Classically, FAP is characterized by multiple (>100) adenomatous polyps in the colon and rectum developing after the first decade of life. Variant features in addition to the colonic polyps may include polyps in the upper gastrointestinal tract, extraintestinal manifestations such as congenital hypertrophy of retinal pigment epithelium, osteomas and epidermoid cysts, supernumerary teeth, desmoid formation, and other malignant changes such as thyroid tumors, small bowel cancer, hepatoblastoma, and brain tumors, particularly medulloblastoma. For additional information, refer to Table 5.
Table 5. Extracolonic Tumor Risks in Familial Adenomatous Polyposis
Adapted from Giardiello et al., Jagelman et al., Sturt et al., Lynch et al., B�low et al., Burt et al., and Galiatsatos et al.
a The Leeds Castle Polyposis Group.
|Malignancy||Relative Risk||Absolute Lifetime Risk (%)|
FAP is also known as familial polyposis coli, adenomatous polyposis coli (APC), or Gardner syndrome (colorectal polyposis, osteomas, and soft tissue tumors). Gardner syndrome has sometimes been used to designate FAP patients who manifest these extracolonic features. However, Gardner syndrome has been shown molecularly to be a variant of FAP, and thus the term Gardner syndrome is essentially obsolete in clinical practice.
Most cases of FAP are due to mutations of the APC gene on chromosome 5q21. Individuals who inherit a mutant APC gene have a very high likelihood of developing colonic adenomas; the risk has been estimated to be more than 90%.[1,9,10] The age at onset of adenomas in the colon is variable: By age 10 years, only 15% of FAP gene carriers manifest adenomas; by age 20 years, the probability rises to 75%; and by age 30 years, 90% will have presented with FAP.[1,9,10,20,21] Without any intervention, most persons with FAP will develop colon or rectal cancer by the fourth decade of life.[1,9,10] Thus, surveillance and intervention for APC gene mutation carriers and at-risk persons have conventionally consisted of annual sigmoidoscopy beginning around puberty. The objective of this regimen is early detection of colonic polyps in those who have FAP, leading to preventive colectomy.[22,23]
The early appearance of clinical features of FAP and the subsequent recommendations for surveillance beginning at puberty raise special considerations relating to the genetic testing of children for susceptibility genes. Some proponents feel that the genetic testing of children for FAP presents an example in which possible medical benefit justifies genetic testing of minors, especially for the anticipated 50% of children who will be found not to be mutation carriers and who can thus be spared the necessity of unpleasant and costly annual sigmoidoscopy. The psychological impact of such testing is currently under investigation and is addressed in the Psychosocial Issues in Hereditary Colon Cancer Syndromes: Lynch Syndrome and Familial Adenomatous Polyposis section of this summary.