Bannayan-Riley-Ruvalcaba Syndrome (BRRS) is a rare genetic condition that presents from birth or becomes apparent in early childhood. It is characterized by a group of distinct features impacting growth and development. Individuals with BRRS often experience multiple benign tumors and tumor-like growths, alongside other physical characteristics. This article explains BRRS, its causes, diagnosis, management, and outlook.
Understanding the Syndrome
Bannayan-Ruvalcaba-Riley Syndrome is categorized as an overgrowth syndrome and a hamartomatous disorder. It is part of the PTEN Hamartoma Tumor Syndromes (PHTS), which includes Cowden syndrome and Proteus-like syndrome. These syndromes share common features and are all linked to genetic changes.
The underlying cause of BRRS is a mutation in the PTEN gene. This gene provides instructions for making an enzyme found in nearly all body tissues. The PTEN enzyme functions as a tumor suppressor, regulating cell division and preventing uncontrolled cell growth.
When a mutation occurs in the PTEN gene, it can reduce or eliminate the enzyme’s tumor suppressor function. This dysfunction allows certain cells to divide without proper control, leading to the development of hamartomas, which are benign growths made of abnormal cells and tissues, and other tumors. The inheritance pattern for BRRS is autosomal dominant, meaning only one copy of the altered gene is needed for the condition. If a parent has BRRS, there is a 50% chance for each child to inherit the mutation.
Recognizing the Signs
Individuals with Bannayan-Riley-Ruvalcaba Syndrome present with a range of characteristic features, though the severity and combination of these signs can vary significantly among affected individuals. Macrocephaly, an abnormally large head circumference, is a common feature, often present at birth or in early childhood. Many affected infants also have high birth weight and large body size, though growth typically slows during childhood, resulting in normal adult height and size.
The syndrome is also associated with the presence of hamartomas, which are benign, tumor-like growths. These can occur throughout the body; intestinal polyps are common, affecting about half of individuals with BRRS. Subcutaneous lipomas, benign fatty tumors beneath the skin, are also frequently observed. Other skin manifestations include angiolipomas (noncancerous growths of fat and blood vessels) and hemangiomas (red or purplish growths of abnormal blood vessels).
Males with BRRS often have pigmented macules, or dark freckles, on the penis. Developmental delays, particularly in speech and motor skills, are present in approximately half of children with BRRS, and intellectual disability can also occur. Muscle weakness or hypotonia (low muscle tone) and connective tissue abnormalities like joint laxity or hyperextensibility are also possible features. Skeletal anomalies like scoliosis or pectus excavatum may also be present.
Diagnosis and Management
Diagnosing Bannayan-Riley-Ruvalcaba Syndrome involves a combination of clinical evaluation and genetic testing. Healthcare providers suspect BRRS based on characteristic physical features like macrocephaly, lipomas, hemangiomas, and pigmented macules on the penis. While no international consensus criteria exist, clinical suspicion often leads to further investigation.
Genetic testing, specifically for mutations in the PTEN gene, plays a confirmatory role in diagnosis. Identifying a PTEN gene mutation confirms the BRRS diagnosis with high certainty. However, an identifiable PTEN gene mutation is found in approximately 60% of individuals with clinical symptoms, meaning some may have the syndrome without a detected mutation. Additional diagnostic tools include imaging studies, such as MRI for macrocephaly or colonoscopy for intestinal polyps.
The management of BRRS is multidisciplinary, involving specialists to address diverse symptoms and complications. This team may include pediatricians, geneticists, neurologists, and gastroenterologists. Management involves regular surveillance for complications, particularly the increased risk of cancers associated with PTEN mutations, such as breast, thyroid, endometrial, kidney, and colorectal cancers. For instance, yearly thyroid ultrasounds are recommended starting at age seven, and annual skin checks are advised for individuals over 18. Colonoscopies and biennial renal imaging may begin between ages 35-40, or earlier if symptoms arise. Symptomatic treatment and supportive therapies are also provided, including physical therapy for developmental delays or surgical removal of problematic lipomas or polyps.
Living with the Syndrome and Outlook
Living with Bannayan-Riley-Ruvalcaba Syndrome requires ongoing monitoring and early intervention due to potential complications, including cancer predisposition. Individuals with a confirmed PTEN gene mutation share similar cancer risks as those with Cowden syndrome, emphasizing the need for regular screenings for breast, thyroid, endometrial, and kidney cancers.
The general prognosis and quality of life for individuals with BRRS can vary widely, depending on the specific symptoms present and their severity. While no evidence suggests reduced average life expectancy directly from BRRS, the increased risk of certain cancers at younger ages means some individuals may experience a cancer-related impact on their lifespan. Proactive, lifelong multidisciplinary follow-up is important to reduce morbidity and improve quality of life.
Genetic counseling is a valuable resource for affected individuals and their families. It helps them understand the autosomal dominant inheritance pattern of BRRS and implications for family planning. It also guides asymptomatic family members in deciding whether to undergo PTEN mutation testing to determine their need for monitoring. Support groups, local or online, also provide a community for individuals and families navigating BRRS challenges.