Clinical findings from the landmark MEF2C-related disorders natural history study

Introduction: MEF2C-related disorders are characterized by developmental and cognitive delay, limited language and walking, hypotonia, and seizures. A recent systematic review identified 117 patients with MEF2C-related disorders across 43 studies. Despite these reports, the disorder is not easily recognized and assessments are hampered by small sample sizes. Our objective was to gather developmental and clinical information on a large number of patients. Methods: We developed a survey based on validated instruments and subject area experts to gather information from parents of children with this condition. No personal identifiers were collected. Surveys and data were collected via REDCap and analyzed using Excel and SAS v9.4. Results: Seventy-three parents completed the survey, with 39.7% reporting a MEF2C variant and 54.8% reporting a deletion involving MEF2C. Limited speech (82.1%), seizures (86.3%), bruxism (87.7%), repetitive movements (94.5%), and high pain tolerance (79.5%) were some of the prominent features. Patients with MEF2C variants were similarly affected as those with deletions. Female subjects showed higher verbal abilities. Conclusion: This is the largest natural history study to date and establishes a comprehensive review of developmental and clinical features for MEF2C-related disorders. This data can help providers diagnose patients and form the basis for longitudinal or genotype-phenotype studies.