Tracicaru Manuela-Petronela, Tracicaru Rareș-Vasile, Hînganu Delia, Hînganu Marius Valeriu
Department of Morphofunctional Sciences, Anatomy and Embryology, Grigore T. Popa University of Medicine and Pharmacy Iași, University Street No 16, 700115 Iași, Romania.
Int J Mol Sci. 2025 Apr 29;26(9):4217. doi: 10.3390/ijms26094217.
Moebius syndrome (MBS) is a rare disease consisting of uni-/bilateral palsy of CN VI and VII without impairment of vertical eye movements. Its uncommon nature means that the etiology is still uncertain. It is thought to be caused by vascular lesions leading to infarction in the nuclei of cranial nerves VI and VII on the posterior aspect of the pons. However, several genes have also been discussed as possibly causative. We performed a literature search in the PUBMED database and on the Science Direct platform with terms related to the pathology and to each etiology individually. Included were original papers and review articles published in peer-reviewed international journals and reference books and databases on the subjects discussed. We excluded articles not published in English, conference communications, dissertations, monographs, and other non-peer-reviewed forms of publication. The total number of publications thus included was 62. This review discusses the functions of the three most related genes found in recent research (PLXND1, REV3L, TUBB3) and the results of animal studies focusing on their mutations. We note that the PLXND1 and REV3L mutations have been most associated with MBS and that the current studies on their function suggest histological lesions similar to the target disease, albeit without clear phenotypic expression. We ascertain that TUBB3 mutations are mostly related to CEFOM3, which is a differential diagnosis for MBS. Regarding the vascular etiology, we review the types of lesions involved and discuss their timing in relation to embryologic stages. We also highlight the main investigation methods available. A multitude of the factors discussed might be causative of MBS, and we thus consider it necessary to attempt the development of an animal model for the disease. To this end, we propose the development of transgenic mice models containing the single nucleotide mutations documented in human patients, and we discuss the use of the chick embryo model for the vascular etiology.
梅比乌斯综合征（MBS）是一种罕见疾病，表现为单侧/双侧第六和第七脑神经麻痹，垂直眼球运动不受影响。其罕见性意味着病因仍不明确。据认为，它是由血管病变导致脑桥后部第六和第七脑神经核梗死引起的。然而，也有几种基因被讨论可能是致病原因。我们在PUBMED数据库和科学Direct平台上进行了文献检索，检索词分别与病理学以及每种病因相关。纳入的文献包括在同行评审的国际期刊上发表的原创论文和综述文章，以及关于所讨论主题的参考书和数据库。我们排除了非英文发表的文章、会议交流论文、学位论文、专著以及其他非同行评审的出版物形式。如此纳入的出版物总数为62篇。本综述讨论了近期研究中发现的三个最相关基因（PLXND1、REV3L、TUBB3）的功能以及聚焦于其突变的动物研究结果。我们注意到PLXND1和REV3L突变与MBS的关联最为密切，目前对其功能的研究表明存在与目标疾病相似的组织学病变，尽管没有明确的表型表达。我们确定TUBB3突变大多与CEFOM3相关，CEFOM3是MBS的一种鉴别诊断。关于血管病因，我们回顾了所涉及的病变类型，并讨论了它们与胚胎发育阶段相关的发生时间。我们还强调了现有的主要研究方法。所讨论的众多因素可能是MBS的病因，因此我们认为有必要尝试开发该疾病的动物模型。为此，我们提议开发包含人类患者记录的单核苷酸突变的转基因小鼠模型，并讨论将鸡胚模型用于血管病因研究。
