Clinical intra- and interfamilial variability of cluster headache.

Our recent description of a 17- and 2-fold increased risk of cluster headache among first- and second-degree relatives, respectively, strongly suggests that cluster headache has a genetic cause. Eighteen families with familial occurrence of cluster headache according to the criteria of the International Headache Society were included. Clinical intra- and interfamilial variability of cluster headaches was analyzed in 44 cases (31 males and 13 females) from 18 families. None of the families showed a distinctive pattern of symptoms except for the two families with chronic cluster headache. Their affected male relatives had a high number (1-8) of attacks per day in their cluster periods. Children had a significantly lower age at onset than parents (p = 0.018), but it is uncertain whether this is a real phenomenon or caused by memory bias. However, the possible existence of anticipation is important in the search for the gene. Co-occurrence of migraine with and without aura was not increased in familial cases of cluster headache compared with the prevalence of migraine with and without aura in the Danish population, implying different etiologies. Our results suggest that episodic, chronic and chronic cluster headaches evolved from episodic have a common etiology and genetic heterogeneity is unlikely on clinical grounds.