Among hereditary CRC syndromes, LS accounts for approximately 3% of all cases and is caused by a germline mutation in one allele of the DNA mismatch repair (MMR) genes, such as MLH1, MSH2, MSH6, or PMS2. Microsatellite instability (MSI) is a hypermutable phenotype linked to LS caused by the loss of DNA mismatch repair activity and it is also present in 15% of sporadic CRCs [6,8,21,22,23]. Here, MLH1 is linked to Leigh syndrome.