MUTYH-Associated Polyposis (MAP)
(based on Dutch Guideline 2017)

Diagnostic criteria:

  • Detection of bi-allelic mutations in the MUTYH-gene


  • Autosomal recessive


  • General population:
  • Heterozygous MUTYH –mutation carriers: 2%
  • Bi-allelic mutation carriers: ~ 1: 10.000

Clinical features:

  • Usually 10 to a few hundreds of adenomatous polyps in the colon and rectum
  • Adenomatous polyps occur at a mean age of 48 years (range 20-60 years)
  • Possible accelerated progression from adenoma to CRC
  • 60% of MAP-patients has CRC at the time of diagnosis
  • Risk of colorectal cancer 60-70%
  • 64% of MAP-associated CRC has a specific KRAS mutation (c.34G> T in codon 12)
  • Tumor spectrum outside the colon: duodenal adenomas (17%) and duodenal carcinoma (4%); slightly increased risk ovarian, endometrial, breast, bladder and skin cancer and sebaceous gland adenomas

Genetic basis:

  • Mutation in both alleles of the gene MUTYH

DNA diagnostics:
Detection of bi-allelic mutations:

  • 5-10% of patients with adenomas 10-100
  • 4% of unselected CRC patients
  • 5% of patients with CRC <50 years

Indication for referral to a clinical geneticist for counseling and DNA diagnostics:

  • New patients and families if they meet one of the following criteria:
  • FAP without proven APC mutation
  • Cumulative ≥10 adenomas with or without CRC in patients <60 years
  • Cumulative> 20 adenomas with or without CRC in patients <70 years
  • Less than 10 adenomas in young patients if that number is remarkably high for their age
  • For family members of index patient
  • Siblings: 25% risk of bi-allelic mutation
  • Partner: MUTYH-analysis to assess risk of biallelic mutation in children

Periodic examination:
For carriers of bi-allelic mutations MUTYH

  • Colonoscopy 1x / 2 years from 18 years (same as AFAP recommendations), the interval depends of the number of adenomas
  • Gastroduodenoscopy: 1x / 5 years from 25-30 years, frequency depending on findings (Spigelman score)

Heterozygous mutation carriers have a 1 to 2x increased risk of CRC; no indication of periodic examination


  • The treatment is similar to the treatment of AFAP patients
  • In patients with only a few polyps, colonoscopy and polypectomy are recommended
  • Colectomy is indicated in patients in whom the number and the size of the polyps do not allow adequate surveillance
  • In most patients, a subtotal colectomy (IRA) a good option



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  3. Nielsen M, Franks PF Reinards THCM et al. Multiplicity in polyp count and extra-colonic manifestations in 40 Dutch MYH associated polyposis coli (MAP) patients. J Med Genet 2005; 42: e54
  4. Nielsen M, Joerink-the Called M, N Jones et al. Analysis of MUTYH genotypes and phenotypes with colorectal MUTYH-associated polyposis. Gastroenterology 2009; 136: 471-6
  5. Jones N, S Vogt, Nielsen M et al. Increased colorectal cancer incidence in obligate carriers or heterozygous mutations in MUTYH. Gastroenterology 2009; 137: 489-94
  6. Vogt S, N Jones, Christian D et al. Expanded extracolonic tumor spectrum MUTYH-associated polyposis. Gastroenterology 2009; 137: 1976-85. e1-10
  7. Nieuwenhuis MH, Vogt S, Jones N, et al. Evidence for accelerated adenoma– colorectal carcinoma progression in MUTYH-associated polyposis? Gut 2012; 61: 734-8
  8. Win AK, Dowty JG Cleary SP et al. Risk of colorectal cancer for carriers of mutations in MUTYH, with and without a family history of cancer. Gastroenterology 2014; 146: 1208-11.e1-