title: Survival and causes of death in patients with von Hippel-Lindau disease.
abstract: Historically, the survival of patients with von Hippel-Lindau disease (vHL) has been poorer than that of the general population. We aimed to determine whether the survival of VHL mutation carriers and their risk of vHL-related death has changed over time and how it has been affected by sex, genotype and surveillance attendance.
  
  
  
  In a retrospective cohort study, we included all known Danish vHL families with a VHL mutation. We assessed the survival and causes of death for 143 VHL mutation carriers using Cox regression models and compared vHL survival with that of 137 siblings without vHL. vHL life expectancy was compared with the general population using a relative survival model.
  
  
  
  The estimated mean life expectancies for male and female patients born in 2000 were 67 and 60 years, respectively. Survival is influenced by the sex and genotype of the patient. Female patients have a significantly higher risk of vHL-related death than male patients (HR=2.25, 95% CI 1.20 to 4.20, p=0.011). Overall, 79% (53 of 67) of deaths were vHL-related, but the risk of vHL-related death has decreased over time, as has the frequency of renal cell carcinoma (RCC)-related death. Surveillance is especially beneficial for truncating mutation carriers, who have the greatest RCC and central nervous system (CNS) hemangioblastoma risk.
  
  
  
  vHL survival has improved over time and has become closer to that of siblings without vHL and the general population. Even though the risk of vHL-related death has decreased significantly, the main cause of death is still CNS hemangioblastomas and hence improved treatment options are essential.
authors.affiliation: Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Marie Louise Mølgaard
authors.initials: ML
authors.lastname: Binderup
authors.affiliation: Department of Clinic of Cognitive Therapy, Mental Health Center Sct. Hans, Capital Region of Denmark, Roskilde, Denmark.
authors.forename: Annette Møller
authors.initials: AM
authors.lastname: Jensen
authors.affiliation: Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.|Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Esben
authors.initials: E
authors.lastname: Budtz-Jørgensen
authors.affiliation: Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Marie Luise
authors.initials: ML
authors.lastname: Bisgaard
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000235:genetics; D002423:Cause of Death; D002648:Child; D005260:Female; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D018325:Hemangioblastoma / Q000235:genetics; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D012189:Retrospective Studies; D055815:Young Adult; D006623:von Hippel-Lindau Disease / Q000235:genetics* / Q000401:mortality*
keywords: Clinical genetics; Life expectancy; Surveillance; Survival; von Hippel-Lindau disease