Clusters of non-truncating mutations of P/Q type Ca2+ channel subunit Ca(v)2.1 causing episodic ataxia 2

Episodic ataxia type 2 (EA2, MIM 108500) is one of three allelic disorders due to mutations of the CACNA1A gene coding for the Cav2.1 subunit of P/Q type voltage gated Ca2+ channels. The other two allelic diseases are familial hemiplegic migraine (FHM, MIM 141500) and spinocerebellar ataxia type 6 (SCA6, MIM 183086). EA2 is characterised by a complex and highly variable phenotype, widely overlapping that of SCA6.1,2 Its main features are episodes of vertigo or ataxia of variable duration and frequency, a permanent cerebellar deficit of variable severity, sometimes progressive, and a cerebellar atrophy typically starting from the anterior portion of vermis. Recently dyskynesia,3 muscular weakness,4 and epilepsy5 have been described in association with EA2. FHM, on the other hand, is characterised by migraine attacks preceded by symptoms such as unilateral limb paresis or paralysis, paraesthesias, and dysphasia. Interictal cerebellar signs are . . .