Unlike Lynch syndrome that is caused by germ-line mutations of MMR genes, such as MutL homolog 1 (MLH1) (32% of cases), MutS homolog 2 (MSH2) (39%), postmeiotic segregation increased 2 (PMS2) (15%), and MSH6 (14%) [18], MMR deficiency in sporadic CRCs is due mainly to silencing of the MMR genes, mostly MLH1 (>80% of cases), by promoter hypermethylation [19, 20]. This evidence concerns the gene MRC1 and hyperinsulinemic hypoglycemia, familial, 4.