Familial Adenomatous Polyposis
Familial Adenomatous Polyposis
National Organization for Rare Disorders, Inc.
It is possible that the main title of the report Familial Adenomatous Polyposis is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.
- adenomatous polyposis of the colon (APC)
- familial multiple polyposis
- hereditary polyposis coli
- multiple polyposis of the colon
Related Disorders List
Information on the following diseases can be found in the Related Disorders section of this report:
Familial adenomatous polyposis (FAP) is a rare inherited cancer predisposition syndrome characterized by hundreds to thousands of precancerous colorectal polyps (adenomatous polyps). If left untreated, affected individuals inevitably develop cancer of the colon and/or rectum at a relatively young age. FAP is inherited in an autosomal dominant manner and caused by abnormalities (mutations) in the APC gene. Mutations in the APC gene cause a group of polyposis conditions that have overlapping features: familial adenomatous polyposis, Gardner syndrome, Turcot syndrome and attenuated FAP.
Classic FAP is characterized by hundreds to thousands of colorectal adenomatous polyps, with polyps appearing on average at age 16 years. Without colectomy, affected individuals usually develop colorectal cancer by the third or fourth decade of life. FAP is also associated with an increased risk for cancer of the small intestine including the duodenum, and cancer of the thyroid, pancreas, liver (hepatoblatoma), central nervous system (CNS), and bile ducts, although these typically occur in less than 10% of affected individuals.
Individuals with CNS tumors and colorectal polyposis have historically been defined as Turcot syndrome. Two-thirds of cases of Turcot syndrome develop from mutations in the APC gene. The remaining cases develop from mutations in the genes that cause hereditary non-polyposis colorectal cancer (HNPCC) also known as Lynch syndrome. Mutations in the APC gene are more commonly associated with medulloblastoma; mutations in the genes that cause HNPCC are more commonly associated with glioblastoma.
Extracolonic manifestations are variably present in FAP, including polyps of the stomach, duodenum and small bowel; and osteomas (bony growths), dental abnormalities, congenital hypertrophy of the retinal pigment epithelium (CHRPE), and soft tissue tumors including epidermoid cysts, fibromas and desmoid tumors. About 5% of individuals with FAP experience morbidity and/or mortality from desmoid tumors. The term Gardner syndrome is often used when colonic polyposis is accompanied by clinically obvious osteomas and soft tissue tumors.
Attenuated FAP is a variant of familial adenomatous polyposis. The disorder is characterized by an increased risk for colorectal cancer (although lower risk than classical FAP) but with fewer polyps (average of 30) and later age of onset of polyps and cancer than is typically seen in classic FAP. Extra-colonic manifestations are also associated with attenuated FAP.
Familial adenomatous polyposis is caused by germline (present in the first cell of the embryo) mutations in the APC gene and is inherited in an autosomal dominant manner, meaning that on average 50% of children of an affected parent will have the disease passed on to them.
Dominant genetic disorders occur when only a single copy or allele of a specific gene is mutated, thereby causing a particular disease. The abnormal gene can be inherited from either parent or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy. The risk is the same for males and females.
Familial adenomatous polyposis affects males and females in equal numbers. It occurs in approximately one in 5,000 to 10,000 individuals in the United States and accounts for about 0.5% of all cases of colorectal cancer. One estimate suggests that familial adenomatous polyposis affects 50,000 American families. According to national registries, familial adenomatous polyposis occurs in 2.29-3.2 per 100,000 individuals.
Features of the following disorders can be similar to those of the APC gene-associated polyposis conditions. Comparisons may be useful for a differential diagnosis:
MYH gene-associated polyposis (MAP) is an autosomal recessive cancer predisposition syndrome with a colonic phenotype similar to attenuated FAP. Mutations in the MYH gene are associated with this condition.
Hereditary non-polyposis colon cancer (HNPCC) or Lynch syndrome is an autosomal dominant cancer predisposition syndrome that causes a very high risk for colorectal and endometrial cancer in addition to an increased risk for cancers of the ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin. Individuals with Lynch syndrome most often exhibit only one or several precancerous polys of the colon. Thus, Lynch syndrome is sometimes difficult to distinguish from attenuated FAP, as some individuals with attenuated FAP may have a low number of polyps.
Peutz-Jeghers syndrome is an autosomal dominant genetic condition characterized by multiple benign hamartomatous polyps (Peutz-Jeghers polyps) in the gastrointestinal system. Hamartomatous polyps have a much lower risk of becoming cancerous compared to adenomatous polyps. These polyps occur most often in the small intestine but also occur in the stomach and large intestine. Affected individuals also have dark skin discoloration, like freckles or spots around the lips and on the face but much darker,These pigmented spots often presents in childhood and can be also be seen around the eyes, and nostrils, and on the mucous membranes of the mouth and in the perianal area. Affected individuals have an increased risk for intestinal and other cancers. This condition can be distinguished from FAP by clinical features and histology (microscopic examination) of the polyps. (For more information on this disorder, choose "Peutz-Jeghers" as your search term in the Rare Disease Database)
Juvenile polyposis syndrome (JPS) is an autosomal dominant genetic condition characterized by a predisposition to gastrointestinal polyps. The term "juvenile" refers to the type of polyp as opposed to the age of onset. Polyps are usually diagnosed by 20 years of age and are usually benign, although malignant transformation can occur. JPS is associated with mutations in the SMAD4 and BMPR1A genes.
Cronkhite-Canada disease is a very rare acquired (not inherited) disease and is characterized by intestinal polyps, loss of taste and hair, and nail growth problems. It is difficult to treat because of malabsorption that accompanies the polyps. Cronkhite-Canada disease occurs primarily in older people (the average age is 59). There have been fewer than 400 cases reported in the past 50 years, primarily in Japan but also in the U.S. and other countries (For more information on this disorder, choose "Cronkhite-Canada" as your search term in the Rare Disease Database.)
Classical FAP is diagnosed clinically when an individual has 100 or more adenomatous colorectal polyps (typically occurring by the third decade of life) or fewer than 100 polyps and a relative with FAP. Genetic testing for mutations in the APC gene is available to confirm the diagnosis of FAP and the associated conditions. Younger individuals may have fewer polyps. A diagnosis is made in younger people by the presence of the typical polyps and in immediate relative with FAP or by genetic testing.
Partial or complete removal of the colon (colectomy) is usually recommended for individuals with classical FAP at an appropriate age, usually between the late teens and late 30s. Sulindac is a nonsteroidal antiinflammatory drug (NSAID) usually used for arthritis, but is sometimes prescribed for individuals with FAP who have had a colectomy to treat polyps in the remaining rectum. Polyps will almost always regress, but it is uncertain if the cancer risk is changed, so surveillance must be continued.
Removal of duodenal polyps is sometimes recommended if they cause symptoms, are large or contain large numbers of abnormal cells (dysplasia). This is to prevent them from becoming cancerous.
Desmoid tumors are benign, but may cause problems by compressing organs and/or blood vessels in the abdomen. These are treated variously with surgery, NSAIDs, anti-estrogen medications, chemotherapy and/or radiation depending on the details in each case. They are sometimes just followed when they do not grow.
Genetic counseling is recommended for individuals with familial adenomatous polyposis and their at-risk family members. This is very helpful to properly obtain and interpret genetic testing. Affected individuals should be screened clinically and endoscopically on a regular basis in order to identify cancerous and pre-cancerous tumors at an early stage. Colon cancer is virtually always prevented by screening and properly timed colectomy. This is similar for duodenal cancer. Other cancers are usually detected early, rather than prevented.
Prevention therapies (chemoprevention) are presently under study in several institutions. Information on these and other current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
For information about clinical trials conducted in Europe, contact:
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Jasperson, K W, Tuohy TM, Neklason DW and Burt RW.. Hereditary and familial colon cancer. Gastroenterology. 2010; 138(6): 2044-2058.
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van Stolk R, et al., Phase I trial of exisulind (sulindac sulfone, FGN-1 as a chemoprotective agent in patients with familial adenomatous polyposis. Clin Cancer Res. 2000;6:78-89.
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Jasperson KW and Burt, R W. Updated 10/27/11. APC-Associated Polyposis Conditions. In: GeneReviews at Genetests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2011. Available at http://www.genetests.org. Accessed Dec 26, 2013.
National Cancer Institute: Genetics of Colorectal Cancer http://www.cancer.gov/cancertopics/pdq/genetics/colorectal/HealthProfessional/page1 Last modified 12/20/2013. Accessed Dec 26, 2013.
Familial GI Cancer Registry
Mt. Sinai Hospital
Joseph and Wolf Lebovic Health Complex
600 University Avenue
Ontario, M5T 3L9
Johns Hopkins Hereditary Colorectal Cancer Registry
Johns Hopkins Hospital
1830 East Monument Stree
Baltimore, MD 21205
American Cancer Society, Inc.
250 Williams NW St
Atlanta, GA 30303
National Cancer Institute
6116 Executive Blvd Suite 300
Bethesda, MD 20892-8322
M. D. Anderson Cancer Center Hereditary Colorectal Cancer Registry
Dept of Gastrointestinal Oncology
1515 Holcombe Boulevard
P.O. Box 78
Houston, TX 77030
OncoLink: The University of Pennsylvania Cancer Center Resource
3400 Spruce Street
Philadelphia, PA 19104-4283
Strang-Cornell Hereditary Colon Cancer Program
428 East 72nd Street
New York, NY 10021
Rare Cancer Alliance
1649 North Pacana Way
Green Valley, AZ 85614
Genetic and Rare Diseases (GARD) Information Center
PO Box 8126
Gaithersburg, MD 20898-8126
Friends of Cancer Research
1800 M Street NW
Suite 1050 South
Washington, DC 22202
American Society of Clinical Oncology
2318 Mill Road Suite 800
Alexandria, VA 22314
Cancer Support Community
1050 17th St NW Suite 500
Washington, DC 20036
Desmoid Tumor Research Foundation
P.O. Box 273
Suffern, NY 10901
3 St. Andrews Place
London, NW1 4LB
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It is possible that the title of this topic is not the name you selected. Please check the Synonyms listing to find the alternate name(s) and Disorder Subdivision(s) covered by this report
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Last Updated: 1/27/2014
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