Cluster headache is an inherited disorder in some families

We investigated the familial occurrence of cluster headache in 370 probands with cluster headache, diagnosed according to the operational diagnostic criteria of the International Headache Society. Seven probands belonged to three families. A positive family history of cluster headache was found in 7% (25 of 366) of the families. Compared with the general population, the first- and second-degree relatives of the 370 probands with cluster headache had a 14- and 2-fold increased risk of having cluster headache, after standardization for sex and age. This increased familial risk strongly suggests that cluster headache has a genetic cause. The patterns of segregation were assessed by complex segregation analysis performed with the computer program, POINTER. The segregation analysis suggests that cluster headache has an autosomal dominant gene with a penetrance of 0.30 to 0.34 in males and 0.17 to 0.21 in females. The gene is present in 3% to 4% of males and 7% to 10% of females with cluster headache.