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

Von Hippel-Lindau (VHL) disease is a rare hereditary cancer predisposition syndrome associated with the development of central nervous system hemangioblastomas from childhood. The natural history of these lesions in pediatric patients remains poorly characterized, particularly regarding the factors that predict progression from radiological surveillance to neurosurgical intervention. This multicenter retrospective observational study aims to identify clinical, radiological, and genetic predictors of surgical indication in children with VHL-associated CNS hemangioblastomas and to evaluate their long-term neurological and functional outcomes. The findings may contribute to optimizing surveillance strategies and improving clinical decision-making in this rare population.

Study Overview

• Status: Not yet recruiting
• Conditions: Von Hippel-Lindau Disease; Central Nervous System Hemangioblastoma

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 25

Contacts and Locations

• Study Contact: Name: Amr ABDELHAKAM; Phone Number: +330(1)86678473; Email: amr.abdelhakam@aphp.fr

Study Locations

• France
  • Lille, France
    • Hôpital Roger Salengro, CHU Lille
    • Contact: Mélodie-Anne KARNOUB
    • Contact: Email: melodie-anne.karnoub@chru-lille.fr
  • Lyon, France
    • Hôpital Femme Mère Enfant, HCL
    • Contact: Federico DI ROCCO; Email: federico.dirocco@chu-lyon.fr
    • Contact: x
  • Paris, France
    • Hopital Necker
    • Contact: Kevin BECCARIA; Email: kevin.beccaria@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Pediatric patients diagnosed with Von Hippel-Lindau disease before the age of 18 years and presenting with at least one central nervous system hemangioblastoma

Description

Inclusion Criteria:

• Age under 18 years at diagnosis of Von Hippel-Lindau disease
• Presence of at least one central nervous system hemangioblastoma
• Available clinical, radiological and genetic data

Exclusion Criteria:

• Insufficient follow-up data to assess clinical or radiological progression
• Opposition from the child or his/her parents

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transition from radiological surveillance to neurosurgical intervention for a CNS hemangioblastoma.	Occurrence of a neurosurgical procedure performed for a previously monitored central nervous system hemangioblastoma, regardless of the indication (radiological progression, symptom development, neurological deficit, cyst formation, syringomyelia, hydrocephalus, hemorrhage, or other documented clinical reasons).	From diagnosis of CNS hemangioblastoma to last available follow-up, assessed retrospectively over the 2010-2025 study period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association between timing of surgery and neurological outcome	Evaluation of whether neurosurgical intervention performed before the occurrence of severe neurological deficit, hemorrhage, or hydrocephalus is associated with a better neurological outcome at last follow-up.	From neurosurgical intervention to last available follow-up, assessed retrospectively over the 2010-2025 study period
Number of neurosurgical interventions	Total number of neurosurgical procedures performed for CNS hemangioblastomas during follow-up.	From diagnosis of CNS hemangioblastoma to last available follow-up, assessed retrospectively over the 2010-2025 study period
Chronic neurological deficit	Occurrence or persistence of chronic neurological deficits during follow-up, including motor, sensory, cerebellar, cranial nerve, or sphincter deficits. Time Frame: From diagnosis to last available follow-up.	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	Number of high-risk patient subgroups identified according to clinical, radiological, and genetic characteristics.	Through study completion, up to 15 years.

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): July 15, 2026
• Primary Completion (Estimated): July 15, 2027
• Study Completion (Estimated): July 15, 2027

Study Registration Dates

• First Submitted: July 6, 2026
• First Submitted That Met QC Criteria: July 13, 2026
• First Posted (Actual): July 15, 2026

Study Record Updates

• Last Update Posted (Actual): July 15, 2026
• Last Update Submitted That Met QC Criteria: July 13, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Natural history; Pediatric neurosurgery; Von Hippel-Lindau disease; Central nervous system hemangioblastoma; Surgical indication; Long-term neurological outcome
• Additional Relevant MeSH Terms: Ciliopathies; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Congenital Abnormalities; Abnormalities, Multiple; Neurocutaneous Syndromes; Angiomatosis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; von Hippel-Lindau Disease
• Other Study ID Numbers: APHP260832

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No