The common R653Q variant (MTHFD1 c.1958 G > A; rs2236225, ~20% QQ in European populations) compromises the synthetase activity of MTHFD1 [4] and has been identified as a risk factor for neural tube defects (NTD), heart defects, intrauterine growth restriction, and pregnancy loss [4,5,6,7]. This evidence concerns the gene MTHFD1 and isolated spina bifida.