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. 2008 Mar 15;9(2):57–69. doi: 10.1007/s10194-008-0026-x

The primary headaches: genetics, epigenetics and a behavioural genetic model

Pasquale Montagna 1,✉
PMCID: PMC2276243  PMID: 18345478

Abstract

The primary headaches, migraine with (MA) and without aura (MO) and cluster headache, all carry a substantial genetic liability. Familial hemiplegic migraine (FHM), an autosomal dominant mendelian disorder classified as a subtype of MA, is due to mutations in genes encoding neural channel subunits. MA/MO are considered multifactorial genetic disorders, and FHM has been proposed as a model for migraine aetiology. However, a review of the genetic studies suggests that the FHM genes are not involved in the typical migraines and that FHM should be considered as a syndromic migraine rather than a subtype of MA. Adopting the concept of syndromic migraine could be useful in understanding migraine pathogenesis. We hypothesise that epigenetic mechanisms play an important role in headache pathogenesis. A behavioural model is proposed, whereby the primary headaches are construed as behaviours, not symptoms, evolutionarily conserved for their adaptive value and engendered out of a genetic repertoire by a network of pattern generators present in the brain and signalling homeostatic imbalance. This behavioural model could be incorporated into migraine genetic research.

Keywords: Migraine, Tension-type headache, Cluster headache, Genetics, Epigenetics

Full Text

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Acknowledgments

I wish to thank Ms. A. Laffi for help with the manuscript, and A. Collins for revising the English text. Supported by MIUR grants. This review results from the lesson of the Author at the Master in Headache Medicine, Sapienza University of Rome, during the Academic Year 2007–2008.

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