Careful genetic mapping along with clinical studies during the last several years have attracted attention to a strong relationship between folate metabolism and DS: (i) out of >500 Hsa21 genes triplicated in DS, several genes including reduced folate carrier (RFC1 or SLC19A1) and Cystathionine β-synthase (CBS) have been linked to folate metabolism (Gardiner, 2015); (ii) Hsa21 has a high frequency of regions with altered methylation; and (iii) failure in folate metabolism leads to learning disability in humans. This evidence concerns the gene SLC19A1 and Dravet syndrome.