Genetics of Familial Hemiplegic Migraine: state of the art

At present, very few is known on the genetics of common Migraines, most likely to be considered a multifactorial disease. Recently, the CACNA1A gene encoding the brain-specific P/Q type calcium channel alpha 1 subunit, has been cloned and mutations in this gene, located on chromosome 19p13, have been shown to be involved in familial hemiplegic migraine (FHM), a rare autosomal dominantly inherited subtype of migraine with aura. Being part of the migraine spectrum, FHM represents a good model to study the genetics of more common forms of migraine. Different classes of mutations within the CACNA1A gene have been associated with different diseases, thus identifying a new member among 'channelopathies'. Variable clinical expression and genetic heterogeneity of FHM will be discussed.