Lynch syndrome

Abstract

Lynch syndrome is a highly penetrant hereditary cancer syndrome caused by pathogenic germline variants in DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, PMS2, and EPCAM. Historically identified on the basis of family history of colorectal and endometrial cancers exhibiting autosomal dominant inheritance, universal screening of CRCs and endometrial cancers for features of MMR deficiency, together with cascade genetic testing in families, is at present the most effective approach for identifying individuals with Lynch syndrome. Here we review the history of Lynch syndrome, as well as the clinical and molecular investigations that have contributed to our understanding of Lynch syndrome and informed current approaches to diagnosis and clinical management.