Physiopathologic Bases of Moebius Syndrome: Combining Genetic, Vascular, and Teratogenic Theories

Pediatr Neurol. 2024 Apr:153:1-10. doi: 10.1016/j.pediatrneurol.2024.01.007. Epub 2024 Jan 11.

Abstract

Moebius syndrome (MBS) is a congenital cranial dysinnervation disorder (CCDD) characterized by a bilateral palsy of abducens and facial cranial nerves, which may coexist with other cranial nerves palsies, mostly those found in the dorsal pons and medulla oblongata. MBS is considered a "rare" disease, occurring in only 1:50,000 to 1:500,000 live births, with no gender predominance. Three independent theories have been described to define its etiology: the vascular theory, which talks about a transient blood flow disruption; the genetic theory, which takes place due to mutations related to the facial motor nucleus neurodevelopment; and last, the teratogenic theory, associated with the consumption of agents such as misoprostol during the first trimester of pregnancy. Since the literature has suggested the existence of these theories independently, this review proposes establishing a theory by matching the MBS molecular bases. This review aims to associate the three etiopathogenic theories at a molecular level, thus submitting a combined postulation. MBS is most likely an underdiagnosed disease due to its low prevalence and challenging diagnosis. Researching other elements that may play a key role in the pathogenesis is essential. It is common to assume the difficulty that patients with MBS have in leading an everyday social life. Research by means of PubMed and Google Scholar databases was carried out, same in which 94 articles were collected by using keywords with the likes of "Moebius syndrome," "PLXND1 mutations," "REV3L mutations," "vascular disruption AND teratogens," and "congenital facial nerve palsy." No exclusion criteria were applied.

Keywords: Congenital palsy; Facial nerve palsy; Moebius syndrome; Moebius syndrome pathophysiology; Neuronal migration; PI3/Akt signaling; PLXND1 mutation; Vascular pattern disruption.

Publication types

  • Review

MeSH terms

  • DNA-Binding Proteins / genetics
  • DNA-Directed DNA Polymerase / genetics
  • Facial Nerve
  • Facial Paralysis*
  • Humans
  • Mobius Syndrome* / diagnosis
  • Mobius Syndrome* / genetics
  • Mutation
  • Teratogens / toxicity

Substances

  • Teratogens
  • REV3L protein, human
  • DNA-Directed DNA Polymerase
  • DNA-Binding Proteins