AUTOSOMAL-DOMINANT CEREBELLAR-ATAXIA TYPE-I - CLINICAL-FEATURES AND MRT IN FAMILIES WITH SCA1, SCA2 AND SCA3

Sixty-five patients suffering from autosomal dominant cerebellar ataxi a-I(ADCA-1) were subjected to a genotype phenotype correlation analysi s using molecular genetic assignment to the spinocerebellar ataxia typ e 1, 2 or 3 (SCAI, -2 or -3) locus, clinical examination, eye movement recording and morphometric analysis of MRIs. Pyramidal tract signs, p ale discs and dysphagia were more frequent in SCAI compared with SCA2 and SCA3 patients. Saccade velocity was reduced in 56% of SCA1 and all SCA2, but only in 30% of SCA3 patients. MRIs of SCA2 patients showed atrophy changes typical of severe olivopontocerebellar atrophy (OPCA). The morphological changes in SCAI were similar but less pronounced. I n contrast, SCA3 patients had only mild cerebellar and brain stem atro phy distinct from typical OPCA. The principal finding of this study is that mutations of the SCA2 and SCA3 gene cause phenotypes which can b e distinguished in vivo by recording of eye movements and morphometric MRI analysis. Correlative plotting of saccade velocity and diameter o f the middle cerebellar peduncle yields a clear separation of SCA2 and SCA3. Spinocerebellar ataxia type 1 falls into an intermediate range that overlaps with both SCA2 and SCA3. However the clinical syndrome o bserved in SCA1 patients is different from that in SCA2 and SCA3.