Familial adenomatous polyposis syndromes

Hereditary colorectal cancer syndromes characterized by the development of hundreds to thousands of colorectal adenomas. The attenuated form leads to the formation of fewer than 100 polyps.

Caused by germline mutations of the adenomatous polyposis coli (APC) gene.

Colorectal cancer arises in close to 100% of patients with familial adenomatous polyposis (FAP) by 40 years of age and in 80% of attenuated FAP patients by 60 years of age in the absence of either total colectomy or endoscopic polyp clearance.

Prophylactic proctocolectomy is the main means for preventing colorectal cancer in FAP.

Duodenal and periampullary polyps lead to an increased risk for duodenal cancer, which is the most common cause of cancer death in FAP/attenuated FAP patients who have had prophylactic colectomy.

Familial adenomatous polyposis (FAP) syndrome is an autosomal-dominant condition caused by germline adenomatous polyposis coli (APC) gene mutations. Patients with classical FAP have hundreds to thousands of colorectal adenomas and a nearly 100% risk for colorectal cancer by age 40 if prophylactic colectomy is not performed. Attenuated FAP is also caused by APC mutations and is characterized by fewer than 100 adenomas and a later age of colorectal cancer onset.[1]Bjork J, Akerbrant H, Iselius L, et al. Epidemiology of familial adenomatous polyposis in Sweden: changes over time and differences in phenotype between males and females. Scand J Gastroenterol. 1999;34:1230-1235. http://www.ncbi.nlm.nih.gov/pubmed/10636071?tool=bestpractice.com [2]Knudsen AL, Bisgaard ML, Bulow S. Attenuated familial adenomatous polyposis (AFAP): a review of the literature. Fam Cancer. 2003;2:43-55. http://www.ncbi.nlm.nih.gov/pubmed/14574166?tool=bestpractice.com

FAP features that occur outside of the gastrointestinal tract include skin cysts, lipomas and fibromas, supernumerary teeth, thyroid nodules and cancer, osteomas, desmoid tumors, adrenal adenomas, and congenital hypertrophy of the retinal pigment epithelium. Previously, patients with FAP and extraintestinal features were diagnosed with Gardner syndrome and patients with FAP and medulloblastomas were said to have Turcot syndrome.[3]Syngal S, Brand RE, Church JM, et al.; American College of Gastroenterology. ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015 Feb;110(2):223-62. http://www.ncbi.nlm.nih.gov/pubmed/25645574?tool=bestpractice.com  Use of the terms Gardner syndrome and Turcot syndrome are historical and should be avoided as they are FAP spectrum phenotypes and are part of APC-associated polyposis. Patients may also find these terms confusing.