Bannayan-Riley-Ruvalcaba Syndrome is considered rare, with the prevalence estimated to be less than 1 in 200,000 individuals. As with many rare genetic disorders, the syndrome may be underdiagnosed or misdiagnosed, so the true prevalence may be higher. It affects both males and females equally and has been reported in various ethnicities.

BRRS is caused by mutations in the PTEN gene, which plays a crucial role in controlling cell division and preventing uncontrolled cell growth. PTEN acts as a tumor suppressor, and mutations in this gene can lead to an increased risk of developing benign tumors (hamartomas) as well as certain cancers. About 60% of cases of Bannayan-Riley-Ruvalcaba Syndrome are caused by mutations in the PTEN gene, and another 10% of cases are caused by a large deletion in the PTEN region. The disorder follows an autosomal dominant inheritance pattern, meaning only one copy of the mutated gene, inherited from one parent, is needed to cause the syndrome (see RareShare Guide on Genetic Inheritance). In some cases, the mutation occurs spontaneously without a family history.

The symptoms of BRRS can vary widely but typically include:

• Macrocephaly: A noticeably large head is a hallmark feature, usually evident at birth or shortly thereafter. Infants may also have an abnormally large body size (macrosomia)

• Developmental Delays: Children with BRRS may have delays in motor skills and cognitive development, though intelligence levels vary widely. These developmental delays can include sitting, crawling, and walking, but may improve with age.

• Hamartomas: Multiple benign tumors, particularly in the gastrointestinal tract, may develop. These include intestinal polyps, lipomas (fatty tumors), and hemangiomas (blood vessel growths).

• Skin Lesions: The presence of characteristic skin findings, such as subcutaneous lipomas and penile freckling in males, is common.

• Musculoskeletal Abnormalities: Some individuals may have joint hypermobility, scoliosis (curvature of the spine), or other orthopedic issues.

Diagnosis of BRRS is based on clinical findings, family history, and genetic testing. The presence of key symptoms like macrocephaly, skin lesions, and intestinal polyps raises suspicion of BRRS. Genetic testing to identify PTEN mutations provides a definitive diagnosis.

• Genetic Testing: Sequencing of the PTEN gene confirms the diagnosis of BRRS by identifying pathogenic mutations.

• Imaging Studies: MRI or CT scans may be used to assess macrocephaly and identify brain or spinal abnormalities.

• Endoscopy/Colonoscopy: These procedures can help detect and monitor intestinal polyps, which are common in BRRS.

• Skin Biopsy: A biopsy of suspicious skin lesions (lipomas or hemangiomas) may help characterize the benign tumors typical of the syndrome.

There is no cure for BRRS, and treatment focuses on managing symptoms and monitoring for potential complications, particularly the risk of cancer:

• Surveillance for Tumors: Regular screenings for cancers associated with PTEN mutations, such as breast, thyroid, and kidney cancers, are essential.

• Surgical Removal of Tumors: Lipomas and intestinal polyps can be surgically removed if they cause discomfort or complications, although they may recur.

• Developmental Support: Early intervention with physical, occupational, and speech therapy may help children with developmental delays achieve their potential.

• Monitoring of Polyps: Gastrointestinal polyps should be regularly monitored to prevent complications like bowel obstruction or malignancy.

The prognosis for individuals with BRRS varies depending on the severity of symptoms and the risk of developing cancers. Most people with BRRS live a normal lifespan, though they require lifelong monitoring for tumors and cancer risks due to PTEN mutations. With appropriate medical management, including regular screenings and treatment of benign and malignant growths, many individuals with BRRS can lead relatively normal lives, although developmental and intellectual challenges may persist.

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6. https://my.clevelandclinic.org/health/diseases/24652-hamartoma 

7. https://medlineplus.gov/genetics/condition/bannayan-riley-ruvalcaba-syndrome/