Towards an understanding of the aetiology, genomic landscape and management of Moebius syndrome

Moebius Syndrome (MBS) is a rare neurodevelopmental disorder characterised by facial paralysis and ocular motility defects. Its origins trace back to the 19th century, with its clinical delineation attributed to German neurologist Paul M & ouml;bius. The syndrome presents with a spectrum of variable systemic clinical features, necessitating a multidisciplinary approach to diagnosis and management. The prevalence of MBS has been estimated to range between 1 in 50,000 to 1 in 500,000 individuals, with a universal distribution across ethnicities and genders. The aetiology of MBS is poorly understood but is likely multifactorial, with developmental, genetic, and environmental factors playing roles. Recent research has identified potential genetic contributors, REV3L and PLXND1, but further work is needed to elucidate the genetic landscape of this rare neurodevelopmental disorder. Here we describe the current understanding of the clinical features, aetiology, genetic landscape, and management of MBS, emphasising the importance of early diagnosis and a holistic approach to patient care. We also propose a set of criteria aimed at standardising MBS reporting to enhance information sharing and bolster MBS research initiatives. Collaborative research efforts in the future hold the potential to offer transformative insights and improved outcomes for affected individuals and their families.