Mutyh-associated polyposis (map) D12.6

Autosomal-recessive inherited adenomatous polyposis Disease which, like familial adenomatous polyposis (FAP), is characterized by the occurrence of multiple polyps of the colon (histologically mostly adenomas). MUTYH is the acronym for "MutY DNA glycosylase" of a DNA glycolase.

1% of the population are carriers of the MUTYH gene mutation. The main consequence of the inheritance is that - in contrast to FAP - children can be genetically burdened without the parents showing phenotypic signs. However, both parents must be carriers of the genetic make-up. As a result of the inheritance, siblings of a MAP patient have a 25% risk of also being affected by this genetic disease. Children of a MAP patient are always carriers of this hereditary disease.

Children of a MAP patient therefore have a 0.5% probability (homozygous genetic material and heterozygous genetic material; 1% that two possible genotypes reduce to 0.5%).

Both parents of the patients carry the mutated gene only on one gene copy, the other gene copy is unchanged and can compensate for the mutation. They are therefore healthy, but so-called heterozygous carriers. The siblings of a sick person have a 25% risk of becoming ill as well.

Mutation in the MUTYH gene (MYH gene) on chromosome 1p34.1 The MUTYH gene encodes a protein, a glycosylase, which is located in the cell nucleus and the mitochondria of the cell and repairs DNA damage.

The base pairs usually occur in only two forms: adenine with thymine and guanine with cytosine. Due to oxidative damage, guanine can form a base pair with adenine. The protein formed by the MUTYH gene, MUTYH glycosylase, recognizes this mismatch and repairs it. Mutations in the MUTYH gene lead to a defect of the MUTYH glycosylase and to a disturbed DNA repair. MUTYH glycolase is overexpressed in CD4-T cells, in the prostate, colon and rectum.

The mean age of onset of colon cancer (especially in the proximal part of the colon) with MAP is 50 years. They develop preferentially in the proximal part of the colon.

A homozygous carrier of a MUTYH gene mutation is recommended to undergo regular colonoscopies from the age of 30.

There is a high risk of degeneration for colorectal carcinoma.

In general, the clinical course is similar to that of the attenuated, mild form of FAP (also known as AFAP). As with AFAP, the polyps usually appear later and less numerous than in classic FAP. In addition, the risk of degenerative colon cancer in untreated patients often does not increase until the 5th or 6th decade of life.

Adenomas in the duodenum occur less frequently with AFAP than with FAP. Extragastrointestinal disease symptoms are largely absent. In rare cases, colorectal carcinomas are associated with pilomatrices.

Among the polyps, hyperplastic as well as serrated adenomas are frequently found.