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Diseases

Genetic and Rare Diseases Information Center (GARD)

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Cowden syndrome


Other Names for this Disease

  • CD
  • Cowden disease
  • Cowden's disease
  • CS
  • MHAM
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Cause

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What causes Cowden syndrome?

Changes involving at least four genes, PTEN, SDHB, SDHD, and KLLN, have been identified in people with Cowden syndrome or Cowden-like syndrome. 

Most cases of Cowden syndrome and a small percentage of cases of Cowden-like syndrome result from mutations in the PTEN gene.  PTEN is a tumor suppressor gene, which means that it normally prevents cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in the PTEN gene have been identified in about 85 percent of people with Cowden syndrome. These mutations, which affect all of the body's cells, prevent the PTEN protein from effectively regulating cell survival and division. Uncontrolled cell division can lead to the formation of hamartomas and cancerous tumors.

Other cases of Cowden syndrome and Cowden-like syndrome result from changes involving the KLLN gene. This gene provides instructions for making a protein called killin. Like the protein produced from the PTEN gene, killin probably acts as a tumor suppressor. The genetic change that causes Cowden syndrome and Cowden-like syndrome is known as promoter hypermethylation. The promoter is a region of DNA near the gene that controls gene activity (expression). Hypermethylation occurs when too many small molecules called methyl groups are attached to the promoter region. The extra methyl groups reduce the expression of the KLLN gene, which means that less killin is produced. A reduced amount of killin may allow abnormal cells to survive and proliferate inappropriately, which can lead to the formation of tumors.

A small percentage of people with Cowden syndrome or Cowden-like syndrome have variations in the SDHB or SDHD gene. These genes provide instructions for making parts of an enzyme called succinate dehydrogenase (SDH), which is important for energy production in the cell. This enzyme also plays a role in signaling pathways that regulate cell survival and proliferation. Variations in the SDHB or SDHD gene alter the function of the SDH enzyme. Studies suggest that the defective enzyme may allow cells to grow and divide unchecked, leading to the formation of hamartomas and cancerous tumors. However, researchers are uncertain whether the identified SDHB and SDHD gene variants are directly associated with Cowden syndrome and Cowden-like syndrome. Some of the variants described above have also been identified in people without the features of these conditions.

When Cowden syndrome and Cowden-like syndrome are not related to changes in the PTEN, SDHB, SDHD, or KLLN genes, the cause of the conditions is unknown. [1]

Last updated: 10/23/2012

References
  1. Cowden syndrome. Genetics Home Reference (GHR). March 2006; http://ghr.nlm.nih.gov/condition=cowdensyndrome. Accessed 5/18/2011.


Other Names for this Disease
  • CD
  • Cowden disease
  • Cowden's disease
  • CS
  • MHAM
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.