What is familial adenomatous polyposis (FAP)?

Updated: Jun 06, 2020
  • Author: Jaime Shalkow, MD, FACS; Chief Editor: Cameron K Tebbi, MD  more...
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Answer

Familial adenomatous polyposis (FAP) is the most common polyposis syndrome and the second most common inherited colorectal cancer syndrome. [29, 39]  It occurs in only 1 in 7000 individuals. This autosomal dominant syndrome is characterized by a mutation in the adenomatous polyposis coli (APC) gene on chromosome 5, leading to formation of numerous adenomatous polyps in the colon and rectum, beginning in the first and second decades of life. Patients with FAP have an estimated 1 in 471 risk of developing colorectal cancer before the age of 20 years, and their lifetime risk of developing the disease is nearly 100% by 40-50 years of age.

Approximately 80% of patients have a family history of FAP, while 20% appear to be de novo mutations. [40]  

The APC tumor-suppressor gene encodes a large multifunctional protein product that is involved in a broad spectrum of cellular processes, such as cell cycle regulation, apoptosis, cell adhesion and migration, microtubule assembly, cell fate determination, and chromosomal stability. The main function of APC is to downregulate β-catenin, which inhibits the Wnt signaling pathway. The gene's loss of function leads to increased cellular proliferation.

FAP has classic and attenuated forms. In classic FAP, hundreds to thousands of adenomatous polyps tend to concentrate in the distal colon and rectum. Attenuated FAP is characterized by fewer (10-100) polyps, which tend to be located in the proximal large intestine. Age of onset is later than that of classic FAP, with malignant transformation also occurring 10 to 20 years later.

Cancer occurs only rarely in patients with FAP who are younger than 20 years; however, these cases are usually associated with a severe polyposis phenotype.

Extracolonic manifestations of FAP include congenital hypertrophy of the retinal pigmented epithelium; gastric and duodenal polyps; desmoid tumors and skin lesions, including fibromas, lipomas, and sebaceous cysts; dental anomalies; and osteomas of the jaw and skull. [39]

Prophylactic colectomy is the operation of choice for the management of FAP, although recommendations on the timing or age of colectomy remain unclear. Patients with classic FAP usually undergo surgery between 15 and 25 years of age. [39]  

Surgical choices include the following:

  • Total proctocolectomy with ileal pouch anal anastomosis (IPAA)
  • Total abdominal colectomy with ileorectal anastomosis (IRA)
  • Proctocolectomy with ileostomy

Total proctocolectomy with IPAA is an adequate restorative procedure, which effectively minimizes the risk of colorectal cancer while maintaining continence. Abdominal colectomy with IRA has also been used; however, 30% of patients who undergo this procedure will develop rectal cancer by age 60 years. [40]

A 1-stage IPAA results in better long-term bowel control but is also associated with an increased incidence of anastomotic leakage, reoperation, and polyp recurrence and should, therefore, be reserved for selected patients. A 2-stage IPAA with diverting ileostomy seems to minimize anastomotic leaks. [39]

For colonic resection, a combination of oral and mechanical bowel preparation is associated with fewer operative complications, including anastomosis leakage, as well as superficial and intra-abdominal infections. [41]


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