Familial Adenomatous Polyposis (FAP) and Other Polyposis Syndromes

Abstract

The number of adenomas allows the clinical differentiation of familial adenomatous polyposis into the classical (FAP), attenuated (AFAP), and atypical (ATFAP) forms. Mutations in the APC gene are found in 80% of FAP patients, with inheritance being autosomal dominant. Mutations in MUTYH (MUTYH-associated polyposis, or MAP) follow a recessive inheritance and clinically dominate AFAP. MAP is associated with adenomas, but hyperplastic polyps and serrated adenomas can also be prevalent. Extraintestinal manifestations are associated with FAP. The recurrence risk for FAP is 50% and is below 1% for MAP. Hyperplastic polyposis syndromes (HPS) can show a familial occurrence; mutation analysis of the polyp tissue allows preliminary subdivision into cases with mutations of either BRAF or KRAS and cases with no mutation in either of these genes. The genetic predisposition of HPS in the germline is thus far unknown. The genetics of juvenile polyposis has been established; hamartomatous polyposis syndromes (Peutz-Jeghers and Cowden syndromes) show a 50% mutation detection rate. Especially in hamartomatous polyposis syndromes, the risk for extraintestinal cancers needs to be considered. (copyright) 2009 Springer Medizin Verlag.