Retinal hemangioblastomas in Von Hippel‐Lindau germline mutation carriers: progression, complications and treatment outcome

Abstract

AbstractPurposeEvaluating the phenotype, complications and treatment outcome of retinal hemangioblastomas (RH) and correlating this features with the genotype of Von Hippel‐Lindau (VHL) germline mutation carriers.MethodsRetrospective analysis of the medical and genetic records of 21 individuals with a VHL germline mutation and a diagnosis of RH. Germline mutation status was correlated to phenotype, complications, treatment methods and outcomes. Mutations were categorized in two genotypic categories: the truncating mutation (TM) group and the missense mutation (MM) group.ResultsFrom the 36 VHL germline mutation carriers, 21 VHL patients developed RH. Prevalence of RH in VHL disease was higher in TM carriers (15 of 21, 68.2%) vs. 40% of the MM carriers (6 of 15). The mean age of diagnosis of RH was 25.7 years. There was no significant difference in age of diagnosis of RH between genotypic categories (P = 0.931). Mean follow‐up duration was 16.3 years and did not differ significantly between the mutation groups (P = 0.383). Bilateral involvement was observed in 66.7% of the patients. Missense mutation (MM) carriers (n = 6) developed more RH (more than 5 RH: 50.0% vs. 38.5%), had a larger extent of peripheral retinal involvement of ocular VHL disease (66.7% vs. 35.7% all quadrants involved) and developed more progression‐related complications compared to TM carriers (n = 15) (100% vs. 46.7%). Complete tumor regression at last recorded visit was achieved in fifteen patients (71.4%). Moderate (VA 20/80 to 20/200) to severe (less than VA 20/200) visual impairment was observed in 53.3% of the eyes of MM carriers and 28.1% of the eyes of TM carriers at last recorded visit.ConclusionsGermline mutation status might play a role in the course of progression of RH in VHL disease. In our observational study, VHL missense mutation carriers had a more complicated progression of RH than carriers of a truncating mutation.