MGA-related syndrome: A proposed novel disorder

MGA (OMIM: 616061) encodes a dual-specificity transcription factor that regulates the expression of Max-network and T-box family target genes, important in embryogenesis. Previous studies have linked MGA to various phenotypes, including neurodevelopmental disorders, congenital heart disease, and early-onset Parkinson’s disease. Here, we describe the clinical phenotype of individuals with de novo, heterozygous predicted loss-of-function variants in MGA, suggesting a unique disorder involving both neurodevelopmental and congenital anomalies. In addition to developmental delays, certain congenital anomalies were present in all individuals in this cohort including cardiac anomalies, male genital malformations, and craniofacial dysmorphisms. Additional findings seen in multiple individuals in this cohort include hypotonia, abnormal brain imaging, hearing loss, sleep dysfunction, urinary issues, skeletal abnormalities, and feeding difficulties. These findings provide support for MGA as a gene intolerant to protein truncation with a broad phenotypic spectrum. MGA encodes a dual-specificity transcription factor important in embryogenesis. We describe the clinical phenotype of individuals with predicted loss-of-function variants. Developmental delays, musculoskeletal, cardiovascular, genitourinary, and craniofacial anomalies were observed. Candidate gene MGA may be intolerant to protein truncating variation with a broad phenotypic spectrum including neurodevelopmental and congenital anomalies.