Spinocerebellar Ataxias

Diseases classified as spinocerebellar ataxias typically feature ataxia as a prominent feature, but many also are associated with various other neurological deficits. The term spinocerebellar ataxia usually implies inheritance with an autosomal dominant pattern, but sporadic forms exist. Because of significant clinical and pathological variability, even within single entities, spinocerebellar ataxias have been difficult to characterize and diagnose. Recent advances in genetic characterization have provided insight into better classification and understanding of the pathogenetic mechanisms of these diseases. A number of the spinocerebellar ataxias have been shown to have trinucleotide repeat expansions which can result in the expression of elongated polyglutamine residues in the protein encoded by the affected gene. In other spinocerebellar ataxias, nucleotide repeat expansions occur in non-translated regions of the gene and may alter gene expression in other ways. In yet other spinocerebellar ataxias structural proteins or functional proteins are mutated, but many of the spinocerebellar ataxias remain uncharacterized genetically.