Familial adenomatous polyposis

Familial adenomatous polyposis ( FAP syn., polyposis coli) is an autosomal dominantly inherited disorder in which there is a massive infestation of the colon with polyps. If left untreated, the probability of degeneration of one or more of these polyps to colon cancer is nearly 100 %.

Frequency

The disease is rare. It is estimated that 5-10 affected by 100,000 people by the gene mutation.

Cause

Cause of the disease is a germline mutation of the APC gene ( Adenomatous polyposis of the colon). One of the two alleles of this located on chromosome 5q21 - q22 5 tumor suppressor gene is inactivated it. If now another (somatic ) mutation in addition, also the other allele may be inactivated. In healthy binds APC protein to β -catenin and mediates ubiquitination via its degradation in the proteasome. Can not be β -catenin ubiquitinyliert, wherein the cells contain large amounts of β -catenin. This translocated into the nucleus where it acts, together with other factors as a transcription factor. Wherein cell growth is promoted and made ​​telomerase immortalized cells (which prevents cell death ). It comes to an accelerated expiry of the adenoma -carcinoma sequence.

Clinical manifestations

The polyps of the colon typically occur in the third decade of life. Symptoms follow, however, usually only in the fourth decade of life. These consist of pera tional blood or mucus departures and abdominal pain. At the time of first symptoms may become evident invasive cancer. Likewise, there are often polyps of the stomach or duodenum. The latter also have a tendency to degeneration.

Methods of investigation

The earliest feature of the disease existing proliferation of the pigment epithelium of the iris can be seen at birth. For reliable diagnosis, the family members should be examined by colonoscopy, as they also show the typical image of a variety of polyps.

Therapy and Outcome

By complete removal of the colon, the development of colon cancer can be excluded. In this case, a reservoir of shares of the ileum is formed. Alternatively, an incomplete ( subtotal ) colon removal are carried out, wherein the rectum is retained. This reached regarding continence and quality of life better results. However, it comes in 10% of cases to a rectal cancer.

In some cases, however, occur in the small intestine carcinomas and progressively growing Desmoidtumore.

Attenuated familial adenomatous polyposis ( AFAP )

The AFAP is a special form of FAP. It is a milder form, in which the clinical symptoms does not develop so quickly. As a cause mutations of the APC gene, but also the MUTYH gene to be found. In patients with AFAP there is an average of only from 31 years old to symptoms. Polyps are also less available and are limited to a number of less than 100 Mostly these polyps found in the ascending colon ( ascending colon ).