Familial adenomatous polyposis

An inherited disease characterized by the development of colorectal polyps and an increased predisposition to develop colorectal cancer. It may be caused by the presence of pathogenic variants in the APC and MUTYH genes.

Familial adenomatous polyposis (FAP) is a pathology characterised by the appearance, in the second decade of life, of hundreds or thousands of adenomatous polyps in the rectum and colon area that, if left untreated, can lead to colorectal cancer (CRC).

Classic FAP is inherited in an autosomal dominant manner and results from a copy of a pathogenic variant in the APC gene. In some cases, it may be due to alterations in another gene, called MUTYH, causing recessively transmitted polyposis, which is characterised by a slightly increased risk of developing CRC and by the presence of polyps/adenomas in the upper and lower gastrointestinal tract.

FAP has an incidence of 1 case per 8,300 people, affects both sexes equally, and accounts for less than 1% of CRC cases. The prevalence in the European Union is estimated at 1 case per 11,300-37,600 inhabitants.

Symptoms

Most patients are asymptomatic for years until the adenomas are large and numerous, causing rectal bleeding or even anemia. Generally, cancer begins to develop 15-20 years after the appearance of the polyps. Nonspecific symptoms include constipation or diarrhea, abdominal pain, palpable abdominal masses, and weight loss. FAP may present with some extraintestinal manifestations: osteomas or benign cancers, dental anomalies, congenital hypertrophy of the retinal pigment epithelium, desmoid tumors or benign cancers in connective tissues, and extracolonic cancers.

There is a less aggressive variant, attenuated FAP, which is characterized by a lower number of pólipids (typically between 10 and 100), appearance of adenomas at a later age, and a lower risk of cancer.

Disease management

The main goals of FAP management are CRC prevention and a good quality of life. Patients with classic FAP associated with PCa have a nearly 100% risk of developing CRC, although this risk is markedly reduced when they enter a screening program and are treated. Therefore, prophylactic colorectal surgery is usually performed at an early age and is followed up with lifelong follow-up with perioperative endoscopies. Revisions are necessary as adenomas arise and grow in the retained rectum or ileal pouch.

Current CRC risk surveillance measures in patients with MUTYH-associated FAP include a high-quality colonoscopy every 1-2 years, beginning no later than age 25-30 years.

Genes analyzed

APC MUTYH

Bibliography

Aelvoet AS, Buttitta F, Ricciardiello L, et al. Management of familial adenomatous polyposis and MUTYH-associated polyposis; new insights. Best Pract Res Clin Gastroenterol. 2022 Jun-Aug;58-59:101793.

MUTYH-associated polyposis.

Leoz ML, Carballal S, Moreira L, et al. The genetic basis of familial adenomatous polyposis and its implications for clinical practice and risk management. Appl Clin Genet. 2015 Apr 16;8:95-107.

Nielsen M, Joerink-van de Beld MC, Jones N, et al. Analysis of MUTYH genotypes and colorectal phenotypes in patients With MUTYH-associated polyposis. Gastroenterology. 2009 Feb;136(2):471-6.

Yen T, Stanich PP, Axell L, Patel SG. APC-Associated Polyposis Conditions. 1998 Dec 18 [updated 2022 May 12]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023.

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