Familial adenomatous polyposis syndromes

Familial adenomatous polyposis (FAP) syndrome is a hereditary colorectal cancer syndrome 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 gene.

In the absence of total colectomy or endoscopic polyp clearance, colorectal cancer arises in close to 100% of patients with FAP by 40 years of age and in 80% of patients with attenuated FAP by 60 years of age.

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 patients with FAP/attenuated FAP 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 the age of 40 years 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

Individuals with FAP also have an increased lifetime risk for other cancers, including duodenal/ampullary cancer (1% to 10%), thyroid cancer (1% to 12%), gastric cancer (0.1% to 7.1%), and hepatoblastoma (0.4% to 2.5%, usually by age 5 years).[3]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: colorectal [internet publication]. https://www.nccn.org/guidelines/category_1 ​ FAP features that occur outside of the gastrointestinal tract include skin cysts, lipomas and fibromas, supernumerary teeth, thyroid nodules, 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.[4]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.