[A clinical study of a family affected with HLA-linked hereditary spinocerebellar ataxia]

The gene locus of hereditary olivopontocerebellar atrophy (OPCA) has been mapped to the short arm of chromosome 6. This locus has been termed as SCA 1 and it is linked to HLA locus. Linkage for OPCA locus to HLA was first been reported by Yakura et al. We had a chance to re-investigate the original family reported by them. Among the members affected, 6 cases were autopsied and their clinical and pathological features were reported by Fujimoto et al. Kudoh et al, and Ikeda. We clinically studied 2 additional patients in this pedigree. The clinical features of these patients, including 6 previously reported cases, were characterized by 1) cerebellar ataxia predominating throughout clinical course; 2) pyramidal tract involvement, characterized by pathological reflexes, with hyper-reflexia or terminal hyporeflexia; 3) generalized muscle atrophy; 4) slow eye movement; 5) facial and tongue atrophy; 6) optic disc pallor; 7) terminal external ophthalmoparesis; 8) mydriasis and sluggish light reflex; 9) mild peripheral neuropathy; 10) mild reduction of deep sense; 11) bulbar symptom; 12) emotional lability, irritation, or euphoria dominating terminally. Clinically, there are certain similarities between this pedigree and other reported pedigrees of which linkage for OPCA locus to HLA have been proved. Furthermore, clinico-pathological reports of hereditary OPCA showing slow eye movement share numbers of clinical characteristics observed in the patients of this pedigree. Accumulating linkage data suggest that hereditary OPCA might be heterogenous disorder genetically. Whether there are any correlation between linkage data and clinico-pathological findings is essential to establish disease entities, and to re-classify hereditary OPCA and its related disorders.