Résumé
Three neurological conditions, familial hemiplegic migraine (FHM), episodic ataxia type 2 (EA2), and spino-cerebellar ataxia type 6 (SCA6) are caused by mutations in the neuronal P/Q type calcium channel alpha 1A subunit gene (CACNA1A) on chromosome 19p13. These clinically distinct conditions are associated with distinct types of mutations, missense mutation in FMH, truncating in EA2, and expansion of a CAG triplet in SCA6. The chapter describes the clinical features, genetics, and pathogenesis of CACNA1A mutation related conditions of FHM, EA2, and SCA6. Familial hemiplegic migraine (FHM) is a hereditary form of migraine with aura characterized by the presence of motor weakness during the aura. FHM is the only migraine subtype for which a monogenic and autosomal dominant mode of inheritance has been established. Typical attacks include a unilateral motor deficit associated with paresthesias, speech disturbances, or visual signs. EA2 is also an autosomal dominant disorder. It is characterized by recurrent attacks of generalized ataxia, usually starting during childhood or adolescence. Unsteadiness, limb incoordination, dysarthria, and generalized myokimia are present during attacks. Autosomal dominant SCA6 is a late onset progressive neurological condition. In SCA6, ataxia is associated to ophthalmoplegia, pyramidal and extrapyramidal signs, dysarthria, amyotrophy, and pigmentary retinopathy.