Adenomatous Polyposis Syndromes
Attenuated familial polyposis syndrome (AFAP)
AFAP-affected patients develop a much lower number of polyps, commonly less than 100. The risk of cancer development is very high, but under 100%. Polyps and cancer appear 10 to 15 years later, on average, than in FAP (usually when the patient is in their early 30’s). Polyps tend to be present in the proximal colon, although rectal-sparing is common. Duodenal adenomas and fundic gland polyps are also frequently described in AFAP patients.
Screening for AFAP is tailored to the individual family history. A full colonoscopy should be performed; flexible-sigmoidoscopy is not sufficient due to the common proximal location of the polyps. Surveillance should start at age 25 or 10 years earlier than the earliest diagnosis in the family and continue annually, or at recommended intervals. Colectomy is recommended when polyps become difficult to manage endoscopically.
Genetic testing and AFAP
AFAP is due to germ-line mutations in the APC gene at the proximal and distal extremes of the gene or in certain areas of exon 9. Therefore, Genetic testing involves APC gene mutation analysis. Hypothetically, the different phenotype of AFAP might be due to attenuated alleles producing mutant peptides that are too short or otherwise unable to interfere with the product of the normal allele to form the functional heterodimer, or they would be only partially functioning peptides.
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