reduced nerve conduction velocities (less than 38 m/s), and the typical CMT phenotype (i.e. distal muscle weakness and atrophy, and sensory loss).

CHARCOT-MARIE-TOOTH DISEASE TYPE 4B3 Is also known as charcot-marie-tooth disease with focally folded myelin|cmt4b3

• Intellectual disability
• Microcephaly
• Scoliosis
• Ataxia
• Strabismus

SOURCES: OMIM ORPHANET MENDELIAN

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.

AUTOSOMAL RECESSIVE SPASTIC PARAPLEGIA TYPE 75 Is also known as spg75

• Intellectual disability
• Global developmental delay
• Generalized hypotonia
• Nystagmus
• Spasticity

SOURCES: OMIM ORPHANET MENDELIAN

Wolfram-like syndrome is a rare endocrine disease characterized by the triad of adult-onset diabetes mellitus, progressive hearing loss (usually presenting in the first decade of life and principally of low to moderate frequencies), and/or juvenile-onset optic atrophy. Psychiatric (i.e. anxiety, depression, hallucinations) and sleep disorders, the only neurologic abnormalities observed in this disease, have been reported in rare cases. Unlike Wolfram syndrome, patients with Wolfram-like syndrome do not report endocrine or cardiac findings.

WOLFRAM-LIKE SYNDROME Is also known as hearing loss, progressive, with optic atrophy and/or impaired glucose regulation

• Hearing impairment
• Ataxia
• Sensorineural hearing impairment
• Visual impairment
• Peripheral neuropathy

SOURCES: MESH OMIM ORPHANET MENDELIAN

Von Hippel-Lindau disease (VHL) is a familial cancer predisposition syndrome associated with a variety of malignant and benign neoplasms, most frequently retinal, cerebellar, and spinal hemangioblastoma, renal cell carcinoma (RCC), and pheochromocytoma.

VON HIPPEL-LINDAU DISEASE Is also known as familial cerebelloretinal angiomatosis|von hippel-lindau syndrome|lindau disease|vhl

• Hearing impairment
• Ataxia
• Nystagmus
• Neoplasm
• Sensorineural hearing impairment

SOURCES: ORPHANET MENDELIAN

Wolfram syndrome (WS) also known as DIDMOAD, is a neurodegenerative disorder characterized by type I diabetes mellitus (DM), diabetes insipidus (DI), sensorineural deafness (D), bilateral optical atrophy (OA) and neurological signs. Other related problems are urinary tract atony, ataxia, peripheral neuropathy, psychiatric disorders and/or seizures. 2 types of WS may be distinguished: type 1 and type 2 (WS1 and WS2).

WOLFRAM SYNDROME Is also known as didmoad syndrome|diabetes insipidus-diabetes mellitus-optic atrophy-deafness syndrome

• Intellectual disability
• Seizures
• Ataxia
• Nystagmus
• Sensorineural hearing impairment

SOURCES: ORPHANET OMIM MENDELIAN

Autosomal recessive cerebellar ataxia due to STUB1 deficiency is a rare hereditary ataxia characterized by progressive truncal and limb ataxia resulting in gait instability. Dysarthria, dysphagia, nystagmus, spasticity of the lower limbs, mild peripheral sensory neuropathy, cognitive impairment and accelerated ageing have also been associated.

AUTOSOMAL RECESSIVE CEREBELLAR ATAXIA DUE TO STUB1 DEFICIENCY Is also known as scar16|spinocerebellar ataxia autosomal recessive type 16

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

SOURCES: ORPHANET OMIM MENDELIAN

Knobloch syndrome (KS) is defined by vitreoretinal and macular degeneration, and occipital encephalocele.

KNOBLOCH SYNDROME Is also known as retinal detachment and occipital encephalocele|knobloch-layer syndrome|retinal detachment-occipital encephalocele syndrome|kno

• Seizures
• Global developmental delay
• Generalized hypotonia
• Ataxia
• Nystagmus

SOURCES: OMIM MESH ORPHANET MENDELIAN