MTHFR and coronary artery disorder: What is missing is an updated systematic review and meta-analysis of the studies investigating MTHFR C677T and/or A1298C polymorphisms as maternal risk factors for DS addressing not only the overall contribution of each of the two polymorphisms to DS risk, but performed in such a way to extract data on combined genotypes, ethnicity, serum folate levels, maternal age at conception, errors occurred at maternal meiosis I or II, as well as data on CHD in the DS children, in order to shed light on the different role of the MTHFR genotype in the various subgroups.