Bannayan-Riley-Ruvalcaba Syndrome - A Rare Genetic Condition

Introduction:

Bannayan-Riley-Ruvalcaba Syndrome (BRRS) is a rare genetic condition that occurs when changes happen in the PTEN tumor suppressor gene. PTEN denotes Phosphatase and TENsin homolog deleted on chromosome 10. Other names of BRRS include Bannayan Zonana syndrome, Riley Smith syndrome, Ruvalcaba-Myhre-Syndrome, and Ruvalcaba-Myhre-Smith Syndrome. Symptoms of the condition vary greatly, and it includes macrocephaly (abnormally large head ), changes in the blood vessels (hemangiomas), high birth weight, intellectual disability, thyroid problems, and hamartomas (tumor-like growth). This article will explain the BRRS syndrome and how it is managed in detail.

What Is Bannayan-Riley-Ruvalcaba Syndrome?

Bannayan-Riley-Ruvalcaba Syndrome (BRRS) is a genetic condition that increases the risk of tumors in a person. It is part of a group of disorders called the PTEN hamartoma tumor syndrome (PHTS). This group also includes Cowden syndrome.

What Causes Bannayan-Riley-Ruvalcaba Syndrome?

BRRS usually occurs when a mutation happens in the PTEN gene. The PTEN gene is responsible for producing proteins that slow down the growth of tumors. Since people with BRRS have damaged genes, they develop tumor-like growth and noncancerous tumors. Besides tumors, the risk of developing cancers in them is also high. The other reason for the occurrence of BRRS is when an enormous deletion of genetic material happens, including part or all of the PTEN gene. Parents can also pass their BRRS gene to their children through the autosomal dominant inheritance pattern. This pattern means that if a parent has the gene, there is a 50 percent chance that their child will inherit the condition.

What Symptoms Are Seen in Bannayan-Riley-Ruvalcaba Syndrome?

Signs and symptoms of the syndrome are present right from birth or become more apparent during early childhood. People diagnosed with the syndrome does not necessarily have the same feature. For example, when half of the people have normal development, the other half can have learning problems and face development delays. The symptoms seen in Bannayan-Riley-Ruvalcaba Syndrome vary significantly and include the following:

Growth Issues:

• High birth weight.

• Macrocephaly (abnormally large head).

• Macrosomia (large body size).

Developmental Issues:

• Development delays in motor skills like crawling, walking, and sitting or speech delays. The developmental delays usually improve as age progresses.

• Intellectual disabilities.

• Autism disorder. A PTEN gene mutation is noted in children diagnosed with an autism spectrum disorder.

• Hypotonia (low muscle tone).

• Muscle weakness.

• Seizures.

Skeletal Malformations:

• Hyper-flexible joints.

• Pectus excavatum is when the breast bones sink deep into the chest area.

• Scoliosis is an abnormal curvature in the spine where a person has a sideway curvature.

Skin Problems:

• Acanthosis nigricans is a darkish discoloration that occurs in the folds and creases of the body.

• The occurrence of freckles or pigmented macules in the penis.

• Angiolipomas (noncancerous tissues composed of blood vessels and fat).

Intestinal Problems:

• Hamartomas, or noncancerous growth called hamartomatous polyps, arise from the intestinal tract's abnormal cells and tissues.

Tumors:

• Hemangiomas (birthmarks developed from the blood vessels underneath the skin area).

• Lipomas (fatty tumors that are present beneath the skin area).

• Thyroid problems like Hashimoto's thyroiditis or multinodular goiter.

Is Cowden's Syndrome the Same as Bannayan-Riley-Ruvalcaba Syndrome?

No, Cowden's syndrome differs from BRRS syndrome even though they share the same features, like hamartomas and noncancerous growth, and they are at an increased risk of developing cancer. Mutations of the PTEN gene cause both Cowden's syndrome and Bannyan-Riley-Ruvalcaba syndrome. Therefore, both syndromes represent a group of conditions called the PTEN hamartoma tumor syndrome (PHTS). Earlier, Cowden's syndrome and BRRS were viewed as different conditions; however, recently, they have been classified under the PHTS as they are both associated with mutations that happened in the PTEN gene.

How Is Bannayan-Riley-Ruvalcaba Syndrome Diagnosed?

• If the healthcare practitioner suspects BRRS, they will recommend PTEN genetic testing.

• The usual test done is called gene sequencing. Doctors use this gene sequencing to examine the components of genes to check for any mutations or changes.

• Genetic testing is usually accurate. If a gene mutation is noted in the test, the diagnosis of BRRS is confirmed with 100 percent certainty.

• However, only 60 percent of BRRS symptoms have a noticeable gene mutation. So, there are chances that people with BRRS receive an expected result because of the unidentifiable gene mutation.

• This is due to certain limitations in the tests. Laboratories usually offer additional testing to detect any mutations missed by sequencing tests.

• Pediatric diagnosis is mainly based on macrocephaly, autism spectrum disorder, gastrointestinal polyps, vascular malformations like hemangiomas, and dermatological features.

How Is Bannayan-Riley-Ruvalcaba Syndrome Treated?

• There is no specific treatment for Bannayan-Riley-Ruvalcaba Syndrome.

• The management of BRRS usually involves treating the specific signs and symptoms associated with the syndrome.

• Specific screening guidelines are recommended for people with a PTEN gene mutation. These include screenings for uterine cancer, thyroid cancer, breast cancer, and kidney cancer.

• Genetic counseling is essential for people with BRRS syndrome.

• Asymptomatic family members can undergo PTEN gene testing to decide whether they need to follow the cancer screening guidelines.

Are There Any Surveillance Guidelines In Bannayan-Riley-Ruvalcaba Syndrome?

There are specific surveillance guidelines for each type of cancer. Screening does not begin when the cancer is diagnosed; it depends on a person's age. Doctors recommend certain screenings for people with BRRS below the age of 18. They include the following:

• A yearly ultrasound of the thyroid beginning from seven years of age.

• Neurodevelopment assessment.

• Yearly hemoglobin check-ups to detect early intestinal hamartomas.

• Physical examination, including the skin check-up.

• Women must perform self-breast examinations and yearly trans vagina ultrasounds, endometrial biopsies, and breast screenings from age 35 and above.

• Biennial renal imaging (scan of kidneys and their function) and colonoscopies are recommended between the ages of 35 to 40.

Can Bannayan-Riley-Ruvalcaba Syndrome Be Prevented?

Bannayan-Riley-Ruvalcaba Syndrome cannot be prevented as it is a genetic condition that arises from gene mutations. However, people with the syndrome can obtain counseling to make better decisions regarding their healthcare and having children. In addition, by undergoing appropriate screening, cancer can be diagnosed early, and appropriate management can be done.

Conclusion:

Bannayan-Riley-Ruvalcaba Syndrome is a genetic condition arising from gene mutations in the PTEN gene. The symptoms of the syndrome can vary from mild to severe. Even though there is no specific treatment for BRRS, the treatment is by managing the underlying conditions and symptoms. People affected by the syndrome undergo routine screening for breast, thyroid, kidney, and uterine cancer early to detect the presence of cancer and undergo treatment.