Familial adenomatous polyposis

With 160,000 new cases diagnosed each year, colorectal carcinoma is the third most common malignancy in the United States. Twenty percent of all cases are secondary to an inherited genetic trait. Familial adenomatous polyposis (FAP) accounts for 1% of all colorectal cancers. Germline mutations in the adenomatous polyposis coli gene, mapped to chromosome 5q21, have been linked to this inherited form of colorectal cancer. Over 400 different mutations have been identified. Phenotypic expression of the disease is variable, ranging from an early-onset aggressive form to a late-onset attenuated variant. FAP has three notable forms. Gardner's syndrome is FAP associated with multiple soft tissue and bony abnormalities, ocular lesions, and upper gastrointestinal (GI) polyposis. Turcot's syndrome is adenomatous polyposis associated with central nervous system tumors. Attenuated FAP is a late onset disease (after 50 years of age). Patients with attenuated FAP have fewer polyps (fewer than 100) that are more proximal in location. Individuals diagnosed with FAP have a 100% lifetime risk of developing colorectal cancer. Moreover, they are at risk for duodenal and periampullary adenocarcinoma as well as desmoid tumors. Successful treatment of these patients depends upon early diagnosis. Therapeutic options include prophylactic colectomy with ileorectal anastomosis, total proctocolectomy with ileal pouch anal anastomosis reconstruction, or end ileostomy. Surveillance of the upper GI tract is necessary to evaluate for duodenal adenomatosis. Progressive adenomatosis, severe dysplasia in a polyp, or duodenal/periampullary adenocarcinoma are indications for surgical intervention. The development of polyposis registries, genetic testing, genetic counseling, and early screening colonoscopy are essential to early diagnosis and successful management of this disease.