Cluster Headache: What Role Does Family History Play?

Cluster headache appears to be an inherited disorder in a subset of families and is likely associated with multiple hereditary patterns, according to a new systematic review of 40 articles.

“Overall, this systematic review supports the notion that familial cluster headache is likely the result of multiple susceptibility genes, as well as environmental factors,” the authors of the review wrote.

Data for the systematic review, which included publications from 1985 to 2016, were obtained from PubMed, Embase, and Cochrane Library. A total of 22 large cohort studies, 1 twin-based study, and 17 case reports or small case series were included in the analysis.

The rate of positive family history of cluster headache ranged from 0% to 22% (median 8.2%) among the 22 large cohort studies. In the 5 largest studies, positive family history of cluster headache was observed in the following proportions:

  • 18.0% (no numerator provided) of 1134 probands
  • 40 of 785 cases (5.1%)
  • 10.0% (no numerator provided) of 693 probands
  • 12 of 609 cases (2.0%)
  • 56 of 500 cases (11.2%; no numerator provided)

The researchers noted that, due to differences in methodologies, a meta-analysis was not performed. Other notable findings included:

  • In one twin-based study (n = 37 twin pairs), a concordance rate of 5.4% (2 pairs) was observed.
  • A total of 67 pedigrees were identified, and the majority of pedigrees (46 of 67 [69%]) appeared to have an autosomal dominant pattern, except for 19 of 67 (28%) that appeared to have an autosomal recessive pattern.
  • A total of 10 pedigrees of probable or atypical cluster headache were identified, and all of these pedigrees appeared to have an autosomal dominant pattern.
  • Among affected men and boys, the sex ratio for cluster headache was 1.39 (103:74) compared with affected women and girls. The researchers noted that this ratio is lower than that of the general population living with cluster headache.

“Cluster headache is an inherited disorder in a subset of families and is associated with multiple hereditary patterns,” the researchers concluded.

“There is an unexpectedly high preponderance of women and girls with familial cluster headache; genetic subanalyses limited to female participants are necessary to further explore this observation, because these data are otherwise masked by the higher numbers of male participants with cluster headache,” they added.

—Christina Vogt

Waung MW, Taylor A, Qualmann KJ, Burish MJ. Family history of cluster headache: a systematic review [Published online April 20, 2020]. JAMA Neurol. doi:10.1001/jamaneurol.2020.0682