The information on this page was reviewed and approved by
Maurie Markman, MD, President, Medicine & Science at CTCA.

This page was updated on June 28, 2021.

Cowden syndrome

Cowden syndrome (CS), also known as Cowden’s disease and multiple hamartoma syndrome, is a rare inherited disorder that causes benign, or noncancerous, growths in various places on the body. The growths, called hamartomas, typically start to appear when patients reach their late 20s. However, they may appear at any time between birth and your mid-40s.

The growths are most likely to develop on the outer sheath of hair follicles and in the mouth. Hamartomas also may be found along the inner lining of the gastrointestinal tract.

While the tumors are benign, this syndrome increases the risk of developing certain types of cancer, including:

Women with CS are at greatest risk of developing breast cancer. The risk may be as high as 85 percent, according to the American Society of Clinical Oncology (ASCO). Women with CS may develop breast cancer at a younger age compared with other women. Women also are at risk of developing cancer in a second breast if they have cancer in the other. Men with CS are at some risk for developing breast cancer as well.

According to ASCO, other risks for people with CS include:

  • Thyroid cancer: 30-40 percent
  • Kidney cancer: 30-35 percent
  • Endometrial cancer in women: 25-30 percent
  • Colorectal cancer: 5-10 percent
  • Melanoma: 6 percent

People with CS also have been known to develop other types of cancers, including:

However, it’s not known if there’s a link between CS and the risk for these other cancers.

Signs and symptoms

People with CS may have:

  • Skin tags
  • Flesh-colored papules around the eyes, nose and mouth
  • Wart-like papules on the back of the hands and feet

Other signs and symptoms of CS include:

  • Enlarged head (macrocephaly)
  • Autism spectrum disorder
  • Abnormalities of the vascular system
  • Benign diseases of the breast, thyroid and endometrium
  • Lhermitte-Duclos (rare, benign brain tumor)

Causes of CS

Cowden syndrome is a genetic disorder, meaning that it’s caused by a gene mutation. Most often, the mutation occurs in the PTEN (phosphatase and tensin homolog) gene that regulates cell growth. When mutated, PTEN is unable to suppress tumor growth, and lots of benign tumors that could turn cancerous begin to form.

Most cells have two copies of every gene—one from each parent. However, CS is autosomal dominant, meaning it takes only one gene mutation from either parent to cause the disease in offspring. A parent with CS has a 50 percent chance of passing along the mutated gene to the child with each pregnancy, according to the Genetic and Rare Diseases Information Center.

In rare instances, CS may result from mutations in other genes, including:

  • KLLN
  • SDHB
  • SDHC
  • SDHD
  • PIK3CA
  • AKT1

Some people may have CS and not know which gene, if any, caused it. Some may develop CS from a new, random mutation. The cause of CS in these people isn’t known. No one in the family may have a history of the disease.

How common is CS?

Men and women inherit this disorder in equal numbers. Although rare, CS is estimated to affect one in every 200,000 people, according to ASCO.

How is CS diagnosed?

Cowden syndrome may be difficult to diagnose. Many experts—such as oncologists, geneticists, genetic counselors and nurses who are certified in hereditary cancer—have devised a list of characteristics (major and minor criteria) that may suggest CS. These criteria continue to evolve as new information comes to light.

The criteria are divided into three groups:

  1. Mucosal and skin lesions
  2. Cancers
  3. Other malformations

The major criteria include:

  • Breast, endometrial and/or follicular thyroid cancer
  • Macrocephaly
  • Multiple benign tumors of the gastrointestinal tract, or ganglioneuromas
  • Discolored area on the skin of the head of the penis
  • Multiple wart-like projections on the face
  • Abnormal thickening of the hands and feet
  • Extensive mucosal papillomatosis in the oral cavity
  • Biopsy-confirmed benign tumor of the outer sheath of the hair follicle
  • Mucocutaneous lesions

The minor criteria include:

  • Colon cancer
  • Autism spectrum disorder
  • Mental retardation
  • A variant of thyroid cancer
  • Thyroid lesions, such as adenoma or goiter
  • Kidney cancer
  • Vascular anomalies
  • Benign soft-tissue tumors (lipomas)
  • Glycogenic acanthosis (benign thickening of the esophageal squamous epithelium
  • A gastrointestinal hamartoma or ganglioneuroma
  • A testicular disorder known as lipomatosis

The number of major and minor criteria patients exhibit determines a diagnosis. For example, adult patients who have two or more major criteria, one major and three or more minor criteria, or four or more minor criteria are likely to be diagnosed with CS.

After this initial diagnosis, the patient may undergo genetic testing for confirmation. A blood test is used to determine whether the person has a PTEN gene mutation. The diagnosis is confirmed if a mutation in the PTEN or other causal genes is found.

Some people may have a PTEN gene mutation but none of the criteria for CS. It’s unclear whether the person would face the same risks for developing cancer in this case.

Cancer screening

Because Cowden syndrome greatly increases the risk of developing different cancers, it’s important to adhere to strict screening for early detection.

It’s recommended women with CS undergo:

  • Breast self-exam starting at age 18
  • Clinician-performed breast exams every six to 12 months starting at age 25
  • Annual mammograms starting at age 30-35; annual magnetic resonance imaging (MRI) screening as well

Some women may opt to have prophylactic surgery (removing healthy organs) to prevent the possibility of developing breast, uterine or other cancers.

Men and women with Cowden syndrome in the family should have:

  • Annual physical exam starting at age 18
  • Annual thyroid ultrasound starting at age 18
  • Baseline colonoscopy starting at age 35. Follow-ups should be at least every five years. If polyps are found, follow-ups may be needed more frequently.
  • Kidney ultrasound every one to two years starting at age 40

If close family members are diagnosed with Cowden syndrome, doctor and patient should determine the best screening schedule.

Children in families with Cowden syndrome should have:

  • Yearly thyroid ultrasound if a PTEN pathogenic variant is found
  • Yearly skin checks as part of physical exams
  • Neurodevelopmental evaluations

Biopsies may be needed to diagnose skin lesions from CS. If the person shows no symptoms, it’s fine to rely on observation. However, if any lesions are suspicious or cause pain or scarring, you should discuss ways to have them removed.

Those with a history of malignancies in the family should be sure to discuss their family history with their providers.

Treating skin lesions

Not much may be done to control skin lesions that are common in Cowden syndrome. Some doctors prescribe topical treatments, though these haven’t been shown to provide much improvement. Some patients have seen improvements with systemic retinoids.

Facial lesions may be treated with:

  • Chemical peels
  • Dermabrasion
  • Laser resurfacing

Surgery to remove the benign tumors is possible, but it must be done with care because scarring may occur, and the lesions may return.

Because people with CS are at increased risk for melanoma, it’s important to take preventive measures, such as wearing sunscreen and protective clothing, when in the sun starting as a child. It’s also critical to avoid blistering burns, especially before age 20.

Clinical trials are underway to look at new treatments, including Sirolimus (rapamycin), a type of immunosuppressant and antibiotic.

Cancer screenings and follow-ups are key for those with CS. Patients should look for providers who specialize inCowden syndrome and can help sort out the challenges and options for detecting cancer early.

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