Bannayan-Riley-Ruvalcaba Syndrome (BRRS)

What is Bannayan-Riley-Ruvalcaba syndrome?

Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a genetic disorder that increases your risk of getting tumors. It’s part of a group of conditions called PTEN hamartoma tumor syndrome (PHTS). PHTS includes both Cowden syndrome and BRRS.

BRRS usually happens when there’s a mutation (change) in your PTEN gene. Your PTEN gene produces proteins that slow the growth of tumors. Because people with BRRS have a damaged PTEN gene, many develop hamartomas (tumor-like growths) and other noncancerous and cancerous tumors. They also have an increased risk of developing cancers. Other symptoms may include high birth weight, macrocephaly (large head), freckles on your penis, and various developmental and intellectual delays.

Other names for Bannayan-Riley-Ruvalcaba syndrome include:

• Riley-Smith syndrome.
• Ruvalcaba-Myhre syndrome.
• Ruvalcaba-Myhre-Smith syndrome.
• Bannayan-Zonana syndrome.

How common is BRRS?

Experts don’t know exactly how many people have BRRS because symptoms vary widely and some are subtle. But most researchers believe the condition is rare.

What are the symptoms of BRRS?

Bannayan-Riley-Ruvalcaba syndrome symptoms vary significantly and may include:

• High birth weight and length.
• Macrocephaly (large head).
• Pigmented macules (freckles) on your penis.
• Low muscle tone (hypotonia).
• Developmental delays in speech and/or motor skills.
• Intellectual disabilities (about 50% of people with BRRS).
• Autism spectrum disorder (up to 20% of children diagnosed with autism spectrum disorder have a mutation in their PTEN gene).
• Muscle weakness.
• Hamartomas (noncancerous growths made of abnormal cells and tissues) in your intestinal tract.
• Hyperflexible joints.
• Seizures.
• Pectus excavatum (a condition in which your breastbone sinks into your chest).
• Scoliosis.
• Acanthosis nigricans (dark discoloration in your body’s folds and creases).
• Lipomas (fatty tumors located just beneath your skin).
• Angiolipomas (noncancerous growths made of fat and blood vessels).
• Hemangiomas (birthmarks made of extra blood vessels under your skin).

What causes BRRS?

BRRS can occur for two reasons:

1. There’s a mutation in your PTEN gene. (This is the most common cause.)
2. There’s a large deletion of genetic material that includes all or part of your PTEN gene. (This occurs in about 10% of cases.)

Your PTEN gene produces a protein that slows the growth of tumors. When this gene is missing or not working properly, your cells can divide uncontrollably, resulting in the development of hamartomas and other cancerous and noncancerous tumors.

Experts have yet to determine why PTEN gene mutations cause other BRRS symptoms, such as macrocephaly, muscular and skeletal abnormalities, and developmental and intellectual delays.

How is BRRS inherited?

Parents can pass BRRS to their biological children through autosomal dominant inheritance. This means that if one parent has one copy of the mutated PTEN gene, then their child has a 50% chance of inheriting the condition.

How is BRRS diagnosed?

If a healthcare provider suspects that you could have BRRS, they’ll likely recommend genetic testing of the PTEN gene. Your provider will use gene sequencing — a process that examines each component of the gene for changes or mutations.

PTEN testing is accurate. If your provider finds a PTEN gene mutation, then they can confirm your BRRS diagnosis with 100% certainty. But only 60% of people with BRRS symptoms have an identifiable gene mutation. This means that up to 40% of people with BRRS symptoms will receive a normal test result. If you’re interested in PTEN testing, talk to your healthcare provider.

How is BRRS treated?

There’s no specific treatment for BRRS. Rather, Bannayan-Riley-Ruvalcaba syndrome treatment involves managing the signs and symptoms that are unique to you.

People with BRRS should have routine monitoring for various types of cancers, whether they have BRRS symptoms or not. Healthcare providers recommend that people who have a documented PTEN gene mutation follow the screening guidelines for Cowden syndrome. This includes screenings for:

• Breast cancer.
• Uterine cancer.
• Thyroid cancer.
• Kidney cancer.

Genetic counseling is beneficial for people with BRRS. Family members who don’t show BRRS symptoms should have PTEN gene testing to determine if they also need to follow cancer screening guidelines.

Surveillance guidelines for BRRS

For each cancer type, there are specific surveillance guidelines, including when to start screening. Screening doesn’t start at the time of diagnosis for all cancers — and it depends on the person’s age at diagnosis.

For people under the age of 18, healthcare providers may recommend:

• Yearly thyroid ultrasound starting at age 7.
• Yearly skin check with physical examination.
• Neurodevelopmental evaluation.
• Yearly hemoglobin test for early detection of intestinal hamartomas.

Can you prevent BRRS?

No, you can’t prevent BRRS because it’s a genetic condition that results from a gene mutation. People who have BRRS can get genetic counseling to help them make informed decisions about healthcare and having biological children.

What can I expect if I have BRRS?

The outlook for BRRS varies greatly from person to person. Some people may have several signs and symptoms — others may have few or none at all. There are many management options available that can help people with BRRS improve their overall quality of life, including physical and speech therapy.

As mentioned above, people with BRRS should have regular screenings to check for various types of cancer. Ask your healthcare provider when you should start screenings and how often you should have them.

Bannayan-Riley-Ruvalcaba syndrome life expectancy

Researchers have yet to discover an average life expectancy for people with BRRS. In fact, there’s no evidence to suggest that people with BRRS have a reduced life expectancy. However, people with BRRS have a higher risk of certain cancers at a younger age. For this reason, some people could have cancer-related reduced life expectancy.

When should I see my healthcare provider?

If you have immediate family members with BRRS (such as biological siblings, parents or children), then you should ask your healthcare provider about PTEN genetic testing. PTEN testing can tell you if you have a PTEN gene mutation and whether you should have regular screenings for certain cancers.

If you or your child received a BRRS diagnosis, your healthcare provider will work with you to manage symptoms and improve quality of life. They’ll also tell you how often you should have preventive cancer screenings.

What questions should I ask my doctor?

If you or a loved one received a BRRS diagnosis, here are some questions you may want to ask your healthcare provider:

• Do I have, or does my child have, an identifiable PTEN gene mutation?
• Are there obvious signs and symptoms?
• Should I undergo genetic testing?
• Should my immediate family members undergo genetic testing?
• How does this impact family planning?
• What treatments or management options do you recommend?
• How often should I have preventive cancer screenings?

A note from Cleveland Clinic

Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a rare genetic condition that results from a mutation in your PTEN gene. Symptoms vary widely and can range from mild to severe. There’s no specific treatment for BRRS. Instead, treatment focuses on managing your underlying conditions. People with BRRS should have routine screenings for certain types of cancer, including breast, uterine, thyroid and kidney cancers. Talking with a counselor or social worker can help you work through the emotions that can accompany a BRRS diagnosis. You may also wish to join a local or online support group to meet others who share your experience.