Familial cluster headache in an Italian case series

To investigate the familial occurrence of cluster headache (CH) in a series of Italian patients, we focused on possible differences in the mean age of onset between familial and non-familial CH cases. We considered all consecutive patients referred to the Parma Headache Centre between 1975 and 2013 affected by CH; we subsequently reviewed these cases applying the ICHD3-beta criteria (785 probands, 569 men and 216 women). We identified those cases who reported at least a first-degree relative with a diagnosis of CH, which was confirmed by the clinical documentation they provided. Each one of the "familial cases" was matched by sex and age (±2 years) at the first visit to three consecutive CH patients who did not report any first-degree relative affected by CH. A positive family history of CH was found in 40 probands (5.1 %), 28 men (4.9 %), and 12 women (5.6 %). The male:female ratio was 2.3:1 among the 40 CH familial cases, while it was 2.7:1 among all the CH non-familial cases (745 patients). The mean age of onset was significantly (p < 0.01) lower in women with familial CH (28.5 years, SD 17.7 years, range 10-63 years) than in women with non-familial CH (46.7 years, SD 13.7 years, range 11-74 years); we did not find a significant age difference among men (the mean age of onset for the familial cases was 29.6 years, SD 13.6 years, range 6-63 years; while for the non-familial cases, it was 29.3 years, SD 13.2 years, range 13-59 years). Our study suggests that genetic factors may play a role in the female gender causing an earlier age of onset and a lower male-to-female sex ratio in familial cases.