Comprehensive investigation of the phenotype of MEF2C‐related disorders in human patients: A systematic review

Abstract MEF2C ‐related disorders (aka MEF2C ‐haploinsufficiency) are caused by variations in or involving the MEF2C gene and are characterized by intellectual disability, developmental delay, lack of speech, limited walking, and seizures. Despite these findings, the disorder is not easily recognized clinically. We performed a systematic review following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines to assemble the most comprehensive list of patients and their phenotypes. Through searching PubMed, Web of Science, and MEDLINE, 43 articles met the inclusion criteria and were fully reviewed. One hundred and seventeen patients were identified from these publications with most having a phenotype of intellectual disability, developmental delay, seizures, hypotonia, absent speech, inability to walk, stereotypic movements, and MRI abnormalities. Nonclassical findings included one patient with a question mark ear, two patients with a jugular pit, one patient with a unique neuroendocrine finding, and nine patients that did not have MEF2C deletions or disruptions but may be affected due to a positional effect on MEF2C . This systematic review characterizes the phenotype of MEF2C ‐related disorders, documents the severity of this condition, and will help providers to better diagnose and care for patients and their families. Additionally, this compiled information provides a comprehensive resource for investigators interested in pursuing specific genotype–phenotype correlations.