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Clinical
Issues in Diagnosis & Management of Familial Adenomatous Polyposis
(FAP) FAP is a genetic cancer syndrome associated with multiple (hundreds of) colon polyps that eventually lead to the development of colon cancer. In contrast to hereditary non-polyposis colorectal cancer (HNPCC) where polyps are rare, in FAP polyps begin to appear in childhood or adolescence and cancer itself is generally diagnosed between 20 and 50 years with the average age for detection of a malignancy of 39 years. FAP occurs in about 1 in 30,000 individuals and accounts for about 1 in 200 cases of all colorectal cancers. Clinical diagnosis is made in individuals with either >100 adenomatous polyps or numerous but <100 polyps as well as a first degree affected with FAP. A milder "attenuated" form may be suspected in individuals with fewer colonic polyps (average # 30) and a family history of colon cancer diagnosed in other individuals at or before the age of 50. A more medically complex form of FAP is Gardner syndrome (GS) which is not only associated with colon polyps but also osteomas, soft tissue tumors and a very specific tumor known as a desmoid tumor. A clinically silent but helpful diagnostic clue found in some individuals with FAP is congenital hypertrophy of the retinal pigment epithelium (CHRPE) which can be found on a focused ophthalmolgic exam. Although the adenomatous polyps are usually found in the large intestine, some individuals with FAP are found to have poyps in the fundus of the stomach or duodenum. Unlike HNPCC which is associated with mutations in a variety of mismatch repair genes, FAP is associated with mutations in a single gene called APC. The majority (about 80%) of clinically affected individuals will have an APC mutation resulting in premature truncation of the protein product that is detectable by in vitro assay. This molecular technology now permits DNA testing for asymptomatic at-risk family members as well as for individuals with attenuated or atypical features of FAP. As with most DNA-based testing, it is ideal to first test a known affected individual in order to provide the most accurate risk information. For an adult with a history or family history suggestive of possible FAP, one should consider:
For a patient with known FAP or multiple polyps, one should consider:
Possibly the most difficult management issues revolve around caring for children or at risk family members who have not yet been diagnosed with FAP. Clearly offspring of affected persons have a 50% risk of developing the disease and, unless the affected person has a de novo mutation causing FAP (this is seen about 20-25% of the time), siblings are also at 50% risk. Current recommendations for individuals at 50% risk for FAP are to have sigmoidoscopy beginning at 10 to 12 years of age and, if polyps are discovered, annual colonoscopy until the definitive surgery (colectomy) is performed. We encourage young adults who are clearly affected to consider surgery between 18 and 22 years of age because the risk for malignancy increases steadily after that time. For people who choose to undergo DNA testing, it is first important to establish if a mutation can be found in an affected family member. If such a mutation is identified, then others can benefit tremendously from testing. Those family members who test negative do not need to undergo annual screening whereas those who test positive will be able to take the necessary steps to prevent colon cancer. In general, such testing is best done through a genetic center knowledgeable about the technology and where informed consent and risk/benefit discussions can be held. Although, as a general rule clinicians are reluctant to consider presymptomatic testing of minors, because of the potential for early onset of adenomatous polyps and real risk for malignant transformation, this is a condition for which testing of minors, in some circumstances, can be justified. The benefits of testing at risk children include the opportunity to forego annual sigmoidoscopies (when the test is negative and the family is "molecularly informative") and long term planning for prophylactic colectomy when the test is positive. Support services are available to families or individuals facing a possible or confirmed diagnosis of FAP and two such groups that may offer help in this regard are: Intestinal Multiple Polyposis and
Colorectal Cancer (IMPACC) United Ostomy Association, Inc. |
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