Mayer-Rokitansky-Küster-Hauser(MRKH)综合征是一种由苗勒管发育不良引起的疾病,影响5000名女性中的1名,具有典型的46,XX核型。MRKH综合征的病因复杂且在很大程度上无法解释。家族聚类表明遗传成分和临床表现的范围似乎与以不完全外显率和可变表现力为特征的遗传模式一致。基于人类患者和动物模型的遗传分析,已经提出了几种候选基因的突变作为可能的原因。此外,对表型不一致的单卵双胞胎的研究表明,潜在暴露于环境化合物后的表观遗传变化具有作用。临床表现的范围与早期器官发生过程中共享发育途径或信号的复杂破坏一致。然而,缺乏功能验证和翻译研究限制了我们对这种情况涉及的分子机制的理解.受影响妇女的临床管理,包括早期诊断,MRKH综合征基因检测,以及咨询策略的实施,受到这些知识差距的严重阻碍。这里,我们说明了受MRKH综合征影响的组织和器官的胚胎发育,强调可能涉及其发病机制的关键途径。此外,我们将探索这种情况的遗传学,以及环境因素的潜在作用,并讨论它们对临床实践的影响。
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.