Despite that a direct evidence of a link between folate pathway gene polymorphisms and DNA methylation levels of chromosome 21 peri-centromeric regions has not yet been demonstrated, two recent genetic association studies suggest that promoter polymorphisms of the DNMT3B gene might be associated with the maternal risk of birth of a child with DS (Coppedè et al., 2013b; Jaiswal et al., 2015). The gene discussed is DNMT3B; the disease is Dravet syndrome.