Definition of Attenuated familial adenomatous polyposis

Reviewed on 3/29/2021

Attenuated familial adenomatous polyposis: An inherited predisposition to colorectal cancer characterized by fewer than 100 adenomatous polyps in the colon and rectum. It is said to be attenuated because there are fewer polyps than in classic familial adenomatous polyposis (FAP). People with attenuated familial adenomatous polyposis (AFAP) also tend to be older at the diagnosis of their polyps (average age of 44 years) and cancer (average age of 56 years), 10 to 15 years later than in classic FAP. The right side of the colon tends to be involved in AFAP and rectal involvement is rare. AFAP is transmitted in an autosomal dominant manner.

People with AFAP often belong to families that also have members with classic FAP. As in FAP, there may also be polyps higher up in the intestinal tract in the duodenum and stomach and an elevated risk of stomach, liver, and breast cancer. And as in FAP, AFAP is associated with mutations in the APC gene (in some cases). APC gene testing can therefore be informative in people suspected of having AFAP. If APC testing is negative, then genetic testing for MYH mutations (another hereditary cause of colorectal cancer) may be warranted.

It has been recommended that AFAP patients have colonoscopy rather than sigmoidoscopy because the adenomatous polyps are predominantly right-sided and beyond the reach of a sigmodoscope. The role for and timing of prophylactic colectomy (precautionary removal of the colon) in AFAP is controversial.

On the molecular level, mutations in the APC gene in FAP and AFAP have been found in three different regions of the gene:

  1. At the 5' end of the APC gene, spanning exons 4 and 5;
  2. Within exon 9 of the APC gene; and
  3. At the 3' end of the APC gene.
It has been proposed that mutations in region 1 are associated with a great range in the number of colorectal polyps (from 2 to more than 500) and with the presence of upper intestinal polyps; that mutations in region 2 are associated with the presence of from 1 to 150 colorectal polyps, but no upper intestinal polyps; and that mutations in region 3 are associated with the presence of less than 50 colorectal polyps.


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