Perrone et al. Int J Pathol Clin Res 2019, 5:085 Volume 5 | Issue 1 DOI: 10.23937/2469-5807/1510085 ISSN: 2469-5807 International Journal of Pathology and Clinical Research Open Access Citaton: Perrone L, Daltoé FP, Araújo LCA, Nunes FD, Gallotni MHC, et al. (2019) Clinical and Genetcs Findings in Möbius Syndrome: Role of Hoxa1 and Hoxb1 Mutatons. Int J Pathol Clin Res 5:085. doi. org/10.23937/2469-5807/1510085 Accepted: January 12, 2019: Published: January 14, 2019 Copyright: © 2019 Perrone L, et al. This is an open-access artcle distributed under the terms of the Creatve Commons Atributon License, which permits unrestricted use, distributon, and reproducton in any medium, provided the original author and source are credited. Perrone et al. Int J Pathol Clin Res 2019, 5:085 • Page 1 of 10 • Clinical and Genetcs Findings in Möbius Syndrome: Role of Hoxa1 and Hoxb1 Mutatons Lineu Perrone Jr 1 , Felipe Perozzo Daltoé 1,2 , Luiz Carlos Areas Araújo 3 , Fabio Daumas Nunes 1 , Marina Helena Cury Gallotni 1 and Andrea Mantesso 1 1 Department of Oral Pathology, School of Dentstry, University of Sao Paulo, Sao Paulo, Brazil 2 Department of Pathology, Federal University of Santa Catarina, Florianopolis, Brazil 3 Fleury Insttute, Sao Paulo, Brazil *Corresponding author: Felipe Perozzo Daltoé, MSD, PhD, Department of Oral Pathology, School of Dentstry, University of Sao Paulo; Department of Pathology, Health Sciences Center, Federal University of Santa Catarina, Street Defno Conte, University Campus, Trindade, 88040-900, Florianópolis, SC, Brazil, Tel: +55-48-3207-5068 Abstract Möbius syndrome (MBS) is a rare congenital neurological disorder typically characterized by the absence or underde- velopment 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 identifed 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 resem- bles features of the clinical profle 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 his- tory and MBS by comparing the presence of polymorphisms in the compromised individuals with those found in their rel- atives and in unrelated people. Furthermore, we investigat- ed 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 intercur- rences and use of misoprostol in patients’ phenotype. Our results do not establish a clear link between a specifc mu- tation 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. Keywords Möbius syndrome, Hoxa1, Hoxb1, Misoprostol Introducton Möbius syndrome (MBS) is a congenital unilateral or bilateral palsy of the abducens (VI) and facial (VII) cranial nerves. This disorder can be associated with palsy of other cranial nerves such as the trigeminal (V), glossopharyngeal (IX) and/or hypoglossal nerve (XII). Other malformatons such as craniofacial and orofacial anomalies (e.g., clef palate, abnormalites of the tongue, micrognathia), and limb malformatons (e.g., ectrodactyly, syndactyly, arthrogryposis) can occur concurrently with MBS [1]. The precise etology and pathogenesis of the syndrome are uncertain. The most accepted pathogenic mechanism is a circulatory disorder at early stages of development. In most cases, no genetc etology has been identfed but familial occurrence has been described [2]. Mutatons in Hoxa1 and Hoxb1 genes have been proposed to play a role in the development of MBS [3-5] but in Brazil, an environmental cause such as the use of abortfacients like misoprostol also has been described [6,7]. Brazilian law bans aborton except in special condi- OrigiNAL ArtiCLe Check for updates