MLH1 and Leigh syndrome: In patients with LS, colorectal and endometrial cancers are the most common “sentinel cancers” with which patients present to clinical attention.7, 11, 16, 17, 18, 19 The most common and clinically relevant mutations in LS occur in the MLH1, MSH2, MSH6, PMS2, and EPCAM genes.20, 21 A report from the prospective LS database followed over 3000 patients for a total of 24 475 person years and determined the cumulative incidences of EC (at age 75) to be 43%, 57%, and 46%, for patients with mutations in MLH1, MSH2, and MSH6, respectively.2