What is FAP?

Familial adenomatous polyposis (FAP) is an inherited condition that primarily affects the gastrointestinal tract. This disorder leads to hundreds or thousands of polyps inside the colon and rectum (less often in the stomach and small intestine). Symptoms typically appear in teenagers or young adults. Other names for this condition include hereditary polyposis of the colorectum, familial polyposis, and Gardner’s syndrome. 

Familial adenomatous polyposis is an inherited condition caused by a mutation on chromosome 5. FAP is characterized by hundreds to thousands of polyps in the gastrointestinal tract (primarily the colon and rectum). These polyps are at increased risk for malignancy. Polyps begin to appear during teen years and often become cancerous by age 40.

Fig 1. A: Appearance of FAP inside the colon; B: Endoscopic image of polyposis; C: Enlargement of polyps in the colon

Polyps (abnormal mushroom-like growths) may vary in size from less than one tenth of an inch to 1–2 inches. They may be large enough to block part of the intestine. If patients with FAP are left untreated, one or more of these polyps may develop into cancer. FAP may also be associated with benign tumors of the skin, soft connective tissue, and bones. It is caused by a mutation in a gene called APC. In some people FAP may be inherited, whereas in others it is not (sporadic).

Fig 2. Illustrative comparison of polyp size

Attenuated FAP

Some families are affected with attenuated FAP (AFAP). This is a mild (or attenuated) form of FAP in which affected individuals develop fewer polyps at a later age than those with typical FAP. Although people with AFAP tend to develop colon cancer at a later age than individuals with typical FAP, they still have a near 100% lifetime risk of colon cancer. If AFAP is suspected within a family, it is important that family members be screened with colonoscopy rather than flexible sigmoidoscopy because polyps are not evenly distributed throughout the colon. Because the number of polyps and age of onset can vary greatly from one family member to another in a family with AFAP, screening should begin at age 11.

Other Symptoms Associated with FAP
Individuals with FAP often develop polyps in organs other than the colon, such as stomach and small intestine. Although most polyps that develop in the stomach and small intestine are benign, cancer may develop in them.  Desmoid tumors may also develop. Young children affected with FAP have a small increased risk for hepatoblastoma, a liver tumor. Tumors may also occur in the thyroid gland, adrenal gland, bile ducts, and pancreas. Affected individuals may also have some, or all, of the following: lumps or bumps on the bones of the legs, arms, skull and jaw; cysts of the skin; teeth that do not erupt when they should; and freckle-like spots on the inside lining of the eye. Thus, physicians recommend that patients continue with life-long follow-up examination for cancer prevention.

How is FAP Inherited?

People with FAP have a 50% chance of passing the condition to each of their children. The condition can be passed on even if the patient has had his or her own colon removed. Children who do not inherit the condition from their parent cannot pass it to their own children.

About one third of people with FAP do not have an affected parent. An individual who is the first in the family to have the condition has a new or spontaneous mutation. Individuals with new mutations can pass FAP to their children

Figure 3. FAP family pedigree

  1. George has FAP, his wife Susan is unaffected. They have 3 children, George, Jr., Stephen, and Carol. All were at 50% risk of developing FAP. George, Jr., and Carol are affected.
  2. George, Jr. and his wife Connie have 2 children. Both children had a 50% chance of inheriting FAP. Their daughter Alice is affected.
  3. Stephen and his wife Gloria have 2 children. Because Stephen is unaffected, there was no risk to his children of developing FAP.
  4. Carol and Bill have 3 children. Each child had a 50% chance of inheriting FAP and two are affected; son Billy is not. 

Genetic Testing and Counseling for FAP 

Genetic counseling is available and recommended for individuals with FAP and for their family members. Genetic counselors will explain the inheritance pattern of FAP, discuss which family members are at risk for developing the condition, and provide necessary information regarding genetic testing. Counseling services are available through genetic and oncology departments in many hospitals. To make an appointment with a member of the Johns Hopkins professional medical team or to speak with someone at the Colorectal Cancer Risk Assessment Service, please call (410) 614-LIFE (5433). Also, it is recommended that FAP families contact registries for access to resources and for help with identification of family members at risk.

Genetic testing is available for Familial Adenomatous Polyposis (FAP), Hereditary Nonpolyposis Colorectal Cancer (HNPCC), and APC I1307K.

The altered gene that causes FAP in most patients is now known.

Fig 4. Chromosome 5 for FAP

A blood test can locate the change in the APC gene, which is causing the disease in about 80% of families with FAP. In these families, children can learn if they have inherited the changed APC gene from their parent with FAP. If a child does have the gene mutation, he or she will eventually develop FAP. The mutation in the APC gene cannot be detected in about 20% of families with FAP. Children in these families must continue to have regular colon screening according to the guidelines for families in which a gene mutation could not be found.

The test requires a small blood sample. The gene test results will influence the future management of individuals who are at risk for FAP. For example, if the test shows that a person does not have the APC gene mutation known in the family, he or she can avoid many unnecessary colon examinations. If the test shows that a person does have the gene mutation, then the physician will need to be alerted to schedule colon examinations at least yearly and to plan for future treatment when polyps develop.

Is insurance discrimination a risk for those seeking genetic testing?
With any gene test, there is a risk of insurance (life or health) or employment discrimination. At this time, federal laws offer some protection against the discrimination against people who already have medical insurance through a group health plan. Some states have other laws to protect people, but the laws on insurance and employment discrimination vary from state-to-state. The Americans with Disabilities Act may protect people with a positive gene test result from discrimination in the work place. These issues will be carefully explained during the genetic counseling session.

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