Von Hippel-Lindau Syndrome: An Updated Narrative Review for the First-Contact Clinician

Von Hippel-Lindau (VHL) syndrome is an autosomal dominant (AD) condition that increases the risk of developing CNS and retinal hemangioblastomas (R-Hb), as well as clear cell renal cell carcinoma (ccRCC), pheochromocytomas, pancreatic neuroendocrine tumors (pNETs), and endolymphatic sac tumors. CNS hemangioblastomas and renal cell carcinomas are among the leading causes of mortality in affected individuals. Recent therapeutic advances, particularly hypoxia-inducible factor 2 alpha (HIF-2α) inhibitors and vascular endothelial growth factor (VEGF)-targeted therapies, have yielded promising results. However, active surveillance remains the cornerstone of clinical management for reducing associated morbidity and mortality. Because VHL syndrome is multisystemic, a multidisciplinary clinical team is necessary to provide comprehensive care, including targeted pharmacotherapy and surgical resection, to prevent severe complications. This narrative review outlines the current diagnostic approach and follow-up protocols for VHL syndrome, highlighting recent therapeutic advances.