RFC1 and congenital heart disease: In addition, maternal RFC-1 genetic polymorphisms known to be in linkage disequilibrium with the 80A>G one have been associated with an increased risk for congenital heart defects in the DS offspring [32], overall indicating a possible contribution of maternal variants in this gene in modulating both the risk for chromosome 21 malsegregation as well as the onset of DS-associated diseases in the offspring.