Belzutifan for von Hippel–Lindau disease: Bibliometric analysis and a case report of multiple cerebral hemangioblastomas treatment

Introduction: Von Hippel–Lindau (VHL) syndrome is a rare hereditary condition marked by highly vascularized tumors. HIF-2α inhibitors, such as Belzutifan, are emerging as promising therapies. Methods: A PubMed search identified studies on VHL. Bibliometric analysis was conducted using VOSviewer and the Bibliometrix package in RStudio 4.4.3. Results: The United States leads in publications. Since 2022, Brazil, Spain, and Israel have maintained stable output. Tobias Else, Eric Jonasch, and Rodolfo F. Perini had four citations each. Aarhus University Hospital was the top-affiliated institution; Retinal Cases and Brief Reports was the most cited journal. We present a case of a 36-year-old woman with progressive right visual field loss. She had prior surgery for a pancreatic lesion of undetermined malignancy and a family history of VHL (six relatives). Magnetic resonance imaging (MRI) revealed a hyperintense optic pathway lesion extending to the thalamus and cerebellar nodules. Genetic testing confirmed a heterozygous c.500G>A variant in the VHL gene (chromosome 3p25.3), detected via capillary electrophoresis sequencing. Belzutifan (40 mg/day) led to improved vision and lesion regression over 9 months. Mild side effects included dizziness and fatigue. After a three-week discontinuation, visual decline occurred. Follow-up MRI showed optic nerve expansion (9 × 5 mm) and a 2 mm enhancing lesion in the left cerebellar hemisphere, suggestive of hemangioblastoma or glial neoplasm. Conclusion: Belzutifan demonstrated clinical and radiological efficacy with acceptable safety in this VHL case, aligning with findings from previous reports.