Dh. Geschwind et al., SPINOCEREBELLAR ATAXIA TYPE-6 - FREQUENCY OF THE MUTATION AND GENOTYPE-PHENOTYPE CORRELATIONS, Neurology, 49(5), 1997, pp. 1247-1251
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.