Spinocerebellar ataxias caused by polyglutamine expansions.

Abstract

Autosomal dominant cerebellar ataxias (ADCA) constitute a group of disorders, clinically and molecularly heterogeneous. They are characterized by variable degrees of cerebellar and brainstem degeneration or dysfunction. Neuronal loss variably affects the pons, the inferior olive, the basal ganglia, the cerebellum and its afferent and efferent fibers. Onset is generally during the third or fourth decade but can also occur in childhood or in the old age. Patients usually present with progressive cerebellar ataxia and associated neurological signs, such as ophthalmoplegia, pyramidal or extrapyramidal signs, deep sensory loss and dementia. Attempts to classify subtypes of ADCA were largely unsatisfactory until AE Harding distinguished three phenotypes based on clinical associated signs. ADCA type I is the most common subtype and variably combines cerebellar ataxia, dysarthria, ophthalmoplegia, pyramidal and extrapyramidal signs, deep sensory loss, amyotrophy and dementia. However, several other signs and symptoms may also be associated, i.e., slow eye movements, sphincter disturbances, axonal neuropathy, fasciculation and/ or swallowing difficulties. ADCA type II was first described by Froment et al and is characterized by the association of progressive macular degeneration with cerebellar ataxia. Finally, ADCA type III denotes a “pure”, generally late onset, cerebellar syndrome.