To the best of our knowledge, this is the first study to investigate the impact of endogenous maternal factors (MTHFR C677T polymorphism and maternal age) and exogenous maternal factors (cigarette smoking, alcohol intake, medication use, body mass index, dietary habits such as folate intake) on LINE-1 methylation in the mothers of children with DS regarding the presence of DS-associated CHDs, particularly regarding the presence of septal defect. This evidence concerns the gene MTHFR and Dravet syndrome.