Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer Syndrome)
Joel K. Greenson, MD
Key Facts
Terminology
Germline defect in 1 or more DNA mismatch repair enzymes, which leads to neoplasia
Autosomal dominant inheritance
Clinical Issues
Most common form of heritable colon cancer
2-4% of all colon cancers in USA
Microsatellite instability testing
Immunoperoxidase stains for mismatch repair proteins
Direct sequencing of mismatch repair genes for mutations
Need test algorithm to be cost effective/sensitive/specific
Lifetime risk of CRC approximately 80%
Tumors tend to grow faster than sporadic CRCs yet have better survival
 This pedigree shows a family with Lynch syndrome and a patient  whose DNA is sequenced in the next image. Note the autosomal dominant inheritance pattern. The age of cancer onset is younger in successive generations. |
 This DNA sequencing chromatograph from the patient in the previous pedigree chart shows a frame-shift mutation  in MSH2. |
TERMINOLOGY
Abbreviations
Hereditary nonpolyposis colorectal cancer syndrome (HNPCC)
Synonyms
Lynch syndrome
Muir-Torre syndrome
Subset of HNPCC patients who also have skin tumors
Sebaceous neoplasms
Keratoacanthomas
Definitions
Germline defect in 1 or more DNA mismatch repair enzymes, which leads to neoplasia
Autosomal dominant inheritance
Mutations in MLH1, MSH2, MSH6, or PMS2 account for vast majority of cases
1st described by pathologist Aldrich Warthin in 1895
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