Department of Neurology, University of California, San Francisco, San Francisco.
Houston Methodist Hospital, Houston, Texas.
JAMA Neurol. 2020 Jul 1;77(7):887-896. doi: 10.1001/jamaneurol.2020.0682.
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.
To systematically review family history rates and inheritance patterns of cluster headache.
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.
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.
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.
遗传和环境因素被认为与丛集性头痛有关，而且丛集性头痛可能会影响一个家庭的多个成员。深入了解其遗传方式对于理解这种使人衰弱的疾病的发病机制至关重要。
系统回顾丛集性头痛的家族史发生率和遗传模式。
在 PubMed、Embase 和 Cochrane Library 中进行了系统综述。由一名图书管理员创建了检索标准。分析了 1985 年至 2016 年间发表的文章，这些文章是在 1985 年的一篇大型综述发表后独立由 2 名神经病学家检索的，以确定家族史发生率和系谱。系谱由遗传咨询师进行分析。
共发现 1995 项研究（1988 年通过检索标准和 7 项其他方法）。40 篇文章符合纳入标准：22 项大型队列研究、1 项基于双胞胎的研究和 17 项病例报告或小病例系列。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%。最大的 5 项研究，分别为 1134、785、693、609 和 500 名先证者，阳性家族史发生率分别为 18.0%（分子未提供）、5.1%（785 例中的 40 例）、10.0%（分子未提供）、2.0%（609 例中的 12 例）和 11.2%（500 例中的 56 例）。由于方法学的差异，未进行荟萃分析。另外，1 项基于双胞胎的研究共检查了 37 对双胞胎，报告的一致性率为 5.4%（2 对）。最后，确定了 67 个系谱。大多数系谱（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 个可能或非典型丛集性头痛的系谱，所有这些系谱均与常染色体显性遗传模式一致。在确定的系谱中，丛集性头痛的性别比为 1.39（103 名男性和男孩比 74 名女性和女孩），低于一般丛集性头痛人群。
丛集性头痛是某些家族的遗传疾病，与多种遗传模式有关。家族性丛集性头痛中女性和女孩的比例异常高；需要对仅包括女性参与者的遗传亚分析进行进一步探索，因为这些数据因男性参与者中丛集性头痛的人数较多而被掩盖。总体而言，这项系统综述支持这样一种观点，即家族性丛集性头痛可能是多种易感基因和环境因素共同作用的结果。
