Clinical and Genetics Findings in Möbius Syndrome: Role of Hoxa1 and Hoxb1 Mutations

Abstract

Möbius syndrome (MBS) is a rare congenital neurological disorder typically characterized by the absence or underdevelopment of the 6th and 7 th cranial nerves, causing a loss of facial expression and strabismus. Other cranial nerves may be affected in addition to other structures such as the jaw, limbs, and anterior chest. While the primary cause of MBS has not yet been identified different hypotheses have been enumerated, including a possible genetic alteration. The Hoxb1 gene may be a good candidate as mutations of the gene in animals yield a phenotype closely resembles features of the clinical profile associated with humans suffering from MBS. Another good candidate gene may be Hoxa1 giving its implications in the development of the hindbrain, cranial nerves and ear in a possible functional synergy with Hoxb1. In this study we analyzed mutations in Hoxb1 and in its paralogue Hoxa1 in 29 MBS patients and also analyzed the feasible correlation between familial history and MBS by comparing the presence of polymorphisms in the compromised individuals with those found in their relatives and in unrelated people. Furthermore, we investigated whether the incidence of polymorphisms is associated with the severity of the patient`s phenotype and whether the presence of polymorphisms is correlated with pregnancy intercurrences or the use of misoprostol during gestation. Finally, we investigated the effects of pregnancy intercurrences and use of misoprostol in patients' phenotype. Our results do not establish a clear link between a specific mutation and the others parameter analyzed concluding that the complex pattern of development of MBS stems from a heterogeneous etiology, which involves both genetic and environmental aspects.

Clinical and Genetic Correlation in Neurocristopathies: Bridging a Precision Medicine Gap

“…Disruption, therefore, of WNT signaling renders nerve abnormalities like those in MBS probable. The implication of HOX family genes, which are key genes in the morphogenesis of the cranial neural crest, is also likely, with emphasis on HOXA1 and HOXB1 [127,131,132]. Mutations in PLXND1 and REV3L account for a percentage of MBS patients.…”