Migraines carry a substantial genetic liability, and in families affected with the typical migraines (migraine with, MA, and without aura, MO) linkage to some chromosomal loci has been reported. As yet however, no genes are known for MA/MO, while the three genes discovered as responsible for familial hemiplegic migraine (FHM) are not involved in the typical migraines. Accordingly, we propose to consider FHM as a syndromic migraine and not as a variety of MA. Moreover, we suggest that epigenetic mechanisms play a role in the determination of the typical migraines, and that the primary headaches represent behavioural responses (sickness behaviour, fight-or-flight responses), having adaptive advantage and having been evolutionary conserved, in which pain represents a signal of homeostatic imbalance. Epigenetic mechanisms and this proposed genetic behavioural model could be usefully incorporated into headache genetic research.
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