Möbius syndrome (MBS) is a neurological disorder that is characterized by paralysis of the facial nerves and variable other congenital anomalies. The aetiology of this syndrome has been enigmatic since the initial descriptions by von Graefe in 1880 and by Möbius in 1888, and it has been debated for decades whether MBS has a genetic or a non-genetic aetiology. Here, we report de novo mutations affecting two genes, PLXND1 and REV3L in MBS patients. PLXND1 and REV3L represent totally unrelated pathways involved in hindbrain development: neural migration and DNA translesion synthesis, essential for the replication of endogenously damaged DNA, respectively. Interestingly, analysis of Plxnd1 and Rev3l mutant mice shows that disruption of these separate pathways converge at the facial branchiomotor nucleus, affecting either motoneuron migration or proliferation. The finding that PLXND1 and REV3L mutations are responsible for a proportion of MBS patients suggests that de novo mutations in other genes might account for other MBS patients.
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Genes (Basel)
July 2024
Medical Genetics, Department of Health Sciences, Università degli Studi di Milano, 20142 Milan, Italy.
Moebius syndrome (MBS) is a rare congenital disorder characterized by non-progressive facial palsy and ocular abduction paralysis. Most cases are sporadic, but also rare familial cases with autosomal dominant transmission and incomplete penetrance/variable expressivity have been described. The genetic etiology of MBS is still unclear: de novo pathogenic variants in and are reported in only a minority of cases, suggesting the involvement of additional causative genes.
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Front Genet
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Center for Genomic Medicine, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona, Sabadell, Spain.
Moebius Syndrome (MBS) is a rare congenital neurological disorder characterized by paralysis of facial nerves, impairment of ocular abduction and other variable abnormalities. MBS has been attributed to both environmental and genetic factors as potential causes. Until now only two genes, and have been identified to cause MBS.
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Pediatr Neurol
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Facultad Mexicana de Medicina, Universidad La Salle, Mexico City, Mexico. Electronic address:
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.
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Wilhelm Johannsen Center for Functional Genome Research, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
Moebius syndrome (MBS) is a congenital disorder caused by paralysis of the facial and abducens nerves. Although a number of candidate genes have been suspected, so far only mutations in PLXND1 and REV3L are confirmed to cause MBS. Here, we fine mapped the breakpoints of a complex chromosomal rearrangement (CCR) 46,XY,t(7;8;11;13) in a patient with MBS, which revealed 41 clustered breakpoints with typical hallmarks of chromothripsis.
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Cold Spring Harb Mol Case Stud
March 2017
Department of Pediatrics, University of Montreal, Montreal, Quebec H3T 1C5, Canada.
Moebius syndrome is characterized by congenital unilateral or bilateral facial and abducens nerve palsies (sixth and seventh cranial nerves) causing facial weakness, feeding difficulties, and restricted ocular movements. Abnormalities of the chest wall such as Poland anomaly and variable limb defects are frequently associated with this syndrome. Most cases are isolated; however, rare families with autosomal dominant transmission with incomplete penetrance and variable expressivity have been described.
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