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Up to 4% of all colorectal cancers are caused by germline genetic mutations that impose on carriers a high lifetime risk of developing colorectal cancer (see Chapter 39). Because the diagnosis of these disorders has important implications for treatment of affected patients and for screening of family members, it is important to consider these disorders in patients with a family history of colorectal cancer that has affected more than one family member, those with a personal or family history of colorectal cancer developing at an early age (50 years or younger), those with a personal or family history of multiple polyps (more than 10), and those with a personal or family history of multiple extracolonic malignancies.



  • Inherited condition characterized by early development of hundreds to thousands of colonic adenomatous polyps.

  • Variety of extracolonic manifestations (eg, duodenal adenomas, desmoid tumors, and osteomas) and extracolonic cancers (stomach, duodenum, thyroid).

  • Attenuated variant with < 100 (average 25) colonic adenomas.

  • Genetic testing confirms mutation of APC gene (90%) or MUTYH gene (8%).

  • Prophylactic colectomy recommended to prevent otherwise inevitable colorectal cancer (adenocarcinoma).

General Considerations

Familial adenomatous polyposis (FAP) is a syndrome affecting 1:10,000 people and accounts for approximately 0.5% of colorectal cancers. The classic form of FAP is characterized by the development of hundreds to thousands of colonic adenomatous polyps and a variety of extracolonic manifestations. Of patients with classic FAP, approximately 90% have a mutation in the APC gene that is inherited in an autosomal dominant fashion and 8% have mutations in the MUTYH gene that are inherited in an autosomal recessive fashion. FAP arises de novo in 25% of patients in the absence of genetic mutations in the parents. An attenuated variant of FAP also has been recognized in which an average of only 25 polyps (range of 1–100) develop.

Clinical Findings

A. Symptoms and Signs

In classic FAP, colorectal polyps develop by a mean age of 15 years and cancer often by age 40 years. Unless prophylactic colectomy is performed, colorectal cancer is inevitable by age 50 years. In attenuated FAP, the mean age for development of cancer is about 56 years.

Adenomatous polyps of the duodenum and periampullary area develop in over 90% of patients, resulting in a 5–8% lifetime risk of adenocarcinoma. Adenomas occur less frequently in the gastric antrum and small bowel and, in those locations, have a lower risk of malignant transformation. Gastric fundus gland polyps occur in over 50% but have an extremely low (0.6%) malignant potential.

A variety of other benign extraintestinal manifestations, including soft tissue tumors of the skin, desmoid tumors, osteomas, and congenital hypertrophy of the retinal pigment, develop in some patients with FAP. These extraintestinal manifestations vary among families, depending in part on the type or site ...

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