Inheritance of Cluster Headache and its Possible Link to Migraine

SYNOPSIS We evaluated the possibility that cluster headache may be a transmitted disorder, influenced by migraine genetics. In the first part of a two part study, 24 female cluster headache probands having at least one first degree relative with cluster headache were evaluated for familial histories of cluster and migraine headache. Headache histories of most parents, sib‐lings and children were satisfactorily documented by either direct interview or by information provided by knowledgeable relatives. In approximately a third of relatives, the headache history could not be properly ascertained. The second part of the study evaluated occurrence rates of cluster and migraine headaches among first degree relatives of 200 female and 100 male cluster headache patients, and the proportion of affected relatives. These data were compared to those of 200 women and 100 men with migraine headache; family history data were, for the most part, provided by headache patients. Twenty‐four of two hundred cluster headache women (12%) had at least one first degree relative with cluster headache. Three generations of cluster headache were found in 7/ 24 kindreds (29.17%). Parental cluster headache was found in 19 of the 24 probands (79.17%); in 14/19 (73.68%), transmission was from father to proband. Fifty percent of cluster pro‐bands also had migraine headaches, and almost 50% had a family history of migraine. Similarly, of the larger population of 300 cluster patients, approximately 45% had a positive family history of migraine. Of 1652 relatives of all cluster patients, 3.45% had cluster headache (thirteen times the expected frequency of cluster headache in the general population) and 17.55% had migraine headaches. The combined occurrence rate of cluster and migraine headaches among mothers or fathers of cluster patients differed little from the parents of migraine patients (X 2 = 3.16, P <.10; X 2 = 0.28, P < 0.70, respectively). Migraine was significantly more common, however, among some relatives of migraineurs compared to combined frequencies of migraine and cluster headache among relatives of cluster patients. Finally, the migraine population of Goodell et al. 28 was compared to our cluster headache population for occurrence of either headache type among children where neither, one or both parents had headaches. The results for our cluster population was 36.33%, 48.07% and 71.43%, respectively; this distribution was not significantly different from the migraine group of Goodell et al. (28.6%, 44.2% and 69.2%), 28 and conformed to a Mendelian pattern of transmission (X 2 = 37.55, P < 0.001). Results of this study provided evidence suggesting a genetic basis for cluster headache. Equally compellingwere findings suggesting a genetic link between migraine and cluster headaches. The authors have speculatedthat migraine and cluster headache may be the same disorder, genotypically, but expression of the latter mayinvolve a more complex process requiring, as yet unknown, extrinsic or intrinsic influences.