MGA-related syndrome: A proposed novel disorder

Abstract

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.

Keywords: MGA; candidate gene; clinical exome sequencing; congenital anomalies; congenital heart defect; craniofacial dysmorphism; gene discovery; genetic testing; hearing loss; neurodevelopmental disorder.

Figure 1

Individual 3, a 2-year-old female Note a high forehead, frontal bossing, hypertelorism, depressed and wide nasal bridge and thin upper lip. She also had craniosynostosis, hypotonia, and developmental delays.

Figure 2

Venn diagram showing the shared and unique phenotypic categories of individuals 1, 2, and 3 Common features shared between all three individuals include neurodevelopmental delay, facial and eye anomalies, and musculoskeletal, genitourinary, and cardiovascular anomalies.