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Cluster headache (CH) is a debilitating condition with severe and recurrent headaches characterized by circannual and circadian rhythms. A genetic contingent was suggested, and several loci were described in large cohorts. However, no variant associated with CH for multiplex families has been described. The purpose of our study was to examine candidate genes and new genetic variants in a multigenerational family of cluster headaches in which two members have original chronobiological characteristics that we have called the phenomenon of “family periodicity”.