The genetic features of 24 patients affected by familial and sporadic hemiplegic migraine

Familial hemiplegic migraine (FHM) is the only migraine subtype for which a monogenic mode of inheritance, autosomal dominant has been clearly established. It is genetically heterogeneous and at least three different genes exist (CACNA1A, ATP1A2, and SCN1A), the so-called FHM1, FHM2, and FHM3 genes, respectively. Sporadic hemiplegic migraine (SHM) is a disorder, in which some patients may have their pathophysiology identical to FHM, but others, possibly the majority, may have different pathophysiology, probably related to the mechanisms of typical migraine with aura. In our study, we have screened the DNA of 24 patients affected by FHM and SHM. Only in three patients, 2 sporadic and 1 familial cases, we have described genetic mutations, all of them in the ATP1A2 gene. In our opinion, these results demonstrate a more frequent involvement of the ATP1A2 gene not only in the sporadic form, but probably also in the Italian FHM patients without permanent cerebellar signs. Moreover, the absence of CACNA1A, ATP1A2 and SCN1A mutations in the other 12 familial cases suggests the involvement of still unknown genes.