Wang Shengjie, Qin Qiaozhen, Jiang Deyue, Xiao Yan, Ye Lingtong, Jiang Xiaoxia, Guo Qinghua
Department of Endocrinology, The First Medical Center, Chinese PLA General Hospital, Beijing, China.
Beijing Institute of Basic Medical Sciences, Beijing, China.
Front Endocrinol (Lausanne). 2024 Feb 23;15:1338781. doi: 10.3389/fendo.2024.1338781. eCollection 2024.
Pituitary stalk interruption syndrome (PSIS) is a complex clinical syndrome characterized by varied pituitary hormone deficiencies, leading to severe manifestations across multiple systems. These include lifelong infertility, short stature, mental retardation, and potentially life-threatening pituitary crises if not promptly diagnosed and treated. Despite extensive research, the precise pathogenesis of PSIS remains unclear. Currently, there are two proposed theories regarding the pathogenic mechanisms: the genetic defect theory and the perinatal injury theory.
We systematically searched English databases (PubMed, Web of Science, Embase) and Chinese databases (CNKI, WanFang Med Online, Sinomed) up to February 24, 2023, to summarize studies on gene sequencing in PSIS patients. Enrichment analyses of reported mutated genes were subsequently performed using the Metascape platform.
Our study included 37 articles. KEGG enrichment analysis revealed mutated genes were enriched in the Notch signaling pathway, Wnt signaling pathway, and Hedgehog signaling pathway. GO enrichment analysis demonstrated mutated genes were enriched in biological processes such as embryonic development, brain development, axon development and guidance, and development of other organs.
Based on our summary and analyses, we propose a new hypothesis: disruptions in normal embryonic development, partially stemming from the genetic background and/or specific gene mutations in individuals, may increase the likelihood of abnormal fetal deliveries, where different degrees of traction during delivery may lead to different levels of pituitary stalk interruption and posterior lobe ectopia. The clinical diversity observed in PSIS patients may result from a combination of genetic background, specific mutations, and variable degrees of traction during delivery.
垂体柄中断综合征（PSIS）是一种复杂的临床综合征，其特征为多种垂体激素缺乏，可导致多个系统出现严重表现。这些表现包括终身不孕、身材矮小、智力发育迟缓，若不及时诊断和治疗，还可能引发危及生命的垂体危象。尽管进行了广泛研究，但PSIS的确切发病机制仍不清楚。目前，关于致病机制有两种提出的理论：基因缺陷理论和围产期损伤理论。
我们系统检索了截至2023年2月24日的英文数据库（PubMed、Web of Science、Embase）和中文数据库（中国知网、万方医学网、中国生物医学文献数据库），以总结PSIS患者基因测序的研究。随后使用Metascape平台对报道的突变基因进行富集分析。
我们的研究纳入了37篇文章。KEGG富集分析显示突变基因在Notch信号通路、Wnt信号通路和Hedgehog信号通路中富集。GO富集分析表明突变基因在胚胎发育、脑发育、轴突发育和导向以及其他器官发育等生物学过程中富集。
基于我们的总结和分析，我们提出一个新的假说：正常胚胎发育的中断，部分源于个体的遗传背景和/或特定基因突变，可能增加异常分娩的可能性，分娩过程中不同程度的牵拉可能导致不同程度的垂体柄中断和后叶异位。PSIS患者中观察到的临床多样性可能是遗传背景、特定突变以及分娩时不同程度牵拉共同作用的结果。
