Department of Biomedical Sciences, University of Cape Coast, Cape Coast, Ghana.
Center for American Indian and Rural Health Equity, Montana State University, Bozeman, MT, USA.
Yale J Biol Med. 2021 Dec 29;94(4):657-672. eCollection 2021 Dec.
Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a disorder caused by Müllerian ducts dysgenesis affecting 1 in 5000 women with a typical 46,XX karyotype. The etiology of MRKH syndrome is complex and largely unexplained. Familial clustering suggests a genetic component and the spectrum of clinical presentations seems consistent with an inheritance pattern characterized by incomplete penetrance and variable expressivity. Mutations of several candidate genes have been proposed as possible causes based on genetic analyses of human patients and animal models. In addition, studies of monozygotic twins with discordant phenotypes suggest a role for epigenetic changes following potential exposure to environmental compounds. The spectrum of clinical presentations is consistent with intricate disruptions of shared developmental pathways or signals during early organogenesis. However, the lack of functional validation and translational studies have limited our understanding of the molecular mechanisms involved in this condition. The clinical management of affected women, including early diagnosis, genetic testing of MRKH syndrome, and the implementation of counseling strategies, is significantly impeded by these knowledge gaps. Here, we illustrate the embryonic development of tissues and organs affected by MRKH syndrome, highlighting key pathways that could be involved in its pathogenesis. In addition, we will explore the genetics of this condition, as well as the potential role of environmental factors, and discuss their implications to clinical practice.
苗勒管发育不全综合征（MRKH 综合征）是一种由米勒管发育不全引起的疾病，影响 5000 名女性中的 1 名，其典型核型为 46，XX。MRKH 综合征的病因复杂，很大程度上尚未阐明。家族聚集表明存在遗传成分，临床表现谱似乎与不完全外显率和可变表达率为特征的遗传模式一致。基于对人类患者和动物模型的遗传分析，已提出几种候选基因的突变可能是其病因。此外，对表现型不一致的同卵双胞胎的研究表明，在潜在暴露于环境化合物后，表观遗传变化可能起作用。临床表现谱与早期器官发生过程中共同发育途径或信号的复杂中断一致。然而，缺乏功能验证和转化研究限制了我们对涉及该病症的分子机制的理解。受影响女性的临床管理，包括早期诊断、MRKH 综合征的基因检测以及咨询策略的实施，受到这些知识空白的严重阻碍。在这里，我们展示了受 MRKH 综合征影响的组织和器官的胚胎发育，强调了可能参与其发病机制的关键途径。此外，我们将探讨该病症的遗传学以及环境因素的潜在作用，并讨论其对临床实践的影响。
