Molecular genetics of congenital heart disease

Congenital heart disease (CHD) is the most prevalent human birth defect and remains a leading cause of mortality in childhood. Although advancements in surgical and medical interventions have significantly reduced mortality rates among infants with critical CHDs, many survivors experience substantial cardiac and extracardiac comorbidities that affect their quality of life. The etiology of CHD is multifactorial, involving both genetic and environmental factors, yet a definitive cause remains unidentified in many cases. Recent advancements in genetic testing technologies have improved our ability to identify the genetic causes of CHD. This review presents an updated summary of the established genetic contributions to CHD, including chromosomal aberrations and mutations in genes associated with transcription factors, cardiac structural proteins, chromatin modifiers, cilia-related proteins, and cell signaling pathways. Furthermore, we discuss recent findings that support the roles of non-coding mutations and complex inheritance in the etiology of CHD.