BannayanRileyRuvalcaba

Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a rare genetic disorder that belongs to the group of PTEN hamartoma tumor syndromes. It is caused by pathogenic variants in the PTEN gene and is inherited in an autosomal dominant manner, though many cases arise de novo. BRRS is characterized by a combination of distinctive physical and developmental features that vary in severity among individuals.

The most common clinical features include macrocephaly (an abnormally large head circumference) present from birth, developmental delay or intellectual disability, and, in some cases, autism spectrum behaviors. Mucocutaneous pigmented lesions—freckling on the lips, tongue, and genitalia—are another hallmarks of BRRS, often described as penile freckling in males. Additional findings can include intestinal hamartomatous polyps, lipomas, vascular or other benign malformations, and sometimes congenital anomalies. GI polyps may lead to gastrointestinal symptoms or bleeding in some patients.

Diagnosis is based on clinical assessment guided by the characteristic features and confirmed by genetic testing for a pathogenic PTEN variant. BRRS is part of the broader PTEN hamartoma tumor syndrome spectrum, so differential diagnosis includes related conditions such as Cowden syndrome. Management is multidisciplinary and individualized, focusing on symptom treatment and appropriate surveillance for PTEN-associated cancers. This may include regular monitoring for thyroid, breast, endometrial, and renal cancers, among others, in accordance with PTEN-related cancer risk guidelines and family history. Genetic counseling is recommended for affected individuals and their families.