Synonyms:
Spinocerebellar ataxias (SCAs) a.k.a. spinocerebellar degeneration, formerly olivopontocerebellar ataxia (OPCA)
Spinocerebellar ataxias (SCAs) in General:
This is a group of disorders characterized by ataxia and other findings such as hypotonia. The various subtypes are outlined below
Clinical features:
- Hypotonia and ataxia
MRI:
- Atrophy of Cerebellum & pons
SCA1:
Diagnosis:
Autosomal dominant
CAG repeat, ataxin-1 gene on Chr. 6p23
SCA2 a.k.a. olivopontocereberllar atrophy of Menzel.
Diagnosis:
Autosomal dominant
CAG repeat on chr. 12q24 (normal repeat number is 14-31). Protein= ataxin-2
Pathology:
SCA2: gross; severe atrophy of basis pontis, cerebellum & cervical spinal cord.
Microscopically: Neuronal loss in pons, inferior olivary nucleus, cerebellar cortex & substatia nigra.
Immunohistochemistry: IC2 (binds polyglutamine repeats) positive intranuclear inclusions.
SCA3 a.k.a. Machado-Joseph disease MJD:
Diagnosis:
Autosomal dominant
CAG repeat on chr. 14q32 (normal repeat number is 12-40). Protein= ataxin-3,
Pathology:
SCA3: gross; mild atrophy of the spinal cord & posterior fossa structures.
Microscopically: Neuronal loss in cerebellar dentate nucleus with grumose degeneration (eosinophilic granular material near the bodies of dentate neurons, it consists of preterminal axons). Also neuronal loss in basis pontis, Clarke’s column, LMNs and substatia nigra.
Immunohistochemsitry: Ubiquitin positive intranuclear inclusions, ataxin-3 positive intranuclear inclusions.
SCA4:
Diagnosis:
Autosomal dominant
Chr. 16q22
SCA5:
Diagnosis:
Autosomal dominant
Chr. 11p
SCA6:
Diagnosis:
Autosomal dominant
CAG repeat in human alpha-1a calcium channel subunit gene chr. 19p13. a type of channelopathy. Commoner in Japan. Clinical features: Progressive ataxia (10-30 yrs), all extremities, dysarthria, nystagmus, impaired vibration & position sense. No pyramidal signs
SCA7:
Diagnosis:
Autosomal dominant
CAG repeat, ataxin-7 gene Chr. 3p
SCA8:
Diagnosis:
Autosomal dominant
CTG repeat Chr. 13q21,
SCA9:
Diagnosis:
Autosomal dominant
SCA10:
Diagnosis:
Autosomal dominant
Chr. 22q13,
SCA11:
Diagnosis:
Autosomal dominant
Chr. 15q15,
TTBK2 gene, Protein= tau tubulin kinase-2
SCA12:
Diagnosis:
Autosomal dominant
CAG repeat Chr. 5q31-33
SCA13:
Diagnosis:
Autosomal dominant
Chr. 19q
SCA14:
Diagnosis:
Autosomal dominant
Chr. 19q
SCA15:
Diagnosis:
Autosomal dominant. chr. 3p, ITPR1 gene, protein= type 1 inositol 1,4,5-triphosphate receptor.
SCA16:
Diagnosis:
Autosomal dominant
Chr. 8q
SCA17:
Diagnosis:
Autosomal dominant
Chr. 6q27, CAG repeat >44, TATA-binding protein gene
SCA18:
Diagnosis:
Autosomal dominant
Chr. 7q22-q32
SCA19:
Diagnosis:
Autosomal dominant
Chr.1p21-q21
SCA20:
Diagnosis:
Autosomal dominant
SCA21:
Diagnosis:
Autosomal dominant
Chr.7p21.3-p15.1
SCA22:
Diagnosis:
Autosomal dominant
Chr.1p21-q23
Findings on investigations SCA22:
- Electroretinography ERG: Retinal degeneration in SCA1 & 7