Polymorphisms in congenital heart disease and extracardiac disorders.

Congenital heart disease (CHD) is associated with long-term complications and frequently occurs alongside extracardiac disorders. CHD is strongly associated with structural variants, but genetic polymorphisms, although less frequently discussed, also play an important role. This review aims to explore the role of polymorphisms in CHD and to examine the association between CHD and extracardiac disorders. Polymorphisms implicated in CHD have been identified in genes related to matricellular proteins, angiogenesis and vasculogenesis, folic acid metabolism, transcription factors, and epigenetic regulators, including DNA methylation and non-coding RNAs. Notably, polymorphisms associated with CHD have also been linked to a range of extracardiac disorders, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), type 1 diabetes (T1D), asthma, Wilms tumor, vitiligo, neural tube defects, non-syndromic cleft lip and palate, and retinopathy of prematurity (ROP). Early identification of these polymorphisms through prenatal testing may allow timely preventive interventions to reduce the risk of CHD and related extracardiac disorders.