Bannayan-Riley-Ruvalcaba syndrome, etiology, clinical manifestations, diagnostic approaches, and current therapeutic...

Bannayan-Riley-Ruvalcaba Syndrome (BRRS) is a rare genetic disorder caused by germline mutations in the phosphatase and tensin homolog (PTEN) gene, leading to overgrowth and classified under PTEN hamartoma tumor syndrome (PHTS). It manifests with systemic features, including cutaneous, neurodevelopmental, and skeletal abnormalities, and is strongly associated with cancer risk. A literature review was conducted using PubMed and Web of Science databases up to April 2025, focusing on BRRS etiology, clinical features, diagnosis, and management. Most BRRS cases involve germline PTEN mutations, though some patients lack them. Clinical manifestations vary, with macrocephaly, lentiginous genital macules, intestinal polyps, and vascular anomalies being most common. Diagnosis is difficult due to the absence of standardized criteria; therefore, phenotypic assessment, molecular testing, imaging, and age-based considerations are essential. Management requires a multidisciplinary approach aimed at symptom control, early detection of malignancy, and family screening. Early recognition of BRRS features, along with prompt referral and intervention, can significantly improve outcomes. The lack of diagnostic guidelines and limited treatment options highlights the need for further research to establish standardized diagnostic and therapeutic strategies.