Bannayan-Riley-Ruvalcaba Syndrome
Bannayan-Riley-Ruvalcaba Syndrome (BRRS)
BRRS is a rare genetic condition characterized by macrocephaly, intestinal polyposis, and pigmented macules of the penis. It belongs to the PTEN hamartoma tumor syndrome (PHTS) spectrum.
Key Points
- Autosomal dominant inheritance
- Caused by mutations in the PTEN tumor suppressor gene
- High risk for both benign and malignant tumors
- Significant overlap with Cowden syndrome
- Requires multidisciplinary management approach
Clinical Manifestations
Growth & Development
- Macrocephaly (head circumference >97th percentile)
- Developmental delay in 50% of cases
- Motor delays and hypotonia in infancy
- Speech delays common
Dermatological Features
- Pigmented macules on glans penis in males
- Multiple lipomas
- Café-au-lait spots
- Hemangiomas
- Acanthosis nigricans
Gastrointestinal Manifestations
- Intestinal polyposis (hamartomatous)
- Usually present by age 10
- Risk for colorectal cancer
- Potential for intussusception
Additional Features
- High-arched palate
- Joint hyperextensibility
- Scoliosis
- Pectus excavatum
- Seizures in some cases
Genetics & Pathophysiology
Genetic Basis
- PTEN gene mutation on chromosome 10q23.3
- Autosomal dominant inheritance
- 80% of cases have identifiable PTEN mutations
- High penetrance but variable expressivity
Molecular Mechanisms
- PTEN functions as tumor suppressor
- Regulates PI3K/AKT/mTOR pathway
- Loss of function leads to:
- Increased cell proliferation
- Decreased apoptosis
- Altered cell migration
Diagnosis & Management
Diagnostic Criteria
- Clinical diagnosis requires presence of:
- Macrocephaly
- Hamartomas (including lipomas, hemangiomas)
- Penile macules in males
- Genetic testing confirms diagnosis
Surveillance Recommendations
- Annual physical examination
- Regular developmental assessment
- Baseline thyroid ultrasound
- Regular colonoscopy starting age 35
- Annual dermatologic examination
- Consider breast cancer screening in adults
Management Approach
- Multidisciplinary team required:
- Pediatrician
- Clinical geneticist
- Gastroenterologist
- Neurologist
- Developmental specialist
- Dermatologist
- Regular monitoring of growth and development
- Early intervention for developmental delays
- Surgical management of symptomatic hamartomas
