In females with LS, gynecological cancer risk has been proven to equal or exceed the risk of CRC and it can be the sentinel malignancy in up to 35–40% of cases, with cumulative incidences at 75 years of age of EC and OC of 37% and 11% for MLH1, 48.9 and 17.4% for MSH2, 41.1 and 10.8% for MSH6 and 12.8 and 3% for PMS2, respectively [2,3]. Here, MSH6 is linked to Leigh syndrome.