Familial Episodic Ataxia

Abstract

Familial episodic ataxias are inherited channelopathies that manifest as episodes of vertigo and ataxia triggered by emotional stress and physical exertion. Mutations in two neuronal ion-channel genes KCNA1 and CACNA1A abundantly expressed in the cerebellum account for the majority of the identified cases of episodic ataxia. Overlapping features between episodic ataxia and the more common recurrent vertigo and ataxia syndromes, particularly those associated with migraine, suggest shared underlying mechanisms. Altered neuronal excitability in the brain and inner ear could contribute to the central and peripheral features of migrainous vertigo. Given the familial aggregation of migraine and migrainous vertigo, our objective was to identify predisposing genetic factors. Preliminary findings demonstrate that migrainous vertigo is genetically heterogeneous and complex. Efforts are ongoing to perform genomewide association studies to identify risk alleles for migrainous vertigo, which may also be relevant to migraine in general.