journal article Mar 08, 2017

Genetics of Migraine: Insights into the Molecular Basis of Migraine Disorders

View at Publisher Save 10.1111/head.13053
Abstract
Migraine is a complex, debilitating neurovascular disorder, typically characterized by recurring, incapacitating attacks of severe headache often accompanied by nausea and neurological disturbances. It has a strong genetic basis demonstrated by rare migraine disorders caused by mutations in single genes (monogenic), as well as familial clustering of common migraine which is associated with polymorphisms in many genes (polygenic). Hemiplegic migraine is a dominantly inherited, severe form of migraine with associated motor weakness. Family studies have found that mutations in three different ion channels genes,
CACNA1A
,
ATP1A2
, and
SCN1A
can be causal. Functional studies of these mutations has shown that they can result in defective regulation of glutamatergic neurotransmission and the excitatory/inhibitory balance in the brain, which lowers the threshold for cortical spreading depression, a wave of cortical depolarization thought to be involved in headache initiation mechanisms. Other putative genes for monogenic migraine include
KCKN18
,
PRRT2
, and
CSNK1D
, which can also be involved with other disorders. There are a number of primarily vascular disorders caused by mutations in single genes, which are often accompanied by migraine symptoms. Mutations in
NOTCH3
causes cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary cerebrovascular disease that leads to ischemic strokes and dementia, but in which migraine is often present, sometimes long before the onset of other symptoms. Mutations in the
TREX1
and
COL4A1
also cause vascular disorders, but often feature migraine. With respect to common polygenic migraine, genome‐wide association studies have now identified single nucleotide polymorphisms at 38 loci significantly associated with migraine risk. Functions assigned to the genes in proximity to these loci suggest that both neuronal and vascular pathways also contribute to the pathophysiology of common migraine. Further studies are required to fully understand these findings and translate them into treatment options for migraine patients.
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Cited By
108
Neuroscience & Biobehavioral Re...
Metrics
108
Citations
216
References
Details
Published
Mar 08, 2017
Vol/Issue
57(4)
Pages
537-569
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Cite This Article
Heidi G. Sutherland, Lyn R. Griffiths (2017). Genetics of Migraine: Insights into the Molecular Basis of Migraine Disorders. Headache: The Journal of Head and Face Pain, 57(4), 537-569. https://doi.org/10.1111/head.13053
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