Cowden Syndrome

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Classification according to ICD-10
Q85.8 Other phacomatoses, not elsewhere classified
ICD-10 online (WHO version 2019)

The Cowden syndrome , which in English as a disease Cowden or multiple hamartoma syndrome is called, is a pleomorphic , autosomal dominant inherited syndrome that clinically by hamartomas of all three germ layers makes its appearance. The cause is a mutation in the PTEN gene, which is why the syndrome is also included in the group of PTEN hamartoma tumor syndrome , as it is associated with the other syndromes in this group, such as Bannayan-Riley-Ruvalcaba syndrome or Proteus syndrome , numerous overlaps exist. These heterogeneous syndromes have a very variable and age-dependent penetrance and gene expression .

Epidemiology

The incidence is estimated to be less than 1: 200,000, the penetrance being age-dependent, but symptoms occurring in 90% of those affected by the age of 20. Both sexes are affected equally often. At least 150 cases of Cowden's syndrome are currently statistically recorded worldwide.

Pathophysiology

The mutation responsible is in the area of ​​the PTEN gene on the long arm of the 10th chromosome ( gene locus q23), where PTEN ( phosphatase and tensin homolog ) is a tumor suppressor gene . PTEN is an inhibitor of the protein kinase Akt , which is a central target molecule in the transduction of many important anti-apoptotic and proliferative signals and is overactive in the absence of PTEN inhibition due to mutation and thus promotes tumor development.

Clinical manifestation

In Cowden's syndrome, multiple hamartomas, including those of the skin and mucous membranes, almost always occur. The skin changes are pathognomonic , with trichilemmomas on the face, oral mucosal papillomas and acral or palmoplantar keratoses as well as multiple facial papules and macular pigmentation of the penis being particularly common . There are also often numerous gastrointestinal hamartomas and ganglioneuromas .

Other benign tumors in other organs are also often found in the presence of Cowden's syndrome, such as thyroid nodules , fibrocystic breast changes, fibromas and lipomas of the connective tissue, and uterine fibroids (connective tissue uterine tumors that consist of smooth muscle cells. See uterine myoma and leiomyoma ).

An oversized head circumference ( macrocephaly ) is still very typical .

In addition, the risk of cancer is significantly increased. Breast cancer , uterine cancer and non-medullary thyroid cancer occurring at a young age are observed particularly often , and renal cell carcinoma is also more common.

In addition, a mental handicap or disorders from the autistic group are often observed.

The clinical diagnosis is made using a combination of so-called major and minor criteria based on a guideline of the American National Comprehensive Cancer Network . If these criteria are met, a genetic test for the presence of a PTEN mutation should be performed.

treatment

Only symptomatic treatment can be carried out, which includes a control of all abnormalities for degeneration and, if necessary, surgical removal and further therapy.

forecast

According to a 2010 study with 211 test persons, 89% of all patients developed at least one malignant tumor by the age of 70 . The probability of occurrence of colorectal cancer in this time window was around 15% and that of endometrial cancer was 21%. The risk of breast cancer is also significantly increased in women . Fewer malignant tumors were diagnosed in male patients compared to female patients.

Web links

Individual evidence

  1. Erik K. Alexander, Gayun Chan-Smutko, Mansi A. Saksena, Ion Popa: Case 19-2013 - A 35-Year-Old Woman with Recurrent Goiter and Ductal Carcinoma of the Breast. In: New England Journal of Medicine 2013; Volume 368, Issue 25 of June 20, 2013, pages 2416-2424; doi : 10.1056 / NEJMcpc1209273
  2. Lois Jovanovic, Genell J. Subak-Sharpe: Hormones. The medical manual for women. (Original edition: Hormones. The Woman's Answerbook. Atheneum, New York 1987) From the American by Margaret Auer, Kabel, Hamburg 1989, ISBN 3-8225-0100-X , p. 374.
  3. DL. Riegert-Johnson, FC Gleeson, M Roberts, K Tholen, L Youngborg, M Bullock, LA Boardman: Cancer and Lhermitte-Duclos disease are common in Cowden syndrome patients . In: Hereditary Cancers in Clinical Practice . No. 1, 2010, p. 6. doi : 10.1186 / 1897-4287-8-6 . PMID 20565722 . PMC 2904729 (free full text).