Pediatric Von Hippel-Lindau Disease: Natural History, Predictive Factors, and Long-Term Functional Outcomes of Central Nervous System Hemangioblastomas

Von Hippel-Lindau (VHL) disease is an autosomal dominant hereditary disorder caused by pathogenic variants in the VHL gene and characterized by the development of multiple benign and malignant tumors, including central nervous system (CNS) hemangioblastomas. In pediatric patients, CNS hemangioblastomas may remain asymptomatic for years before demonstrating periods of growth, cyst formation, neurological deterioration, or other complications requiring neurosurgical intervention. Despite regular radiological surveillance, there is currently no robust pediatric predictive model to identify lesions at highest risk of progression toward surgery.

This multicenter retrospective observational study aims to establish a pediatric cohort of patients diagnosed with VHL before the age of 18 years and presenting at least one CNS hemangioblastoma. Clinical, radiological, genetic, therapeutic, and follow-up data collected between 2010 and 2025 will be retrospectively extracted from medical records. Variables of interest will include demographic characteristics, VHL genotype, tumor burden and localization, radiological evolution, symptom onset, neurological deficits, surgical indications, operative procedures, postoperative complications, and long-term neurological and functional outcomes.

The primary objective is to identify clinical, radiological, and genetic factors associated with the transition from conservative surveillance to a neurosurgical indication. Secondary objectives include evaluating the relationship between surgical timing and functional outcome, describing long-term care pathways, identifying determinants of chronic neurological impairment, and defining high-risk subgroups that may benefit from personalized surveillance strategies. Statistical analyses will be performed using R software. By improving the understanding of the natural history and prognostic factors of pediatric VHL-associated CNS hemangioblastomas, this study seeks to support evidence-based management and improve long-term outcomes in affected children.

• Association between timing of surgery and neurological outcome [Срок оценки: From neurosurgical intervention to last available follow-up, assessed retrospectively over the 2010-2025 study period]
• Number of neurosurgical interventions [Срок оценки: From diagnosis of CNS hemangioblastoma to last available follow-up, assessed retrospectively over the 2010-2025 study period]
• Chronic neurological deficit [Срок оценки: From diagnosis of CNS hemangioblastoma to last available follow-up, assessed retrospectively over the 2010-2025 study period]
• Number of high-risk patient subgroups identified [Срок оценки: Through study completion, up to 15 years.]