Familial adenomatous polyposis

Familial adenomatous polyposis (FAP), also known as adenomatous polyposis coli (APC), is an inherited colorectal cancer predisposition syndrome characterized by the development of hundreds to thousands of adenomatous polyps throughout the colon and rectum, typically beginning in adolescence. FAP is caused by germline mutations in the APC tumor suppressor gene located on chromosome 5q21. Without intervention, virtually all affected individuals will develop colorectal cancer, usually by the age of 40. An attenuated form of the disease (attenuated FAP or AFAP) exists, in which fewer polyps develop (typically 10–100), with a later age of onset and a somewhat lower but still significantly elevated cancer risk. Beyond the gastrointestinal tract, FAP can affect multiple organ systems. Extracolonic manifestations include upper gastrointestinal polyps (particularly duodenal and gastric fundic gland polyps), desmoid tumors (benign but locally aggressive fibrous growths often occurring in the abdomen or abdominal wall), osteomas of the jaw and skull, dental abnormalities, congenital hypertrophy of the retinal pigment epithelium (CHRPE), epidermoid cysts, and thyroid tumors (particularly papillary thyroid carcinoma). When FAP is accompanied by osteomas, soft tissue tumors, and other extracolonic features, it has historically been referred to as Gardner syndrome. Hepatoblastoma, though rare, can occur in young children with FAP. Management of FAP centers on early detection through genetic testing and endoscopic surveillance, typically beginning in the early teenage years for individuals at risk. Prophylactic colectomy — surgical removal of the colon — is the standard of care to prevent colorectal cancer and is usually recommended in late adolescence or early adulthood. Options include total proctocolectomy with ileal pouch-anal anastomosis or subtotal colectomy with ileorectal anastomosis, depending on the extent of rectal involvement. Lifelong surveillance of the upper gastrointestinal tract, thyroid, and remaining rectal tissue (if preserved) is essential. Pharmacological agents such as sulindac and celecoxib have been studied as adjuncts to reduce polyp burden but are not substitutes for surgery. Genetic counseling is strongly recommended for affected families.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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