Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications

Clin Genet. 2009 Jul;76(1):1-18. doi: 10.1111/j.1399-0004.2009.01230.x.


More than one million patients will manifest colorectal cancer (CRC) this year of which, conservatively, approximately 3% (approximately 30,700 cases) will have Lynch syndrome (LS), the most common hereditary CRC predisposing syndrome. Each case belongs to a family with clinical needs that require genetic counseling, DNA testing for mismatch repair genes (most frequently MLH1 or MSH2) and screening for CRC. Colonoscopy is mandated, given CRC's proximal occurrence (70-80% proximal to the splenic flexure). Due to its early age of onset (average 45 years of age), colonoscopy needs to start by age 25, and because of its accelerated carcinogenesis, it should be repeated every 1 to 2 years through age 40 and then annually thereafter. Should CRC occur, subtotal colectomy may be necessary, given the marked frequency of synchronous and metachronous CRC. Because 40-60% of female patients will manifest endometrial cancer, tailored management is essential. Additional extracolonic cancers include ovary, stomach, small bowel, pancreas, hepatobiliary tract, upper uroepithelial tract, brain (Turcot variant) and sebaceous adenomas/carcinomas (Muir-Torre variant). LS explains only 10-25% of familial CRC.

Publication types

  • Historical Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Colorectal Neoplasms, Hereditary Nonpolyposis / diagnosis
  • Colorectal Neoplasms, Hereditary Nonpolyposis / drug therapy
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / history*
  • Genetic Counseling
  • Genetic Privacy / legislation & jurisprudence
  • History, 19th Century
  • History, 20th Century
  • Humans
  • Informed Consent
  • Mass Screening*