About familial adenomatous polyposis

What is familial adenomatous polyposis?

Familial adenomatous polyposis (FAP) is an inherited disorder characterized by cancer of the large intestine (colon) and rectum. People with the classic type of familial adenomatous polyposis may begin to develop multiple noncancerous (benign) growths (polyps) in the colon as early as their teenage years. Unless the colon is removed, these polyps will become malignant (cancerous). The average age at which an individual develops colon cancer in classic familial adenomatous polyposis is 39 years. Some people have a variant of the disorder, called attenuated familial adenomatous polyposis, in which polyp growth is delayed. The average age of colorectal cancer onset for attenuated familial adenomatous polyposis is 55 years.

In people with classic familial adenomatous polyposis, the number of polyps increases with age, and hundreds to thousands of polyps can develop in the colon. Also of particular significance are noncancerous growths called desmoid tumors. These fibrous tumors usually occur in the tissue covering the intestines and may be provoked by surgery to remove the colon. Desmoid tumors tend to recur after they are surgically removed. In both classic familial adenomatous polyposis and its attenuated variant, benign and malignant tumors are sometimes found in other places in the body, including the duodenum (a section of the small intestine), stomach, bones, skin, and other tissues. People who have colon polyps as well as growths outside the colon are sometimes described as having Gardner syndrome.

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. Fewer than 100 polyps typically develop, rather than hundreds or thousands. The autosomal recessive type of this disorder is caused by mutations in a different gene than the classic and attenuated types of familial adenomatous polyposis.

How common is familial adenomatous polyposis?

The reported incidence of familial adenomatous polyposis varies from 1 in 7,000 to 1 in 22,000 individuals.

What genes are related to familial adenomatous polyposis?

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

Mutations in the MUTYH gene cause autosomal recessive familial adenomatous polyposis (also called MYH-associated polyposis). Mutations in this gene prevent cells from correcting mistakes that are made when DNA is copied (DNA replication) 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.

How do people inherit familial adenomatous polyposis?

Familial adenomatous polyposis can have different inheritance patterns.

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

When familial adenomatous polyposis results from mutations in the MUTYH gene, it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.

How common is familial adenomatous polyposis?

The reported incidence of familial adenomatous polyposis varies from 1 in 7,000 to 1 in 22,000 individuals.

What genes are related to familial adenomatous polyposis?

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

Mutations in the MUTYH gene cause autosomal recessive familial adenomatous polyposis (also called MYH-associated polyposis). Mutations in this gene prevent cells from correcting mistakes that are made when DNA is copied (DNA replication) 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.

How do people inherit familial adenomatous polyposis?

Familial adenomatous polyposis can have different inheritance patterns.

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

When familial adenomatous polyposis results from mutations in the MUTYH gene, it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.

What are the symptoms for familial adenomatous polyposis?

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.

What are the causes for familial adenomatous polyposis?

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.

What are the treatments for familial adenomatous polyposis?

If you have a few small polyps, your Mayo Clinic doctor can remove them during your colonoscopy exam. Eventually, though, polyps may become too numerous to remove individually. To prevent cancer, Mayo specialists recommend surgery for familial adenomatous polyposis, usually by your late teens or early 20s. Surgery may not be required for attenuated FAP.

Surgery doesn't cure FAP. Polyps can continue to form in the remaining or reconstructed parts of your colon, stomach and small intestine. But with careful monitoring, these polyps usually can be found and removed during colonoscopy before becoming cancerous.

Minimally invasive colorectal surgery

At Mayo Clinic, most colorectal surgery is done using minimally invasive (laparoscopic) techniques. Laparoscopic surgery is performed through several small incisions that require just a stitch or two to close. Minimally invasive surgery usually shortens your hospital stay and allows you to recover more quickly.

Mayo Clinic specialists use these surgeries to treat familial adenomatous polyposis and its complications:

  • Ileal pouch-anal anastomosis (J-pouch) surgery. The colon and rectum are removed while preserving your anus, allowing you to have normal bowel movements. At Mayo Clinic, J-pouch surgery is the preferred treatment for FAP. J-pouch surgery can affect fertility. Mayo medical geneticists and reproductive gynecologists advise prospective parents about their options.
  • Total colectomy. The colon is removed while preserving your rectum and anus, allowing you to have normal bowel movements. Mayo specialists consider colectomy only if you don't have polyps in your rectum.
  • Continent ileostomy. Mayo specialists may recommend this surgery if your rectum or anus is damaged and J-pouch surgery isn't feasible. In this procedure, your small intestine is connected to the outside body through an opening (stoma) on your abdomen. Bowel movements that would normally have emptied through the rectum are collected in a waste bag that attaches at the stoma. Mayo Clinic has a team of wound and stoma care specialists who provide you with counseling before surgery and education and compassionate support afterward.

Follow-up treatment

At Mayo Clinic, you are screened regularly and treated for complications of familial adenomatous polyposis that can develop after colorectal surgery, including:

  • Duodenal polyps and periampullary polyps. Mayo specialists may recommend surgery in some cases to remove the entire duodenum because these types of polyps can progress to cancer.
  • Desmoid tumors. Mayo specialists use a combination of medications, including nonsteroidal anti-inflammatory drugs, anti-estrogen, chemotherapy and, in some cases, surgery.
  • Noncancerous bone tumors. Mayo surgeons can remove these tumors for pain relief or cosmetic reasons.

What are the risk factors for familial adenomatous polyposis?

Your risk of familial adenomatous polyposis is higher if you have a parent, child, brother, or sister with the condition.

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