Autosomal dominant cerebellar ataxia type I: oculomotor abnormalities in families with SCA1, SCA2, and SCA3

Forty-six patients suffering from autosomal dominant cerebellar ataxia type I (ADCA I) underwent to a genotype-phenotype correlation analysis by molec ular genetic assignment to the spinocerebellar ataxia type 1, 2, or 3 (SCA1 , SCA2, SCA3) genetic locus and electrooculography. Oculomotor deficits tha t are attributed to dysfunction of cerebellar structures occurred in all th ree mutations without major differences between the groups. Gaze-evoked nys tagmus, however, was not found to be associated with SCA2. Square wave jerk s were exclusively observed in SCA3. The gain in vestibule-ocular reflex wa s significantly impaired in SCA3 and SCA1. In SCA3 the severity of vestibul ar impairment increased with CAG repeat length. Severe saccade slowing was a highly characteristic feature of SCA2. In SCA3 saccade velocity was norma l to mildly reduced while SCA1 fell into an intermediate range. The present data show that each mutation is associated with a distinct syndrome of ocu lomotor deficits. Reduced saccade velocity and the absence of both square-w ave jerks and gaze-evoked nystagmus allow one SCA2 to be distinguished from SCA3 patients in almost all cases. The eye movement disorder of SCA1 patie nts, however, overlaps with both SCA2 and SCA3.