Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of hereditary colon cancer

World J Gastroenterol. 2015 Aug 21;21(31):9253-61. doi: 10.3748/wjg.v21.i31.9253.


Hereditary non-polyposis colorectal cancer (HNPCC) was previously synonymous with Lynch syndrome; however, identification of the role of germline mutations in the DNA mismatch repair (MMR) genes has made it possible to differentiate Lynch syndrome from other conditions associated with familial colorectal cancer (CRC). Broadly, HNPCC may be dichotomized into conditions that demonstrate defective DNA MMR and microsatellite instability (MSI) vs those conditions that demonstrate intact DNA MMR. Conditions characterized by MMR deficient CRCs include Lynch syndrome (germline MMR mutation), Lynch-like syndrome (biallelic somatic MMR mutations), constitutional MMR deficiency syndrome (biallelic germline MMR mutations), and sporadic MSI CRC (somatic biallelic methylation of MLH1). HNPCC conditions with intact DNA MMR associated with familial CRC include polymerase proofreading associated polyposis and familial colorectal cancer type X. Although next generation sequencing technologies have elucidated the genetic cause for some HNPCC conditions, others remain genetically undefined. Differentiating between Lynch syndrome and the other HNPCC disorders has profound implications for cancer risk assessment and surveillance of affected patients and their at-risk relatives. Clinical suspicion coupled with molecular tumor analysis and testing for germline mutations can help differentiate the clinical mimicry within HNPCC and facilitate diagnosis and management.

Keywords: Constitutional mismatch repair deficiency syndrome; DNA mismatch repair; Familial colorectal cancer; Familial colorectal cancer type X; Hereditary colorectal cancer; Hereditary non-polyposis colorectal cancer; Lynch syndrome; Lynch-like syndrome; Microsatellite instability.

Publication types

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

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Brain Neoplasms / genetics
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms, Hereditary Nonpolyposis / diagnosis
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • DNA Mismatch Repair*
  • DNA Mutational Analysis
  • Diagnosis, Differential
  • Genetic Predisposition to Disease
  • Heredity
  • Humans
  • Microsatellite Instability*
  • Mutation*
  • Neoplastic Syndromes, Hereditary / genetics
  • Pedigree
  • Phenotype
  • Predictive Value of Tests


  • Biomarkers, Tumor

Supplementary concepts

  • Turcot syndrome