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Genetic and Rare Diseases Information Center (GARD)

Cowden syndrome

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

Your Question

My physician recently mentioned that I may be at risk for Cowden syndrome. What can you tell me about this condition? 

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

What is Cowden syndrome?

Cowden syndrome is an inherited condition that is characterized primarily by multiple, noncancerous growths (called hamartomas) on various parts of the body. It is considered part of the PTEN Hamartoma Tumor Syndrome spectrum which also includes Bannayan-Riley-Ruvalcaba syndrome and Proteus syndrome. People affected by Cowden syndrome are also at an increased risk of developing certain types of cancer, such as breast, thyroid and endometrial (lining of the uterus) cancer. Most cases are caused by changes (mutations) in the PTEN gene and are inherited in an autosomal dominant manner.[1][2] Management typically includes high-risk screening for associated tumors and/or prophylactic surgeries.[3]
Last updated: 3/15/2015

What symptoms are associated with Cowden sydnrome?

Cowden syndrome is characterized primarily by multiple, noncancerous growths (called hamartomas) on various parts of the body. Approximately 99% of people affected by Cowden syndrome will have benign growths on the skin and/or in the mouth by the third decade of life. A majority of affected people will also develop growths (called hamartomatous polyps) along the inner lining of the gastrointestinal tract.[1][2]

People affected by Cowden syndrome also have an increased risk of developing certain types of cancer. Breast, thyroid and endometrial (the lining of the uterus) cancers are among the most commonly reported tumors. Other associated cancers include colorectal cancer, kidney cancer and melanoma. People with Cowden syndrome often develop cancers at earlier ages (before age 50) than people without a hereditary predisposition to cancer.[3][1]

Other signs and symptoms of Cowden syndrome may include benign diseases of the breast, thyroid, and endometrium; a rare, noncancerous brain tumor called Lhermitte-Duclos disease; an enlarged head (macrocephaly); autism spectrum disorder; intellectual disability; and vascular (the body's network of blood vessels) abnormalities.[3][1]
Last updated: 3/16/2015

What causes Cowden syndrome?

Most cases of Cowden syndrome are caused by changes (mutations) in the PTEN gene. PTEN is a tumor suppressor gene which means that it encodes a protein that helps keep cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in PTEN result in a defective protein that is unable to carry out its normal role. This leads to the development of the various tumors and cancers associated with Cowden syndrome.[1]

Rarely, Cowden syndrome is caused by mutations in KLLN, SDHB, SDHC, SDHD, PIK3CA or AKT1. Some affected families have no identifiable mutation in any of the genes associated with Cowden syndrome; in these families, the exact underlying cause is unknown.[1][4][5]
Last updated: 3/16/2015

Is genetic testing available for Cowden syndrome?

Yes, genetic testing is available for many of the genes known to cause Cowden syndrome.[1] Carrier testing for at-risk relatives and prenatal testing are possible if the disease-causing mutation in the family is known.

The Genetic Testing Registry (GTR) is a centralized online resource for information about genetic tests. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Last updated: 3/16/2015

How is Cowden syndrome diagnosed?

A diagnosis of Cowden syndrome is based on the presence of characteristic signs and symptoms. Genetic testing for a change (mutation) in the PTEN gene can then be ordered to confirm the diagnosis. If a mutation in PTEN is not identified, genetic testing for the other genes known to cause Cowden syndrome can be considered.[1]

GeneReviews offers more detailed information regarding the diagnosis of Cowden syndrome including the clinical diagnostic criteria. Click here to view this resource.

The PTEN Cleveland Clinic Risk Calculator can be used to estimate the chance of finding a PTEN mutation in children and adults with signs and symptoms of Cowden syndrome.
Last updated: 3/16/2015

How is Cowden syndrome inherited?

Cowden syndrome is inherited in an autosomal dominant manner.[1] This means that to be affected, a person only needs a change (mutation) in one copy of the responsible gene in each cell. In some cases, an affected person inherits the mutation from an affected parent. Other cases may result from new (de novo) mutations in the gene. These cases occur in people with no history of the disorder in their family. A person with Cowden syndrome has a 50% chance with each pregnancy of passing along the altered gene to his or her child.
Last updated: 3/16/2015

How can I find a genetics professional in my area?

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.
Last updated: 7/15/2016

How might Cowden syndrome be treated?

Because Cowden syndrome is associated with an increased risk for certain types of cancer, management is typically focused on high-risk cancer screening. According to the National Comprehensive Cancer Network 2014, the recommended screening protocol for Cowden syndrome includes:[3]

Cancer Screening for Women
  • Breast self exams beginning at age 18
  • Clinical breast exams every 6-12 months beginning at age 25**
  • Annual mammogram and breast MRI beginning at age 30-35**
  • Annual screening for endometrial cancer with ultrasound and/or random biopsy may be considered beginning at age 30-35
  • Prophylactic surgeries may be considered as a preventative option for some forms of cancer
Cancer Screening for Men and Women
  • Annual physical examination beginning at age 18**
  • Annual thyroid ultrasound beginning at age 18**
  • Baseline colonoscopy at age 35 with follow-up every 5 years (more frequent if polyps identified)
  • Consider renal (kidney) ultrasound every 1-2 years beginning at age 40

**or individualized based on the earliest diagnosis of cancer in the family

GeneReviews offers more specific information on the treatment and management of Cowden syndrome. To access this resource, please click here.
Last updated: 3/16/2015

  • Charis Eng, MD, PhD. PTEN Hamartoma Tumor Syndrome (PHTS). GeneReviews. January 2014;
  • Katherine H Fiala, MD. Cowden Disease (Multiple Hamartoma Syndrome). Medscape Reference. February 2014;
  • Mary B. Daly, MD, PhD; Robert Pilarski, MS, CGC. Genetic/Familial High-Risk Assessment: Breast and Ovarian. National Comprehensive Cancer Network. February 2014; Accessed 3/10/2015.
  • Ni Y, He X, Chen J, Moline J, Mester J, Orloff MS, Ringel MD, Eng C. Germline SDHx variants modify breast and thyroid cancer risks in Cowden and Cowden-like syndrome via FAD/NAD-dependant destabilization of p53. Hum Mol Genet. January 2012; 21(2):300-310.
  • Orloff MS, He X, Peterson C, Chen F, Chen JL, Mester JL, Eng C. Germline PIK3CA and AKT1 mutations in Cowden and Cowden-like syndromes. Am J Hum Genet. January 2013; 92(1):76-80.
Other Names for this Disease
  • Cowden disease
  • CD
  • Cowden's disease
  • CS
  • Multiple hamartoma syndrome
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.