In hereditary CRC syndromes, adenomatous polyposis syndrome accounts for ~1% and is strongly associated with APC (dominant inheritance) and MUTYH (recessive inheritance); Lynch syndrome (LS) accounts for 2–3% and is associated with germline or epistatic mutations in the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2; hamartomatous polyposis syndrome (<0.1%) is caused by mutations in SMAD4, BMPR1A, STK11, and PTEN. The gene discussed is MSH6; the disease is Leigh syndrome.