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PTEN hamartoma tumor syndrome, including Cowden syndrome

Peter P Stanich, MD
Noralane M Lindor, MD
Section Editors
J Thomas Lamont, MD
Benjamin A Raby, MD, MPH
Carolyn Bridgemohan, MD
Deputy Editor
Diane MF Savarese, MD


Germline mutations in the phosphatase and tensin homolog (PTEN) gene have been described in a variety of rare syndromes that are collectively known as PTEN hamartoma tumor syndromes (PHTS). The defining clinical feature of PHTS is the presence of hamartomatous tumors, which are disorganized growths of native cells in native tissues.

The phenotypic spectrum of PHTS includes the following entities:

Cowden syndrome (also known as Cowden disease or multiple hamartoma syndrome) is the best-described PHTS. It is inherited in an autosomal dominant fashion. Besides multiple hamartomas in a variety of tissues, patients have characteristic dermatologic manifestations such as trichilemmomas, oral fibromas, and punctate palmoplantar keratoses, and an increased risk of breast, endometrial, thyroid, kidney and colorectal cancers.

Bannayan-Riley-Ruvalcaba syndrome is another rare PHTS inherited in an autosomal dominant fashion. In addition to hamartomas, these patients have multiple subcutaneous lipomas, macrocephaly, and penile lentigines (picture 1). High penetrance of cancer, as seen in Cowden syndrome, has not been clearly documented.

Genotype analyses have concluded that a similar mutation spectrum in the PTEN gene is found in both Cowden and Bannayan-Riley-Ruvalcaba syndromes, leading to the conclusion that they are related allelic disorders [1-3]. Both conditions are now considered phenotypically distinct, age-related presentations of a similar genetic abnormality [4,5].

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Literature review current through: Nov 2017. | This topic last updated: Aug 23, 2016.
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