Autosomal dominant spinocerebellar degenerations. Clinical, pathological, and genetic correlations

Historical review on hereditary spinocerebellar degenerations (SCD) reveale d that some CAG repeat diseases were formerly diagnosed under several diffe rent names because of their clinical and pathological heterogeneity. A gene tic abnormality in these hereditary SCDs (often with expanded CAG repeat) c orresponds to a definite prototypic combination of the principal lesions in the cerebellar, extrapyramidal, and oculomotor systems, which allows neuro pathological differentiation between these entities. Variability of both cl inical and pathological features is mainly related to the patient's age at onset, which is often correlated with the number of CAG repeat size. Severa l characteristics are suggestive of these SCD: preferential degeneration of specific systems, size reduction at cellular or tissue level not accompani ed by glial reaction (simple atrophy or hypoplastic change) and presence of recently indentified ubiquitin positive inclusions in neurons are characte ristic of these SCDs. These features provide further insight into the pheno typic development of a genetic abnormality.