Attenuated familial adenomatous polyposis (AFAP) a phenotypically and genotypically distinctive variant of FAP

Henry T. Lynch, Thomas Smyrk, Thomas McGinn, Stephen Lanspa, Jennifer Cavalieri, Jane Lynch, Susan Slominski‐Castor, Matthew C. Cayouette, Ira Priluck, Michael C. Luce

Research output: Contribution to journalArticlepeer-review

222 Scopus citations


Background. The usual manifestation of familial adenomatous polyposis (FAP) is hundreds or thousands of colonic adenomas. The authors previously described a colon cancer‐prone syndrome characterized by fewer adenomas (1–100), most located in the proximal colon, and upper gastrointestinal lesions, particularly fundic gland polyps and duodenal adenomas. The colonic adenomas are often flat rather than polypoid, a feature emphasized in earlier reports with the term “hereditary flat adenoma syndrome.” The syndrome has an autosomal dominant pattern of inheritance and is linked to the adenomatous polyposis coli [APC] locus at 5q. Methods. This is a descriptive study based on one family that was followed for more than a decade. Total cell RNA was isolated from cultured lymphoblasts, and an in vitro protein synthesis assay was used to detect APC mutations. Sixteen individuals whose APC mutation status was known had sequential endoscopic evaluations. Five patients were given one or more courses of sulindac. Results. There was perfect concordance between clinical affected status and an APC mutation. All affected members generated a 16‐kDa polypeptide from the mutant allele, consistent with a 2‐base pair deletion at the extreme 5′end of the APC gene. Sixteen mutation‐positive individuals underwent upper gastrointestinal endoscopy and colonoscopy; 13 had colonic adenomas, with the number visualized at any one examination ranging from 1 to greater than 50. Upper gastrointestinal examination revealed fundic gland polyps in 15, gastric or duodenal adenomas in 4, and periampullary carcinoma in 1. Conclusion. AFAP is a phenotypically distinctive syndrome, differing from classic FAP by having fewer colonic adenomas that tend to be proximally distributed and flat rather than polypoid. The position of the APC germline mutation appears to allow for the molecular differentiation between FAP and the attenuated variant in that the extreme 5′ APC mutations are associated with the latter.

Original languageEnglish (US)
Pages (from-to)2427-2433
Number of pages7
Issue number12
StatePublished - Dec 15 1995


  • APC gene
  • colon cancer
  • genetics
  • hereditary flat adenoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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