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Clinical revaluation and genetic analysis of six Indian pedigrees, segregating autosomal dominant cerebellar ataxia, slow saccades and peripheral neuropathy, has been undertaken, and expansion at the spinocerebellar ataxia 2 (SCA2) locus was confirmed in 14 affected family members. These families became available from 31 phenotypically similar families seen over the years. In common with other neurodegenerative disorders resulting from expansion of a CAG trinucleotide repeat motif, an inverse correlation between repeat size and age at onset and severity is observed, although the size range (36-45 repeat units) for the expanded alleles is comparatively limited. Saccadic velocity was reduced in all our patients, even in the early stages of the disease. The observation of slow saccades in affected individuals has been proposed previously as an important diagnostic criterion serving to distinguish the SCA2 phenotype. This is now confirmed in a retrospective study of the clinical literature, facilitated by the cloning of the SCA2 gene and the subsequent genetic analysis of families segregating this phenotype. We therefore argue that the clinical appraisal of 'ophthalmoplegia' be subject to more precise definition, as differentiation between the various types of ocular dysfunction can be an important adjunct to diagnosis.

Episodic ataxia type 2 (EA2) is caused by calcium channel (CACNA1A) mutations and typically begins before age 20 years. The molecular basis of late-onset EA2 is unclear. The authors describe a case of late-onset EA2 associated with the first multiple-base pair insertion in CACNA1A. Molecular expression revealed evidence of impaired calcium channel function, suggesting that genetically induced reduction in calcium channel function may associate with cases of late-onset EA2.

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