The estimated lifetime risks associated with endometrial cancer (EC) and ovarian cancer (OC) are as high as 48.9% and 17.4%, respectively, and EC is often a sentinel cancer that identifies new LS families.3,4 While pathogenic variants in the mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2 and deletions in the EPCAM gene, which epigenetically silences MSH2, cause LS, recent data support variable cancer risks based on the altered MMR gene.3,4. This evidence concerns the gene MSH2 and Leigh syndrome.