Clinical characteristics of ocular angiomatosis in von Hippel-Lindau disease and correlation with germline mutation

Arch Ophthalmol. 1999 Mar;117(3):371-8. doi: 10.1001/archopht.117.3.371.


Objectives: To examine the epidemiologic and clinical characteristics of the ocular manifestations of von Hippel-Lindau (VHL) disease and to detect phenotype-genotype relationships of disease severity.

Design: A cross-sectional clinical and molecular genetic study.

Patients and methods: One hundred eighty-three affected VHL gene carriers from 81 unrelated pedigrees were interviewed and examined; clinical data were also obtained from 12 living and 39 deceased affected relatives. DNA extracted from venous blood was used to identify mutations in the VHL gene.

Results: The prevalence of ocular angiomatosis (hemangioblastomas) in von Hippel-Lindau disease was 67.8% (124/183), and the mean number of angiomas in gene carriers was 1.85 (range, 0-15). Neither prevalence nor angioma count increased with age. Severe vision loss in 1 or both eyes was associated with presentation at a young age. The cumulative probability of incurring vision loss by age 50 years was 35% in all gene carriers, 55% in those with angiomatosis, and significantly worse in those coming to us with symptoms. Angiomas were nonrandomly distributed in the fundus, occurring rarely at the posterior pole (1% of retinal tumors) and commonly on the optic disc (8% of eyes) and supratemporal retina. Complications of ocular angiomatosis included disc and retinal neovascularization; secondary angioma formation; retinal detachment, exudation, and membrane; and retinal and vitreous hemorrhage. Germ-line VHL mutations were detected in 161 of 183 patients and 69 (85%) of 81 pedigrees and included deletions (n= 16), missense (mutations causing amino acid substitutions; n = 24), nonsense (premature stop codons; n = 15), frameshift (n = 13), and splice-site (n = 1) mutations. There was no association between the type or position of mutation and the severity of ocular angiomatosis.

Conclusions: A systematic clinical description of a large cohort of VHL gene carriers further defines the ocular phenotype. There is no general influence of germline mutation on severity of ocular disease in VHL.

Clinical relevance: The ophthalmic and molecular genetic description of patients with VHL disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Cohort Studies
  • Cross-Sectional Studies
  • England / epidemiology
  • Female
  • Fluorescein Angiography
  • Fundus Oculi
  • Genotype
  • Germ-Line Mutation*
  • Hemangioblastoma / epidemiology
  • Hemangioblastoma / etiology*
  • Hemangioblastoma / genetics
  • Heterozygote
  • Humans
  • Male
  • Middle Aged
  • Pedigree
  • Phenotype
  • Prevalence
  • Retinal Neoplasms / epidemiology
  • Retinal Neoplasms / etiology*
  • Retinal Neoplasms / genetics
  • Vision Disorders / etiology
  • von Hippel-Lindau Disease / complications*
  • von Hippel-Lindau Disease / epidemiology
  • von Hippel-Lindau Disease / genetics