Importance Genetic and environmental factors are thought to contribute to cluster headache, and cluster headache can affect multiple members of a family. A thorough understanding of its inheritance is critical to understanding the pathogenesis of this debilitating disease.

Objective To systematically review family history rates and inheritance patterns of cluster headache.

Evidence Review A systematic review was performed in PubMed, Embase, and Cochrane Library. Search criteria were created by a librarian. Articles published between 1985 and 2016, after the publication date of a large review in 1985, were analyzed independently by 2 neurologists to identify family history rates and pedigrees. Pedigrees were analyzed by a genetic counselor.

Findings A total of 1995 studies were found (1988 through the search criteria and 7 through other means). Forty articles met inclusion criteria: 22 large cohort studies, 1 twin-based study, and 17 case reports or small case series. Across the 22 large cohort studies, the positive family history rate of cluster headache varied between 0% and 22%, with a median of 8.2%. The largest 5 studies, of 1134, 785, 693, 609, and 500 probands each, had a positive family history in 18.0% (numerator not provided), 5.1% (40 of 785 cases), 10.0% (numerator not provided), 2.0% (12 of 609 cases), and 11.2% (56 of 500 cases), respectively. No meta-analysis was performed, given differences in methodologies. Separately, 1 twin-based study examined 37 twin pairs and reported a concordance rate of 5.4% (2 pairs). Finally, 67 pedigrees were identified. Most pedigrees (46 of 67 [69%]) were consistent with an autosomal dominant pattern, but 19 of 67 (28%) were consistent with an autosomal recessive inheritance pattern; 10 pedigrees of probable or atypical cluster headache were identified, and all were consistent with an autosomal dominant inheritance pattern. The sex ratio for cluster headache in identified pedigrees was 1.39 (103:74) in affected men and boys compared with affected women and girls, which is lower than that of the general cluster headache population.

Conclusions and Relevance Cluster headache is an inherited disorder in a subset of families and is associated with multiple hereditary patterns. 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. Overall, this systematic review supports the notion that familial cluster headache is likely the result of multiple susceptibility genes as well as environmental factors.

重要性 遗传和环境因素被认为是导致丛集性头痛的原因，而丛集性头痛会影响一个家庭的多个成员。彻底了解其遗传对于了解这种令人衰弱的疾病的发病机理至关重要。

目的 系统回顾家族性头痛的家族史发生率和遗传模式。

证据审查 在PubMed，Embase和Cochrane库中进行了系统的审查。搜索条件由图书馆员创建。在1985年至1985年期间发表大量评论的日期之后，由2位神经科医师独立分析了1985年至2016年之间发表的文章，以确定家族史发生率和血统书。家谱由遗传顾问进行分析。

发现 共发现1995年的研究（1988年通过搜索标准进行研究，7次通过其他方式进行）。40篇符合入选标准的文章：22项大型队列研究，1项基于双胞胎的研究以及17例病例报告或小病例系列研究。在22项大型队列研究中，丛集性头痛的阳性家族史发生率在0％至22％之间，中位数为8.2％。最多的5项研究（分别为1134、785、693、609和500个先证者）的家族史为阳性，分别为18.0％（未提供分子），5.1％（785个案例中的40个），10.0％（未提供分子），分别为2.0％（609例中的12例）和11.2％（500例中的56例）。由于方法不同，没有进行荟萃分析。另外，一项基于双胞胎的研究检查了37对双胞胎，并且报告的一致性率为5.4％（2对）。最终，确定了67个家谱。大多数谱系（67个中的46个[69％]）与常染色体显性遗传模式一致，但67个中的19个（28％）与常染色体隐性遗传模式一致；确定了10个可能的或非典型的丛集性头痛的谱系，且均符合常染色体显性遗传模式。患病男孩和男孩中，已鉴定家系中丛集性头痛的性别比为患病妇女和女孩的1.39（103：74），低于一般丛集性头痛人群的性别比。

结论与相关性 丛集性头痛是一部分家庭的遗传性疾病，与多种遗传模式有关。患有家族性丛集性头痛的妇女和女孩出乎意料地占优势。仅限于女性参与者的遗传子分析对于进一步探索该观察结果是必要的，因为否则这些数据会被簇状头痛的男性参与者更多地掩盖。总的来说，该系统评价支持以下观点：家族性丛集性头痛可能是多种易感基因以及环境因素的结果。