Machado–Joseph Disease

Machado–Joseph disease is an autosomal dominant neurodegenerative disorder caused by CAG repeat expansions in the ATXN3 gene. Clinical features include progressive cerebellar ataxia, pyramidal and extrapyramidal signs, peripheral neuropathy, and ophthalmoplegia. Pathophysiology involves polyglutamine-mediated neuronal toxicity affecting the cerebellum, brainstem, and basal ganglia. Diagnosis is genetic, supported by clinical and neuroimaging findings. Management is supportive, including physical therapy and symptomatic pharmacologic treatment; prognosis involves progressive motor disability.