Familial adenomatous polyposis

Familial adenomatous polyposis, often called FAP, is an inherited colorectal cancer syndrome. Cancer usually develops in the lower part of the digestive system, including the colon (large intestine) and rectum. People with the classic type of familial adenomatous polyposis begin to develop multiple benign polyps (growths) in the large intestine as early as their teenage years. Some people, however, have a variant of the disorder—called attenuated familial adenomatous polyposis—in which polyp growth is delayed, typically until adulthood. The average age of onset for the attenuated polyposis variant is about 55, compared to onset 10 to 15 years earlier among people with classic familial adenomatous polyposis (average age of onset is about 39).

In people with classic familial adenomatous polyposis, the number of polyps increases with age and can include hundreds to thousands of polyps. Unless the colon is removed, these polyps will become malignant (cancerous). Also, of particular significance are desmoid tumors. These fibrous tumors usually occur in the covering of the intestines and may be initiated by abdominal surgery. With classic familial adenomatous polyposis and its attenuated variant, other growths, both benign and malignant, are sometimes found in other places in the body, especially the duodenum (part of the small intestine), stomach, bones, and other tissues.

A milder type of familial adenomatous polyposis, called autosomal recessive familial adenomatous polyposis, has also been identified. People with the autosomal recessive type of this disorder have fewer polyps than those with the classic type, typically less than 100, rather than hundreds or thousands. The autosomal recessive type of this disorder is caused by mutations in a different gene than classic and attenuated types of familial adenomatous polyposis.

In the United States, familial adenomatous polyposis affects about 1 in 30,000 people, with 800-1,000 new cases detected each year.

Mutations in the APC and MUTYH genes cause familial adenomatous polyposis.

Mutations in the APC gene affect the cell's ability to maintain normal cell growth and function. Cell overgrowth results from mutations in the APC gene and leads to the colon polyps seen in familial adenomatous polyposis. Although people with mutations in the APC gene will develop colorectal cancer, the number of polyps and the time frame in which they will become malignant depends on the location of the mutation in the gene. Mutations in the APC gene cause classic and attenuated familial adenomatous polyposis.

Mutations in the MUTYH gene inhibit cells from correcting mistakes that are made when DNA is copied (replicated) in preparation for cell division. As these mistakes build up in a person's DNA, the likelihood of cell overgrowth increases, leading to colon polyps and the possibility of colon cancer. Mutations in the MUTYH gene cause autosomal recessive familial adenomatous polyposis (also called MYH-associated polyposis).

Familial adenomatous polyposis can have different inheritance patterns and different genetic causes.

When this condition results from mutations in the APC gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition.

Mutations in the MUTYH gene are inherited in an autosomal recessive pattern, which means two copies of the gene must be altered for a person to be affected by the disorder. Most often, the parents of a child with an autosomal recessive disorder are not affected but are carriers of one copy of the altered gene.

You may find the following resources about familial adenomatous polyposis helpful.

• NIH Publications - National Institutes of Health (3 links)
• MedlinePlus - Health Information (3 links)
• Educational resources - Information pages (6 links)
• Patient support - For patients and families (3 links)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

• Gene Reviews - Clinical summary
• Gene Tests - DNA tests ordered by healthcare professionals (2 links)
• PubMed - Recent literature
• OMIM - Genetic disorder catalog (2 links)

See How are genetic conditions and genes named? in the Handbook.

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These links provide additional genetics resources that may be useful.

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autosomal ; autosomal dominant ; autosomal recessive ; benign ; cancer ; carrier ; cell division ; colon ; colon polyp ; colorectal ; digestive ; digestive system ; DNA ; duodenum ; familial ; familial polyposis ; gene ; inheritance pattern ; intestine ; mutation ; polyp ; polyposis ; recessive ; rectum ; teenage ; tumor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.