Background and aims We aimed to determine the frequency of von Hippel-Lindau disease (vHL) as the underlying cause of retinal hemangioblastoma and to estimate retinal hemangioblastoma incidence and prevalence in a national cohort study.
Methods Through the national patient register and vHL research database, we identified 81 patients diagnosed with a retinal hemangioblastoma in Denmark between 1977 and 2014. Consent was obtained for 54 living and 10 deceased patients with retinal hemangioblastoma. For each participant, we collected medical records and family information. Almost all (63 of 64) participants were or had previously been tested for mutations in the VHL gene.
Results Overall, 84% of the participants (54 of the 64) had vHL. Compared with the non-vHL patients, the vHL patients had their first retinal hemangioblastoma at a younger age (22.5 vs 40 years), and were more likely to have an asymptomatic first hemangioblastoma (80% vs 20%). Overall, 76% (41 of 54) of the vHL patients had a family history of vHL, while none of the patients without vHL did. Despite the rarity of the disease, on average more than eight new tumours are diagnosed each year due to multiple tumour development in vHL patients. The estimated prevalence of patients with retinal hemangioblastoma was up to 1 in 73 080 individuals.
Conclusion In the first national study in which almost all participants were genetically tested, vHL was the underlying cause of retinal hemangioblastoma in 84% of cases; more often than previously reported. We recommend that genetic and clinical vHL screening should be performed in all patients with retinal hemangioblastoma.
- Retinal hemangioblastoma
- von Hippel-Lindau
- genetic screening
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MLMB and A-SS contributed equally.
Contributors MLBI had the idea for and initiated the study. MLBI, MLMB, JFK and HUM designed the overall study structure. JFK and HUM primarily chose the ICD codes used in the register search. A-SS, MLMB and MLBI drafted the study protocol, which was approved by all authors. MLBI and JFK monitored data collection. MLMB and A-SS applied for the study approvals from the Regional Committees on Biomedical Ethics and the Data Protection Agency. MLMB obtained the register data. MG did the initial analysis of the register data. A-SS obtained the medical records for the patients with possible retinal hemangioblastoma and evaluated these data together with JFK, HUM, MLMB and MLBI. MLMB and A-SS and contacted possible participants, obtained study consent and interviewed the participants. MLMB did the majority of the laboratory analyses and interpreted the laboratory results together with MLBI. A-SS did the first part of the initial data analysis, and MG did the statistical analysis. All authors interpreted the data as a whole. A-SS and MLMB drafted the first version of the manuscript. All authors revised the paper and approved the final version of the manuscript.
Funding The study was financially supported by Synoptikfonden, Copenhagen, the Danish Cancer Society (R20-A968-10-S2), the Lundbeck Foundation (R48-A4839) and the Danish Association for patients with von Hippel-Lindau disease and their relatives. The funding organisations had no role in the design or conduct of this research.
Competing interests None declared.
Patient consent Obtained.
Ethics approval The study was approved by the Regional Committees on Biomedical Ethics (journal no. H-2-2010-012) and the Data Protection Agency (journal no. 2013-54-0582).
Provenance and peer review Not commissioned; externally peer reviewed.