Spinocerebellar Ataxia 1 (SCA1)
Inheritance
Autosomal dominant
SCA 1 shows anticipation, mainly through paternal inheritance.
Molecular genetics and pathogenesis
SCA 1 is due to an expanded CAG repeat in a coding region of the SCA1 gene, encoding ataxin-1, a protein of unknown function. Like the other dominant polyglutamine diseases, the toxic effect is believed to be primarily due to a gain of function of the mutated protein, rather than a lost function of the wild-type.
Clinical manifestations
Ataxia of limbs, gait, speech, eye movements; exaggerated reflexes, extrapyramidal signs, especially parkinsonism and dystonia; spasticity; mild cognitive impairment; peripheral neuropathy. Symptoms usually begin around age 30.
Treatment
Very few clinical trials have been conducted in spinocerebellar ataxia, and no randomized trials have shown benefit for any agent. A recent double-blind trial of buspirone did not show any benefit.
References
Assadi M, Campellone JV, Janson CG, Veloski JJ, Schwartzman RJ, Leone P. Treatment of spinocerebellar ataxia with buspirone. J Neurol Sci. 2007 Sep 15;260(1-2):143-6.
PMID: 17512011
OMIM
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164400
