What Is Bannayan-Riley-Ruvalcaba Syndrome? Symptoms, Causes, and Care
Updated: 2 days ago
Medically reviewed by Dr. Baraa Alnahhal, MD · Last reviewed: October 2026
Quick Answer: What is Bannayan-Riley-Ruvalcaba syndrome (BRRS)?
Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a rare genetic condition caused by a change in the PTEN tumor suppressor gene, letting cells divide uncontrollably and form hamartomas and other tumors. [1] [3] It is autosomal dominant, so an affected parent's child has a 50% chance of inheriting it. [1] [4] Diagnosis uses PTEN gene testing, and management includes lifetime cancer surveillance. [1]
Key takeaways
BRRS is a rare genetic disorder that increases your risk of tumors and is part of PTEN hamartoma tumor syndrome (PHTS). [1]
It's usually caused by a mutation in the PTEN gene, which normally slows tumor growth. [1]
Symptoms vary widely: large head, high birth weight, low muscle tone, developmental delays, and tumor-like growths. [1] [3]
It's inherited in an autosomal dominant pattern: each child of a parent with the mutation has a 50% chance. [1]
PTEN gene testing can confirm BRRS with 100% certainty, but only about 60% of symptomatic people have an identifiable mutation. [1]
There's no specific treatment: care means managing symptoms and routine cancer screening. [1]
Experts have not found evidence of a reduced life expectancy from BRRS itself. [1]
What the research says
Cancer risk in PTEN hamartoma tumor syndrome (which includes BRRS) is high, but estimates vary. A review of nine cohort studies from four independent PHTS cohorts found reported lifetime risks of any cancer between 81% and 90%. By cancer type, breast cancer risk (women, by age 60 to 70) ranged from 67% to 85%, endometrial cancer 19% to 28%, thyroid cancer 6% to 38%, and kidney cancer 2% to 24%. The authors urge caution because the studies were mostly retrospective, focused on index cases, and included little pediatric data. (Hendricks et al., Clin Genet, 2021) [6]
Thyroid cancer in children with PHTS is real but uncommon, and the best age to start screening is still debated. In 81 children and teens with PHTS, thyroid cancer was found in 7.4% (6 of 81), all older than 10. Among children under 10 who had a thyroid ultrasound, 71.4% (15 of 21) had a normal scan, and the authors concluded ultrasound could wait until age 10 when the physical exam is normal. Because guidelines differ (the guidance above mentions age 7), follow the schedule your care team sets. (Baran et al., Horm Res Paediatr, 2020) [7]
A large head plus developmental concerns is the strongest clue for PTEN testing. Among 114 children tested for PTEN because of autism spectrum disorder (60), developmental delay or intellectual disability (49), or macrocephaly alone (5), 11 mutations were found: 8.3% of the autism group and 12.2% of the developmental delay group. Every child with a mutation had significant macrocephaly (more than 2 standard deviations above average). (Varga et al., Genet Med, 2009) [8]
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), which includes both Cowden syndrome and BRRS. [1]
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. [1] They also have an increased risk of developing cancers. [6]
Other symptoms may include high birth weight, macrocephaly (large head), freckles on the penis, and various developmental and intellectual delays. [3]
You may also see BRRS called Riley-Smith syndrome, Ruvalcaba-Myhre syndrome, Ruvalcaba-Myhre-Smith syndrome, or Bannayan-Zonana syndrome. [1]
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. [1]
What Are the Symptoms of BRRS?
BRRS symptoms vary significantly. Signs may include:
Symptom | Description |
High birth weight and length | Babies are born larger than typical |
Macrocephaly | A larger-than-typical head |
Pigmented macules | Freckles on the penis |
Low muscle tone | Weak muscle tension, called hypotonia |
Developmental delays | Delays in speech and/or motor skills |
Intellectual disabilities | Occur in about 50% of people with BRRS |
Autism spectrum disorder | Up to about 1 in 5 children with autism and a very large head have a PTEN gene mutation; it is uncommon in autism overall |
Muscle weakness | Reduced muscle strength |
Intestinal hamartomas | Noncancerous growths made of abnormal cells and tissues in the intestinal tract |
Hyperflexible joints | Joints that bend beyond the typical range |
Seizures | Abnormal electrical activity in the brain |
Pectus excavatum | A condition in which the breastbone sinks into the chest |
Scoliosis | Curving of the spine |
Acanthosis nigricans | Dark discoloration in the body's folds and creases |
Lipomas | Fatty tumors located just beneath the skin |
Angiolipomas | Noncancerous growths made of fat and blood vessels |
Hemangiomas | Birthmarks made of extra blood vessels under the skin |
What Causes BRRS?
BRRS can occur for two reasons:
Cause | Details |
PTEN gene mutation | A mutation (change) in your PTEN gene; this is the most common cause |
PTEN gene deletion | 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. [1]
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. [1]
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. [1] [4]
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. [1]
Diagnostic detail | What it means |
Test accuracy | PTEN testing is accurate: if your provider finds a PTEN gene mutation, they can confirm your BRRS diagnosis with 100% certainty |
Identifiable mutations | Only 60% of people with BRRS symptoms have an identifiable gene mutation |
Normal results | This means that up to 40% of people with BRRS symptoms will receive a normal test result |
Next step | If you're interested in PTEN testing, talk to your healthcare provider |
How Is BRRS Treated?
There's no specific treatment for BRRS. [1] Rather, BRRS treatment involves managing the signs and symptoms that are unique to you. [1]
Routine cancer screening
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. [1] This includes screenings for:
Cancer type | Part of routine surveillance |
Breast cancer | Yes |
Uterine cancer | Yes |
Thyroid cancer | Yes |
Kidney cancer | Yes |
Genetic counseling is beneficial for people with BRRS. [1] Family members who don't show BRRS symptoms should have PTEN gene testing to determine if they also need to follow cancer screening guidelines. [1]
Surveillance guidelines for children
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. [1] For people under the age of 18, healthcare providers may recommend:
Screening (under 18) | Details |
Thyroid ultrasound | Yearly, starting at age 7 |
Skin check | Yearly, with physical examination |
Neurodevelopmental evaluation | To track speech, motor, and cognitive development |
Hemoglobin test | Yearly, for early detection of intestinal hamartomas |
What Can I Expect If I Have BRRS?
The outlook for BRRS varies greatly from person to person. [1] Some people may have several signs and symptoms; others may have few or none at all. [1]
There are many management options available that can help people with BRRS improve their overall quality of life, including physical and speech therapy. [1] As noted 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.
What is the 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. [1] 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. [1]
Can BRRS Be Prevented?
No, you can't prevent BRRS because it's a genetic condition that results from a gene mutation. [1] People who have BRRS can get genetic counseling to help them make informed decisions about healthcare and having biological children. [1]
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. [1]
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.
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. [1]
Questions to ask your healthcare provider
Question | Why it helps |
Do I have, or does my child have, an identifiable PTEN gene mutation? | Confirms the genetic basis of the diagnosis |
Are there obvious signs and symptoms? | Clarifies what to watch for |
Should I undergo genetic testing? | Determines next steps for you |
Should my immediate family members undergo genetic testing? | Protects siblings, parents, and children |
How does this impact family planning? | Supports informed decisions about children |
What treatments or management options do you recommend? | Sets a symptom-management plan |
How often should I have preventive cancer screenings? | Establishes the surveillance schedule |
Conclusion
Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a rare genetic disorder that increases your risk of tumors and belongs to the PTEN hamartoma tumor syndrome (PHTS) family alongside Cowden syndrome. [1] It usually results from a mutation in the PTEN gene, the gene that produces proteins which slow tumor growth, and, without that brake, cells can divide uncontrollably and form hamartomas and other tumors. [1] Symptoms vary widely from person to person, ranging from high birth weight, large head size, and low muscle tone to developmental delays, seizures, spine curvature, and skin findings, while about half of people with BRRS experience intellectual disabilities. [1]
Because there's no specific treatment, care focuses on managing each person's unique symptoms, often with physical and speech therapy, and on routine cancer surveillance for breast, uterine, thyroid, and kidney cancers, with children starting yearly thyroid ultrasounds at age 7. [1] BRRS is passed down in an autosomal dominant pattern, giving each child of an affected parent a 50% chance of inheriting it, which makes genetic counseling and family testing especially valuable. [1] Researchers have found no evidence that BRRS itself reduces life expectancy. [1]
Take the next step in understanding your health. If you create rare-disease or genetic-counseling education materials, Rinnit's library of infographic templates can help you turn topics like PTEN mutations, cancer screening schedules, and family inheritance into clear visual guides for your audience.
Frequently Asked Questions
What is Bannayan-Riley-Ruvalcaba syndrome?
BRRS is a rare genetic disorder that increases your risk of getting tumors. It's part of a group of conditions called PTEN hamartoma tumor syndrome (PHTS), which also includes Cowden syndrome. It's also known as Riley-Smith syndrome, Ruvalcaba-Myhre syndrome, Ruvalcaba-Myhre-Smith syndrome, or Bannayan-Zonana syndrome. [1]
What causes BRRS?
BRRS is usually caused by a mutation in the PTEN gene. Less commonly (about 10% of cases), it's caused by a large deletion of genetic material that includes all or part of the PTEN gene. The PTEN gene produces a protein that slows tumor growth; when it's missing or not working properly, cells can divide uncontrollably and form hamartomas and other tumors. [1]
Is BRRS inherited?
Yes. Parents can pass BRRS to their biological children through autosomal dominant inheritance. If one parent has one copy of the mutated PTEN gene, their child has a 50% chance of inheriting the condition. [1]
What are the symptoms?
Symptoms vary significantly and may include high birth weight and length, macrocephaly (large head), freckles on the penis, low muscle tone, speech and/or motor delays, intellectual disabilities (about 50% of people with BRRS), muscle weakness, intestinal hamartomas, hyperflexible joints, seizures, pectus excavatum, scoliosis, acanthosis nigricans, lipomas, angiolipomas, and hemangiomas. [1]
How is BRRS diagnosed?
Through genetic testing of the PTEN gene using gene sequencing, which examines each component of the gene for changes. If a PTEN gene mutation is found, the diagnosis is confirmed with 100% certainty. However, only about 60% of people with BRRS symptoms have an identifiable gene mutation, so up to 40% may receive a normal test result. [1]
Is there a treatment for BRRS?
There's no specific treatment. Care involves managing the signs and symptoms unique to each person, often with physical and speech therapy, plus routine cancer screening. [1]
What cancer screenings are recommended?
People with a documented PTEN gene mutation should follow Cowden syndrome screening guidelines, which include screening for breast cancer, uterine cancer, thyroid cancer, and kidney cancer. [1]
What screening is recommended for children?
For people under 18, providers may recommend a yearly thyroid ultrasound starting at age 7, a yearly skin check with physical examination, a neurodevelopmental evaluation, and a yearly hemoglobin test for early detection of intestinal hamartomas. [1]
What is the life expectancy for someone with BRRS?
Researchers haven't discovered an average life expectancy for BRRS, and there's no evidence that people with BRRS have a reduced life expectancy from the condition itself. [1] However, because of the higher risk of certain cancers at a younger age, some people could have cancer-related reduced life expectancy [1], which is why screening matters.
Can BRRS be prevented?
No. It's a genetic condition caused by a gene mutation, so it can't be prevented. People with BRRS can use genetic counseling to make informed decisions about healthcare and having biological children. [1]
Should my family members get tested?
If you have immediate family members with BRRS (biological siblings, parents, or children), ask your provider about PTEN genetic testing. It can show whether they carry the mutation and need routine cancer screenings, even if they have no symptoms. [1]
Who benefits from genetic counseling?
People with BRRS and their families. Genetic counseling helps people make informed decisions about testing, healthcare, and family planning. Talking with a counselor or social worker can also help with the emotions of a diagnosis, and support groups, local or online, can connect you with others who share the experience. [1]
What questions should I ask my provider?
Key questions include: Do I or my child have an identifiable PTEN mutation? Should I or my family members undergo genetic testing? How does this impact family planning? What management options do you recommend? How often should I have preventive cancer screenings?
Related Reading
Cowden Syndrome: Symptoms, Causes, Cancer Screening and What to Expect — What You Need to Know
Developmental Delay in Children: Signs, Types, Causes, and What Early Intervention Can Do
Genetic and Rare Diseases Information Center: Bannayan-Riley-Ruvalcaba Syndrome
National Organization for Rare Disorders: Bannayan-Riley-Ruvalcaba Syndrome
References
Cleveland Clinic. Bannayan-Riley-Ruvalcaba Syndrome (BRRS). Cleveland Clinic Health Library. Last updated December 6, 2022. Accessed October 15, 2026. https://my.clevelandclinic.org/health/diseases/24547-bannayan-riley-ruvalcaba-syndrome-brrs
Genetic and Rare Diseases Information Center (GARD). Bannayan-Riley-Ruvalcaba syndrome. National Institutes of Health. Last updated June 2026. Accessed October 15, 2026. https://rarediseases.info.nih.gov/diseases/5887/bannayan-riley-ruvalcaba-syndrome
National Library of Medicine. Bannayan-Riley-Ruvalcaba syndrome. MedlinePlus Genetics. Last updated March 3, 2021. Accessed October 15, 2026. https://medlineplus.gov/genetics/condition/bannayan-riley-ruvalcaba-syndrome/
National Organization for Rare Disorders (NORD). Bannayan-Riley-Ruvalcaba Syndrome. NORD Rare Disease Database. Last updated January 20, 2021. Accessed October 15, 2026. https://rarediseases.org/rare-diseases/ruvalcaba-syndrome/
Yehia L, Keel E, Eng C. The clinical spectrum of PTEN mutations. Annu Rev Med. 2020;71:103-116. PMID: 31433956. https://doi.org/10.1146/annurev-med-052218-125823
Hendricks LAJ, Hoogerbrugge N, Schuurs-Hoeijmakers JHM, et al. A review on age-related cancer risks in PTEN hamartoma tumor syndrome. Clin Genet. 2021;99(2):219-225. PMID: 33140411. https://doi.org/10.1111/cge.13875
Baran JA, Tsai SD, Isaza A, et al. The clinical spectrum of PTEN hamartoma tumor syndrome: exploring the value of thyroid surveillance. Horm Res Paediatr. 2020;93(11-12):634-642. PMID: 33887726. https://doi.org/10.1159/000515731
Varga EA, Pastore M, Prior T, et al. The prevalence of PTEN mutations in a clinical pediatric cohort with autism spectrum disorders, developmental delay, and macrocephaly. Genet Med. 2009;11(2):111-117. PMID: 19265751. https://doi.org/10.1097/GIM.0b013e31818fd762
Medical disclaimer
The information provided in this article is for educational purposes only and is not intended as medical advice. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. If you have a family member with BRRS or suspect a genetic condition in your child, talk with your healthcare provider about PTEN testing and cancer screening.
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