Familial adenomatous polyposis

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Familial adenomatous polyposis


Familial adenomatous polyposis is an inherited condition that typically presents with extensive adenomatous polyps of the colon. These polyps often develop into colorectal cancer in early adult life. Other symptoms are often present as well. These signs include polyps in the upper gastrointestinal tract, malignancies in the brain or thyroid, pigmented retinal lesions, and osteomas.


Familial adenomatous polyposis (FAP) was first clearly described as a dominantly inherited colorectal cancer susceptibility by Lockhart-Mummery in an article published in 1925. FAP has since served as a paradigm for hereditary cancer and has taught much about the diagnosis, surveillance, and management of colon cancer. It is one of the most clearly defined and well understood of the inherited colon cancer syndromes. FAP is thought to account for approximately 1% of all cases of colorectal cancer.

FAP is a disorder that is characterized by the development of hundreds to thousands of glandular colorectal tumors called adenomas or adenomatous polyps, meaning that they are benign growths made of the tissue that lines the inside of the colon. They are described as polyps because they protrude from mucous membranes. In FAP, these tumors generally develop by the second or third decade of life. They are found in the internal lining of the colon and the rectum, with a particular affinity for the left side of the colon or the rectosigmoid. By themselves, these polyps are benign but they have the ability to become malignant, leading to colorectal cancer. If the polyps are not treated properly, it is almost certain that a person affected with FAP will develop colorectal cancer by the age of 40.

Other clinical findings that may be associated with FAP include polyps in the upper gastrointestinal tract, extraintestinal manifestations such as osteomas and epidermoid cysts, desmoid formation, retinal lesions, and malignant changes in other organs. Symptoms are thought to manifest anywhere between the ages of 16 and 50 years.

FAP is also known as familial polyposis coli (FPC) and adenomatous polyposis coli (APC). Gardner syndrome and Turcot syndrome are variants of FAP. Gardner syndrome is used to describe patients with FAP and the extracolonic symptoms of osteomas, soft tissue tumors, desmoids, and dental abnormalities. Turcot syndrome is used when FAP is seen in conjunction with tumors of the central nervous system called medulloblastomas (cerebral tumors that occur in childhood). Attenuated FAP (AFAP) is another variant of FAP. In this condition, individuals present with fewer polyps, usually fewer than 100 in number and often in the right colon. Patients with AFAP may have a later onset of cancer than those with classic FAP.

Genetic profile

FAP is inherited in an autosomal dominant pattern; thus, an affected person has a 50% chance of passing the disease on to each of his or her children. It is almost 100% penetrant, meaning that nearly everyone who carries the gene mutation will show signs of the disorder. The majority of patients with FAP inherit the mutation from one of their parents. However, in approximately 25% of cases, there is no family history of the disorder and FAP occurs because of a new mutation in the affected individual.

The majority of cases of FAP are due to mutations of the APC gene, located on the long arm (or "q" arm) of chromosome 5. This gene encodes a protein that is important in cell adhesion and signal transduction. More than 300 different APC mutations have been described in FAP patients. Most APC mutations seen in individuals with FAP result in translation of a protein that is shorter than normal. This shortened protein cannot function properly.

Studies have shown that the type and location of the APC mutation seems to correlate to the clinical symptoms that a person manifests. For example, if the mutation is located near the center of the gene, colonic polyps tend to be more dense and numerous. A mutation towards the ends of the gene often leads to polyps that are fewer and more sparse, as in attenuated FAP. Additionally, mutations at one particular end (the 3= end) of the APC gene seem to be associated with a higher risk of desmoid formation. However, it is known that family members who carry identical mutations often have different clinical features. This suggests that modifying genes and/or environmental factors also influence the expression of the APC gene mutation .

The APC gene is a tumor suppressor gene, meaning that its function is to control cell growth. When APC is mutated, it does not function correctly and allows cells to grow out of control. This results in tumors that may lead to cancer. Carriers of mutations in APC inherit a germline mutation in one allele of the gene. Thus, in every one of their cells, one gene does not make the APC protein but the corresponding gene on the other chromosome continues to produce the functional protein. Thus, tumor suppression continues. However, if a somatic mutation occurs in the remaining functional gene, no APC protein is made, tumor suppression fails, and tumors develop. These somatic mutations occur in various parts of the body at various times, leading to multiple tumors forming in distinct parts of the body over a period of time. In the case of FAP, many of these tumors are confined to the colon but can occur in other organs as well.


Approximately one of 8,000 people are affected with FAP. It is seen in all racial and ethnic groups. Both sexes are affected equally.

Signs and symptoms


FAP is characterized by multiple (more than 100) adenomatous polyps of the colon and rectum. These generally develop after the first decade of life but the age of onset of adenomas is variable. Fifteen percent of individuals with FAP will show these polyps by age 10, 75% by age 20, and 90% by the age of 30. More than 95% of affected individuals will have adenomatous polyps by the age of 35. Although these polyps are benign, it is inevitable that, if left untreated, at least one of the hundreds of polyps will eventually progress to cancer. The majority of cancers appear by the age of 40 and over 90% appear by the age of 45. Symptoms of polyps and/or colorectal cancer may include rectal bleeding, change in bowel habits, iron deficiency anemia, or abdominal pain.

Upper gastrointestinal tract

Many individuals with FAP will develop adenomas in the upper gastrointestinal tract as well. The second portion of the duodenum is particularly prone to these polyps. These adenomas are benign, as they are in the colon, but about 5–8% of patients with FAP will eventually develop cancer in this area. Duodenal cancer seems to cluster in certain FAP families while being absent in others. Adenomas of other portions of the small bowel may also occur but with lesser frequency.

In people affected with FAP, benign adenomas can also be seen in the stomach. Gastric cystic fundic gland polyps are also common. These are benign polyps that occur in the fundic gland of the stomach, an organ that secretes enzymes and mucus. It is rare for these polyps to become cancerous in individuals of Western origin. However, in Japanese and Korean families with FAP, the risk of gastric cancer is reported to be increased three- to four-fold over the general population.

Ocular, skeletal, and cutaneous

Approximately two thirds of individuals with FAP will have congenital hypertrophy of the retinal pigment epithelium (CHRPE). These lesions are typically flat, oval, and pigmented. They can be detected by an ophthalmology examination. In FAP patients, these lesions are usually multiple, bilateral, or large. CHRPE does not affect vision nor does it have the potential to become malignant. However, CHRPE is a very important finding for families with a history of FAP. If CHRPE runs in a family with FAP, all or nearly all affected individuals in the family will have this finding. It can be detected at birth and can thus identify susceptible family members at a young age.

Other manifestations of FAP include dental abnormalities, such as impacted teeth, supernumerary teeth, and congenitally missing teeth. Osteomas can occur, often in the jaw area or on the forehead. Soft tissue tumors, such as lipomas, epidermoid cysts, and fibromas, are observed in some patients with FAP as well.

Other tumors and malignancies

Abdominal desmoid tumors occur in approximately 15% of individuals with FAP. Desmoids are tumors made of connective tissue. Although they are not cancerous, approximately 10% grow very aggressively and can become life threatening. They may lead to obstruction of blood vessels, the intestine, or ureters. They may also result in abdominal distention and associated pain and discomfort. Over 70% of these tumors develop in women aged 20–40 years, suggesting a hormonal role in their development. Additionally, they occur more commonly in those who have had prior abdominal surgery. Desmoids may occur as part of classical FAP, as part of Gardner syndrome, or sporadically, without the colonic findings of FAP.

Additionally, patients with FAP are at an increased risk for cancers in organs outside of the gastrointestinal tract. These include brain tumors, thyroid tumors, and hepatoblastoma. Hepatoblastoma is a malignant tumor of the liver and occurs in approximately 1.6% of patients with FAP in the first five years of life. Tumors of the adrenal cortex, biliary tract, and pancreas have also been reported.


FAP can be diagnosed clinically in any individual with greater than 100 polyps in the colon or rectum. The diagnosis is usually made via flexible sigmoidoscopy. This procedure may be done on a routine basis or to investigate possible symptoms of colon polyps and/or colorectal cancer. Flexible sigmoidoscopy involves inspecting the interior of the rectum and the sigmoid colon, or the terminal part of the colon that leads to the rectum. Once polyposis has been established, complete colonoscopy may be necessary to further evaluate the extent of the polyps. Colonoscopy is a more invasive procedure that examines the interior of the entire colon and rectum, rather than only the terminal part.

In regards to a diagnosis in someone who does not yet have colon polyps, retinoscopy, or examination of the retina, can be useful in a family where CHRPE has been associated with FAP. In these families, CHRPE is almost 100% predictive of FAP; thus, if someone shows CHRPE on an ophthalmology exam, it is very likely that he or she is affected with FAP. Although genetic testing yields more certain predictive information, retinoscopy is a relatively inexpensive and noninvasive alternative diagnostic screening measure in families with a history of FAP associated with CHRPE.

Polyps may be first detected by the passage of occult (non-visible) blood in the stool by means of fecal occult blood testing. This testing is also inexpensive and noninvasive, and if positive, could indicate that additional testing is needed.

FAP can also be diagnosed by genetic testing. This type of testing may be used to identify someone who is affected but does not yet show any symptoms of FAP. It can also confirm the diagnosis of FAP in someone who has polyposis discovered via flexible sigmoidoscopy. APC gene testing is most commonly performed by using a protein truncation test, which looks for the presence of shortened proteins caused by a mutation in the gene. This test identifies approximately 80% of those affected with FAP. The other 20% of patients likely have mutations that do not lead to a shortened protein. It is important to test an affected family member first to determine whether or not a detectable mutation is present. If a mutation is identified in this affected person, other at-risk family members can be tested for this particular mutation. However, if a mutation is not identified in the affected individual, it is likely that the mutation does not produce a shortened protein. In this case, protein truncation testing would not be informative for the rest of the family.

FAP can also be diagnosed by linkage analysis. This testing identifies approximately 95% of affected individuals, however, blood samples are required from numerous family members, including at least one affected individual. Thus, logistically, this procedure is more complicated than the protein truncation testing mentioned above.

Treatment and management

There is no treatment for FAP because the genetic abnormality cannot be fixed. Management focuses on routine surveillance of at-risk and affected individuals for early detection and treatment of colonic polyps and other manifestations.

For individuals diagnosed with FAP, either clinically or via linkage analysis or protein truncation testing, an annual sigmoidoscopy must be performed beginning around the age of 10 years. Sigmoidoscopy is preferred because it is less invasive, safer, and will generally detect the polyps in FAP, since they are numerous and located throughout the colon. Colonoscopy may be the screening tool of choice if attenuated FAP is suspected since, in this case, the adenomas are fewer in number and may be confined to the proximal region of the colon.

If polyposis is established, complete colonoscopy may be necessary to determine the extent of the polyposis and the timing of surgery. As for surgical intervention, total proctocolectomy (removal of the colon and rectum) is generally favored. In some cases, however, other options may be explored, such as total colectomy (removal of the colon only) with ileorectal anastomosis (the small intestine is attached to the upper portion of the rectum). Another option, a total colectomy with rectal mucosal protectomy and ileoanal anastomosis, involves removing the entire colon and mucosal lining of the rectum. The ileum then attaches to the anus. Fecal continence is preserved since the muscular wall and the sensory functions of the rectum are preserved.

All FAP patients require an annual medical examination with palpation of the thyroid and review of systems. Children with FAP should be screened for hepatoblastoma with liver palpation. In some cases, hepatic ultrasonography and determination of serum alpha-fetoprotein levels can be helpful as well. Upper endoscopy (visual examination of the upper GI tract) should be completed every one to four years to evaluate for gastric and duodenal polyps. Duodenal polyps that increase in size or number or show signs of becoming cancerous may require treatment. This treatment may include evaluation by computed tomography or ultrasonography. If necessary, the polyps may be removed by laser or other procedures.

For at-risk relatives of affected individuals, regular screening should begin between the ages of 10 and 12 years. This screening can be accomplished by protein truncation testing. If the test result is a true negative (i.e., negative result in a person whose affected relative had a positive result), further screening is debatable. This test result should theoretically eliminate the risk of FAP but, in very few cases, laboratory errors or other circumstances may lead to an inaccurate test result. Thus, some experts suggest that flexible sigmoidoscopy should be performed at ages 18, 25, and 35 years in these individuals, with standard screening thereafter.

After colectomy, continued surveillance of patients with FAP is advised. Ileoscopy is recommended every three to five years. This procedure examines the ileum, or lowest third of the small intestine, and serves to rule out polyps, which may become cancerous with time. Surgical removal of desmoid tumors is invasive but often necessary to prevent reoccurrence. Various nonoperative treatments have been attempted, such as medication and radiation, none of which have yielded consistent results. Additionally, the examination of any remaining rectal tissue by proctoscopy is necessary every six months to assess for signs of rectal cancer.

As with any abdominal surgeries in people affected with FAP, there is a risk of developing desmoid tumors after the colectomy. If desmoids are suspected, computed tomography is the recommended imaging study. MRI may also be used in certain cases.

Surveillance of the upper GI tract, even after total proctocoloectomy, is appropriate due to the incidence of tumors in this area previously discussed.


Without colectomy, the prognosis for individuals with FAP is very poor. Patients who have not undergone colectomy develop colorectal cancer at an average age of 39 years. The majority of untreated people die from colorectal cancer by the age of 42 years. For those who do undergo a colectomy, prognosis is variable, depending on development and progression of other tumors. For example, desmoids can also be detrimental to those affected with FAP, accounting for 11–31% of all mortality in these individuals.



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Lynch, Henry T., and Thomas C. Smyrk. "Hereditary Colorectal Cancer." Seminars in Oncology 26, no. 5 (October 1999): 478–484.

Olson, Sharon J., and Kristin Zawacki. "Hereditary Colorectal Cancer." Clinical Genetics 35, no. 3 (September 2000): 671–685.


Colon Cancer Alliance. 175 Ninth Ave. New York, NY 10011. (212) 627-7451. <http://ccalliance.org>.

Colorectal Cancer Network. PO Box 182, Kensington, MD 20895-0182. (301) 879-1500. <http://www.colorectalcancer.net>.

Hereditary Colon Cancer Association (HCCA). 3601 N 4th Ave., Suite 201, Sioux Falls, SD 57104. (800) 264-6783. <http://hereditarycc.org>.


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Mary E. Freivogel, MS