Ion Channel Genes and Ataxia

Abstract

In this review we will discuss ataxic disorders attributed to mutations in ion channel genes. Such disorders seem to preferentially effect cerebellar Purkinje cell function, but not exclusively so. Some mutations result in gating alterations, such as loss-of-function or gain-of-function of the channels and others have no effect on channel function and may lead simply to poor trafficking or genetic deletion of the channel. Phenotypic presentation is varied and mutations in ion channel genes lead to congenital, static or progressive cerebellar ataxia and other features, including extrapyramidal symptoms, pyramidal symptoms, neuropsychological disturbance, autonomic dysfunction, and seizures among many others. Unique mutations of the same gene can also lead to completely different manifestations and phenotypes. While better characterization of some of these disorders may ultimately allow us to tailor individual therapy toward the particular type of ion channel dysfunction, the task of restoring channel expression will require more substantial advances. Here we endeavor to summarize the various types of ataxia related to ion channel gene mutations, their clinical features, and current data or theories on etiology of dysfunction.