Cowden Syndrome

What causes Cowden syndrome

The PTEN gene makes a tumor suppressor protein that tells cells when to stop growing. People with Cowden syndrome inherit one faulty copy. When the working copy is also damaged in a cell, that cell can grow uncontrollably, forming hamartomas (disorganized benign growths) or cancers.

Cowden syndrome is part of the PTEN hamartoma tumor syndrome (PHTS) spectrum, which also includes Bannayan-Riley-Ruvalcaba syndrome and some PTEN-related autism. About 10 to 45 percent of cases are new (de novo) changes not inherited from a parent.

Signs and symptoms

Skin and mouth (present in most adults)

• trichilemmomas: small, skin-colored bumps on the face, often around the nose, mouth and ears
• papillomatous papules: small, smooth bumps on the gums, lips and tongue, giving a cobblestone appearance
• acral keratoses: small, rough bumps on the hands and feet
• lipomas (fatty lumps) and vascular malformations

Head size

Macrocephaly (a large head) is found in most people with Cowden syndrome.

Benign growths in organs

• thyroid nodules, goiter and Hashimoto's thyroiditis
• fibrocystic breast changes and fibroadenomas
• hamartomatous polyps throughout the gut, including the esophagus
• uterine fibroids
• Lhermitte-Duclos disease: a rare, slow-growing benign tumor of the cerebellum

Development

Some children with PTEN changes have developmental delay, learning difficulties or autism spectrum disorder. Children with autism and a very large head may be offered PTEN testing.

Cancer risks

Estimated lifetime risks vary between studies:

Men also have a raised breast cancer risk, though it remains low in absolute terms. Cancers tend to occur at younger ages than usual.

Diagnosis

Doctors use clinical criteria (major and minor features, such as macrocephaly, breast or thyroid cancer, multiple gut hamartomas, characteristic skin findings) to decide who should be tested. The diagnosis is confirmed by genetic testing of PTEN in a blood or saliva sample. Once a variant is found, relatives can be tested for that specific change.

Genetic counseling before and after testing explains results, implications for family members and options for pregnancy planning.

Screening and management

Screening recommendations (from NCCN guidance) usually include:

• from diagnosis (childhood): yearly physical exam; thyroid ultrasound yearly starting at age 7
• breast (women): breast awareness from 18, clinical breast exam every 6 to 12 months from 25, yearly mammogram and breast MRI from 30 to 35 (or earlier based on family history)
• endometrial: education about abnormal bleeding; some women choose yearly endometrial sampling from 35
• colorectal: colonoscopy starting at 35, repeated every 5 years or more often if polyps are found
• kidney: imaging (ultrasound or MRI) every 1 to 2 years from 40
• skin: yearly dermatology review
• development: assessment in children

Risk-reducing surgery

Some women choose risk-reducing mastectomy, and hysterectomy after childbearing, to lower cancer risk. These are personal decisions made with specialist counseling.

Treatment

Skin lesions can be removed if bothersome. Cancers are treated in the usual way, with surgery, radiation or other therapies, often by teams familiar with hereditary cancer. Research into drugs that target the PTEN pathway (mTOR inhibitors) is ongoing.

Outlook

With regular screening, cancers are often found early, when they are most treatable. Many people with Cowden syndrome live long lives. Awareness of the syndrome among family members allows them to be tested and screened too.

Frequently asked questions

What are the signs of Cowden syndrome?

Common signs include a large head, small skin-colored bumps on the face, cobblestone-like bumps in the mouth, rough bumps on the hands and feet, and benign growths in the thyroid, breast, uterus and gut. Some children have developmental delay or autism.

What cancers are linked to Cowden syndrome?

Cowden syndrome raises the lifetime risk of breast, thyroid (usually follicular), endometrial, kidney and colorectal cancer and melanoma. Cancers often occur at younger ages, which is why screening starts earlier than for the general population.

Is Cowden syndrome inherited?

Yes. It is autosomal dominant, so a person with Cowden syndrome has a 50 percent chance of passing the PTEN variant to each child. Some people have a new variant that was not inherited from either parent.

How is Cowden syndrome diagnosed?

Doctors look for characteristic features using clinical criteria, then confirm the diagnosis with genetic testing for a PTEN variant. Once a family variant is known, relatives can be tested specifically for it.

What screening is recommended for Cowden syndrome?

Typical screening includes yearly exams, thyroid ultrasound from childhood, breast MRI and mammograms from about 30, colonoscopy from 35, kidney imaging from 40, skin checks, and attention to abnormal uterine bleeding. Your genetics team tailors the plan.