SPINOCEREBELLAR ATAXIA TYPE-6 - FREQUENCY OF THE MUTATION AND GENOTYPE-PHENOTYPE CORRELATIONS

Spinocerebellar ataxia type 6 (SCAG) is the most recently identified m utation causing autosomal-dominant cerebellar ataxia without retinal d egeneration (ADCA). The SCAG mutation is allelic with episodic ataxia type 2 (EA-2), but the two differ clinically because of the presence o f progressive, rather than episodic, ataxia in SCA6. SCAG accounts for 12% of families with ADCA in an ethnically heterogeneous population o f patients. Clinical examination, quantitative eye movement testing, a nd imaging data show that the brainstem is normal in most patients wit h SCAG, especially within the first 10 years of symptoms. Most patient s show progressive ataxia from the onset, but several patients show an episodic course resembling EA-2. Thus, SCA6 mutations not only accoun t for patients with ADCA I and ADCA III phenotypes but also for some p atients presenting with episodic features that are typical for EA-2. I nterestingly, a compound heterozygote for the SCAG expansion manifeste d an earlier onset and more rapid course than family members with the same larger expanded allele.