{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T01:22:25Z","timestamp":1773796945034,"version":"3.50.1"},"reference-count":62,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms26094217","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T07:49:36Z","timestamp":1745912976000},"page":"4217","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Etiology of Moebius Syndrome\u2014Making the Case for Animal Models"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8469-2404","authenticated-orcid":false,"given":"Manuela-Petronela","family":"Tracicaru","sequence":"first","affiliation":[{"name":"Department of Morphofunctional Sciences, Anatomy and Embryology, Grigore T. Popa University of Medicine and Pharmacy Ia\u0219i, University Street No 16, 700115 Ia\u0219i, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5182-3967","authenticated-orcid":false,"given":"Rare\u0219-Vasile","family":"Tracicaru","sequence":"additional","affiliation":[{"name":"Department of Morphofunctional Sciences, Anatomy and Embryology, Grigore T. Popa University of Medicine and Pharmacy Ia\u0219i, University Street No 16, 700115 Ia\u0219i, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9856-6496","authenticated-orcid":false,"given":"Delia","family":"H\u00eenganu","sequence":"additional","affiliation":[{"name":"Department of Morphofunctional Sciences, Anatomy and Embryology, Grigore T. Popa University of Medicine and Pharmacy Ia\u0219i, University Street No 16, 700115 Ia\u0219i, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marius Valeriu","family":"H\u00eenganu","sequence":"additional","affiliation":[{"name":"Department of Morphofunctional Sciences, Anatomy and Embryology, Grigore T. Popa University of Medicine and Pharmacy Ia\u0219i, University Street No 16, 700115 Ia\u0219i, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1002\/ajmg.a.60683","article-title":"Will the real Moebius syndrome please stand up? A systematic review of the literature and statistical cluster analysis of clinical features","volume":"179","author":"Bell","year":"2019","journal-title":"Am. J. Med. Genet. 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