The physiopathology of migraine: the contribution of genetics.
Recent advances in the studies of the genetic liability to migraine include the discovery of two genes responsible for familial hemiplegic migraine (FHM) and the analysis of several sites of linkage or genetic association for the so-called typical migraines, e. g., migraine with (MA) and without aura (MO). The 2 genes implicated in the genetics of FHM are CACNA1A for FHM1 and ATP1A2 for FHM2. It is still unclear how dysfunction in these genes may trigger attacks of migraine with hemiplegic features and, in at least part of the families with FHM, also paroxysmal or progressive ataxia and epileptic seizures. It appears that mutations in CACNA1A responsible for FHM1 alter calcium influx and calcium currents in neurons, possible factors of spreading depression like events. On the other hand, abnormal regulation of intracellular calcium concentrations could alter neurotransmitter release and other cellular functions. In the case of ATP1A2 mutations, haplo-insufficiency of the gene has been hypothesised to result in abnormal potassium level regulation because of faulty Na/K exchange with subsequent depolarisation and increased liability to spreading depression, or/and in abnormal calcium levels because of the concomitant activation of the Na/Ca exchanger, with a mechanism therefore comparable to that at work in FHM1. Much more work is clearly necessary to elucidate these pathophysiological mechanisms; advances in genetics however may represent important steps in the clarification of the physiopathology of the migraine attack.
Montagna
P
P
Department of Neurological Sciences, University of Bologna Medical School, Via U. Foscolo 7, I-40123 Bologna, Italy. pmontagn@neuro.unibo.it
D006801:Humans; D008881:Migraine Disorders / Q000235:genetics* / Q000503:physiopathology*; D020325:Migraine with Aura / Q000235:genetics / Q000503:physiopathology; D020326:Migraine without Aura / Q000235:genetics / Q000503:physiopathology