Study on Moebius Syndrome and Congenital Facial Weakness Disorders

This is a natural history study with a cross-sectional design of Moebius syndrome (MIM 157900), a heterogeneous developmental disorder defined as a congenital, non-progressive facial weakness with limited abduction of one or both eyes, often associated with additional features such as other cranial nerve dysfunction, craniofacial, skeletal and limb deformities, as well as intellectual or behavioral impairments. In this study we will attempt to characterize the clinical phenotype of Moebius and associated congenital facial weakness syndromes, collect thorough information on possible prenatal environmental exposures and use genetic studies, including whole exome sequencing, on DNA from patients and family members of patients to identify disease-causing genes. We will also conduct brain magnetic resonance- and diffusion tensor imaging- studies in these patients in order to explore brainstem and cranial nerve structure and associated white matter tract anomalies. Through this combined clinical, molecular and imaging approach, we anticipate that phenotype-genotype correlations will be revealed. These results will lead to new insights into the clinical definition of these conditions, molecular pathways, and potential networks involved in the pathogenesis of facial weakness and associated multisystem dysmorphogenesis. Our population will consist of patients, ages 2 to 80 years, inclusive of any gender, race, or ethnic group, with congenital facial palsy, isolated or combined with other congenital anomalies, and their families. We will continue to recruit approximately 24 probands each year, ages 2 to 80 years, inclusive of any gender, race, or ethnic group, and their parents and unaffected family members for a total of 72 patients/families. In most cases, patients will be referred through the Moebius Syndrome Foundation, a patient organization with a current membership of 2000 people in its database, 1400 of whom have been diagnosed with Moebius syndrome. Outcome measures will include the results from a battery of clinical evaluations, including ophthalmology, audiology, neurology, psychiatry, and rehabilitative medicine. Patients will also undergo neurocognitive and autism screening assessments, electromyography/nerve conduction, and blink reflex studies. Imaging and genetic studies will provide the most robust data for analysis in this study. A skin biopsy may be performed on some patients in order to culture fibroblasts for additional biochemical, cell biological, and molecular analyses.