Familial adenomatous polyposis
| Classification according to ICD-10 | |
|---|---|
| D12 | Benign neoplasm of the colon, rectum, anal canal, and anus |
| D12.6 | Colon, unspecified Polyposis coli (hereditary) |
| ICD-10 online (WHO version 2019) | |
The familial adenomatous polyposis (FAP) is an autosomal - dominant inherited disease , which is a massive infestation of the colon with polyps comes. If left untreated, the likelihood of one or more of these polyps developing into colon cancer is close to 100%.
frequency
The disease is rare. It is estimated that 5–10 in 100,000 people are affected by the gene mutation.
root 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 tumor suppressor gene located on chromosome 5 5q21-q22 is inactivated. If another (somatic) mutation is added, the other allele can also be inactivated. In healthy individuals, APC protein binds to β-catenin and mediates its degradation in the proteasome via ubiquitinylation . If β-catenin can no longer be ubiquitinylated, the cells contain large amounts of β-catenin. This translocates into the cell nucleus and acts there together with other factors as a transcription factor . This promotes cell growth and produces telomerase , which immortalizes cells (prevents cell death). The adenoma-carcinoma sequence accelerates .
Clinical manifestations
The first colon polyps usually appear in FAP patients between the ages of 10 and 25. The disease can initially go unnoticed for several years. The following symptoms (symptoms) may occur at a later point in time:
- Loss of blood and / or mucus from the intestines
- Diarrhea or constipation, or frequent switching between the two
- Flatulence
- Pain in the abdomen or rectum
- Weight loss
In addition to the classic FAP, there is also a milder variant, the so-called attenuated FAP or AFAP. This is characterized by a later age of onset and usually far fewer polyps (<100) in the large intestine. Despite the milder course, the lifetime risk of colon cancer is similar to that of classic FAP. In some patients, changes outside of the colon, usually benign, are also observed. Sometimes these symptoms appear before the colon polyps. The observation of the changes mentioned below can indicate the presence of an FAP and should always be a reason for further investigations.
In the case of an autosomal dominant inherited disease, the corresponding clinical picture occurs when only one of the two genes created in pairs is changed (mutated). Since you only pass on one gene from a pair of genes to your children, the risk for children of a sick person to inherit the changed gene is 50%. In the case of autosomal dominant inheritance, gender does not play a role in inheritance, i.e. both men and women can have inherited the change or pass it on.
If the responsible mutation has been identified in a person affected, it is possible to test all members of a family for the presence of this mutation as part of a human genetic consultation before the first clinical symptoms are observed (predictive or predictive diagnostics). For proven mutation carriers (carriers) there is a practically 100 percent risk of disease, so they should have intensive preventive or early detection examinations and, if necessary, therapeutic measures with regard to FAP carried out.
Investigation methods
The earliest characteristic of the disease is an increase in the pigment epithelium of the iris at birth . For a reliable diagnosis, the family members should be examined by colonoscopy, as they also show the typical appearance of a large number of polyps.
therapy and progress
So far, the only way to prevent colon cancer from occurring in people with classic FAP has been surgical removal of the colon (colectomy). Today, this operation can almost always be performed in a continence-conserving manner. The time for the operation should be decided individually. In the vast majority of cases, the affected patients lead an unimpaired social, professional and sexual life again after the operation. However, it is important that FAP patients are cared for and operated on at centers that are experienced in treating this condition. The treatment of an affected FAP patient is usually not based on the result of the molecular genetic diagnosis, but on the clinical course, that is, on the number, growth rate and tissue diagnosis of the polyps.
In addition to surgical treatment, a drug therapy attempt can also be discussed in some patients with mild forms of FAP or if the rectum has been preserved after a colectomy: With the drug Sulindac, polyp growth can be reduced in some FAP patients. In many cases, however, surgical treatment cannot be avoided as a result, especially in the case of a rapidly increasing polyp growth.
Polyps in the duodenum: the lifetime risk of adenomas occurring is 80–90%. Polyps in the duodenum usually do not cause any symptoms. Nevertheless, such adenomas - although not as common as in the large intestine - can become malignant as a result of growth in size in around 4–12% of FAP patients (duodenal cancer). Therefore, regular examinations (gastric and duodenal endoscopy) are strongly recommended.
Polyps in the stomach : these are mostly benign glandular cysts that do not require any further treatment (in around 30% of patients), gastric adenomas are less common (around 10%). The risk of gastric cancer in FAP patients is at most slightly increased (probably around 0.5% of those affected).
Desmoids: connective tissue tumors that arise mainly postoperatively in the abdominal wall or in the abdomen. Although they do not form metastases, they can, under certain circumstances, become very large and then have a displacing effect on other organs (in 10–30% of patients).
Pigment spots on the retina (congenital hypertrophy of the retinal pigment epithelium = CHRPE): harmless dark spots on the retina that can only be detected by an ophthalmologist and do not impair vision (in around 80% of patients with classic FAP).
Epidermoid cysts: benign growths under the skin that often appear in childhood (around 50% of patients).
Tooth anomalies: irregularities in the shape or number of teeth (in around 15–20% of patients).
Osteomas: benign bone tumors, especially of the jaw, face and skull (in 75–90% of patients).
Thyroid cancer: Papillary thyroid cancer probably occurs in around 2% of those affected, mostly between the ages of 15 and 30.
Medulloblastoma: This is a brain tumor that typically develops in the area of the posterior fossa in children or adolescents (probably in less than 1% of patients).
Hepatoblastoma: this is an embryonic tumor of the liver that occurs preferentially in the first five years of life (in about 1% of those affected).
Attenuated familial adenomatous polyposis (aFAP)
The aFAP is a special form of the FAP. It is a milder form in which the clinical symptoms do not develop as quickly. Mutations in the APC gene, but also in the MUTYH gene, are found to be the cause . In patients with aFAP, symptoms only appear on average from the age of 31. Polyps are also less present and are limited to a number of less than 100. These polyps are usually found in the ascending colon ( ascending colon ).
See also
literature
- Horst-Dieter Becker, Werner Hohenberger , Theodor Junginger, Peter Michael Schlag (eds.): Surgical oncology . Thieme, Stuttgart 2002, ISBN 3-13-126111-0 .
- EJ Gardner: A genetic and clinical study of intestinal polyposis, a predisposing factor for carcinoma of the colon and rectum. In: Am J Hum Genet. 1951; 3, pp. 167-176. PMID 14902760
- Polymnia Galiatsatos, William D. Foulkes: Familial Adenomatous Polyposis . In: American Journal of Gastroenterology . 2006, Am. Coll. of Gastroenterology, ISSN 0002-9270 , pp. 385-398.
- V. Fendrich, DK Bartsch: Hereditary gastrointestinal neoplasms . In: Z Gastroenterol. 2005; 43, pp. 219-225, Georg Thieme Verlag, Stuttgart / New York, ISSN 0044-2771
Individual evidence
- ↑ Wolfgang Piper: Internal medicine. Heidelberg 2007, p. 378.
- ↑ Gerd Herold: Internal medicine: a lecture-oriented presentation . 2012th edition. Herold, Cologne 2012, ISBN 978-3-9814660-1-0 .
- ↑ a b c Archive link ( Memento of the original from September 10, 2012 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice.
- ^ Rüdiger Siewert: Surgery. 8th edition. Heidelberg 2006, p. 619.
