Genetics of cluster headache.

Cluster headache (CH) is a rare, excruciating primary headache disorder. A genetic basis has been suggested by family and twin studies, but the mode of transmission seems to vary and the amount of heritability is unclear. The number of genetic association studies investigating variants implicated in the pathophysiology of CH is limited. The HCRTR2 1246G > A and the ADH4 925A > G polymorphisms have been associated with CH. The former has been confirmed and may affect the hypothalamic hypocretin system. However, it only appears to account for a part of the genetic susceptibility for CH, and additional genetic and environmental factors are likely implicated. Pharmacogenetic studies have suggested that the GNB3 825C > T polymorphism may modify treatment response to triptans among CH patients by altering the signal transduction cascade via G protein-coupled receptors. Genetic studies in CH are notoriously difficult due to the complex nature of the disorder and the low prevalence of CH.