Spinocerebellar Ataxia Type 8


SCA8 was originally described in association with a single large kindred of individuals suffering from adult-onset SCA having a dominant inheritance pattern with incomplete penetrance. In the original study there was clear distinction between normal and pathological alleles in a single family. Subsequent studies have reinforced the concept that some expanded alleles may not be pathogenic, and that the diagnosis of SCA should be confined to a narrower range of pathological alleles (see Table 3). Patients with pathological alleles have a characteristic presentation. Symptoms first appear between ages 18 and 65, with a mean of 39 years. Initial symptoms consist of gait ataxia, dysarthria, and dysphagia. Findings on examination include spastic and ataxic dysarthria, gaze-evoked nystagmus, limb and gait ataxia, limb spasticity, and diminished vibratory sensation. Progression is generally fairly slow, but severely affected family members become confined to wheelchair by the fourth to fifth decades. SCA8 is associated with an expansion of a polymorphic CTA/CTG repeat in the 3-prime untranslated region of a gene located at 13q21. The length of the repeat present in the general population is 16 to 37 repeats in 99% of alleles. The repeat length that is likely to result in disease ranges from 107 to 127 CTG repeats. The diagnosis of SCA8 is suggested by the demonstration of expansion in one CTG repeat alleles in the SCA8 locus greater than 106 repeats and less than approximately 300 repeats in an ataxia patient.