Attenuated familial adenomatous polyposis

Synonyms

5

Overview

Attenuated familial adenomatous polyposis is a rare, inherited condition that causes extra tissue (polyps) to form in your large intestine (colon) and rectum. Polyps can also occur in the upper gastrointestinal tract, especially the upper part of your small intestine (duodenum). 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.

Most people with familial adenomatous polyposis eventually need surgery to remove the large intestine to prevent cancer. The polyps in the duodenum also can develop cancer, but they can usually be managed by careful monitoring and removing polyps regularly.

Symptoms

  • Benign or malignant tumors of the duodenum (a section of the small intestine)
  • Adenomatous colonic polyposis
  • Intestinal polyposis
  • Abdominal bleeding
  • Diarrhea
  • Cramping abdominal pain
  • Weight loss
  • Rectal bleeding
  • Anemia
  • Other symptoms of FAP

Causes

Mutations in the APC gene cause both classic and attenuated familial adenomatous polyposis and is inherited in an autosomal dominant manner. 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.

The abnormal gene causes hundreds or even thousands of polyps to grow in your colon and rectum, usually starting by your mid-teens. The polyps are nearly 100 percent certain to develop into colon cancer or rectal cancer by the time you're in your 40s.

Familial adenomatous polyposis can cause other complications:

  • Duodenal polyps. These polyps grow in the upper part of your small intestine and may become cancerous. But with careful monitoring, duodenal polyps can often be detected and removed before cancer develops.
  • Periampullary polyps. These polyps occur where the bile and pancreas ducts enter the duodenum (ampulla). Periampullary polyps might become cancerous but can often be detected and removed before cancer develops.
  • Desmoids. These noncancerous masses can arise anywhere in the body but often develop in the stomach area (abdomen). Desmoids can cause serious problems if they grow into nerves or blood vessels or exert pressure on other organs in your body.
  • Other cancers. Rarely, FAP can cause cancer to develop in your thyroid gland, central nervous system, adrenal glands, liver or other organs.
  • Noncancerous skin tumors.
  • Noncancerous bone tumors.
  • Pigment changes in the retina of your eye.
  • Dental abnormalities.

 

Diagnosis

AFAP is generally managed with regular screening to detect if and when polyps develop. Individuals diagnosed with FAP or AFAP are not only at risk for colorectal cancer but may also have an increased risk over the general population for duodenal, gastric, pancreatic, hepatobiliary, thyroid and brain cancer. 

Treatment

Attenuated familial adenomatous polyposis (AFAP) is generally managed with regular screening to detect if and when polyps develop. Screening by colonoscopy has been recommended for affected people starting at age 20 to 25 years. People with polyps may undergo polypectomy (removal of polyps) followed by continued screenings every one to three years, depending on the number of polyps. A prophylactic colectomy (removal of all or part of the colon) may be considered in people with too many adenomas to remove or those who cannot undergo screening. About one third of people with AFAP have few enough colon polyps that screening with periodic polypectomy is sufficient.

Because individuals with AFAP can also develop duodenal adenomas and other cancers, upper endoscopy is typically recommended starting at age 20 to 30 years and then every one to three years, depending on the number of polyps. There is currently no consensus on screening for tumors that occur outside of the colon, so it has been suggested that affected individuals are managed as if they have classic FAP.

A number of drugs such as celecoxib and sulindac reportedly have been successful at reducing the number and the size of polyps in affected people, but these drugs generally help to prevent further complications and are not considered adequate treatment.

Resources

  • NIH
  • Mayo Clinic
  • Genetics Home Reference