Afterward, the association of MMA with several heritable conditions (i.e., Down syndrome, sickle cell disease, neurofibromatosis type 1), the high familial rate, and the strong linkage between the disease and variants of Ring Finger Protein 213 (RNF213) gene in East Asian patients strengthened the role of genetic factors in MMA pathogenesis [16,17,18]. This evidence concerns the gene RNF213 and Down syndrome.