About 8% of people suffering from cluster headache will have a family history of the condition, and the male-to-female ratio is lower than expected in this group of patients, according to a new systematic review.

In general, cluster headache showed multiple inheritance patterns, Dr. Mark J. Burish of The University of Texas Health Science Center at Houston and colleagues found.

"Our study has only been able to tease out that there's not a single gene," Dr. Burish told Reuters Health by phone, noting that some pedigrees suggested autosomal dominant inheritance and others autosomal recessive inheritance. "There are probably different patterns of inheritance with different genes."

Cluster headaches last for 15 to 180 minutes, affect one side of the head, and occur up to eight times a day, Dr. Burish and his colleagues note in JAMA Neurology. They typically first appear in a person's 20s or 30s, and are much more common in males. Previous research found a familial cluster headache rate of about 4%.

Unlike migraines, which last for at least four hours and are made worse by activity, cluster headaches last for three hours or less, and a person feels restless and moves around during the episode.

In the new study, Dr. Burish and his colleagues looked at 40 studies in total, including 22 large cohort studies. Positive family history ranged from 0% to 22% across the cohort studies, with a median of 8.2%..

When they analyzed subgroups of studies, including those with first-person proband diagnosis, those performed at headache centers, those limited to first-degree relatives, those that included interviews with relatives rather than information from proband, those including second- and/or third-degree relatives, and those with more than 500 patients, the family-history rate ranged from a median of 6.7% to 10%.

Sixty-nine percent of the 70 pedigrees analyzed showed autosomal dominant inheritance of cluster headache, while 28% suggested autosomal recessive inheritance.

The ratio of male to female familial cluster headache patients was 1.39, versus 4.3 in the general medical literature. "This difference suggests that factors predisposing men to develop sporadic cluster headache may be different than those that play a role in the pathogenesis of familial cluster headache," the researchers write.

While the findings are helpful for clinicians advising patients, for example parents with cluster headache who want to know how likely their child is to have the condition, Dr. Burish said, it's still not known whether the child will have the same type of headaches, and whether they will begin earlier.

"Unfortunately, we don't have much data on cluster headaches," he said.

"Future genetic studies of familial cluster headache should direct attention to sex differences and headache age at headache onset," he and his colleagues conclude.

SOURCE: https://bit.ly/2xNkHKx JAMA Neurology, online April 20, 2020.