MOLECULAR GENETICS OF THE HEREDITARY ATAXIAS

Publisher Summary The hereditary ataxias are a heterogeneous group of inherited neurodegenerative diseases whose clinical presentation is characterized by loss of coordination of movements as a main feature. The chapter discusses the Harding's classification, utilized as reference framework. Harding used the acronym autosomal dominant cerebellar ataxia (ADCA) to label the disorders and distinguished several types according to clinical features that are consistently observed within families. The chapter focuses on some diseases that changed status from ataxia of unknown cause to diseases whose genetic defect has been identified. These include several dominantly inherited, progressive, usually late-onset ataxias and Friedreich ataxia, generally an early-onset disorder. Friedreich ataxia (FRDA) is the most common of the hereditary ataxias that seems to have a fairly similar prevalence of around 2 ×10 −5 in almost all studied populations, with local clusters due to a founder effect. The neuropathological features of FRDA are specific for the disorder and differ from those found in other hereditary ataxias.