AUTOSOMAL-DOMINANT CEREBELLAR-ATAXIA WITH PIGMENTARY MACULAR DYSTROPHY - A CLINICAL AND GENETIC-STUDY OF 8 FAMILIES

We describe 54 members of eight families with a distinct autosomal dom inant cerebellar ataxia associated with visual failure secondary to a pigmentary macular dystrophy. The presenting symptom was ataxia in two -thirds of patients and visual failure or both in the remainder. The m acular abnormalities were often subtle in early cases, even in some wi th moderately reduced visual acuity. Other neurological features Inclu ded pyramidal tract signs and a supranuclear ophthalmoplegia with prog ressive saccadic palsy. Ages of onset and clinical course were very va riable, even within families, and included a rapidly progressive, infa ntile-onset phenotype. Pedigree analysis showed the existence of non-m anifesting obligate carriers and anticipation in the offspring of affe cted fathers; transmission of the disease to severe, infantile-onset c ases was always from an affected father. Similar genetic phenomena hav e been reported in myotonic dystrophy and Huntington's disease and it is likely that the gene mutation in this condition will similarly cons ist of an unstable trinucleotide repeat expansion.