title: Von hippel-lindau disease: a genetic and clinical review.
abstract: BACKGROUND
  Von Hippel-Lindau Disease (VHL) is an autosomal dominant inherited systemic cancer syndrome that gives rise to cystic and highly vascularized tumors in many organs, including the eye. Recent studies have contributed to the understanding of VHL pathophysiology, genetics, and the role of the VHL protein. This article reviews recent studies on VHL clinical findings, genetics and tumorigenesis.
  
  
  METHODS
  Literature review of articles on VHL genetics with correlation to clinical findings.
  
  
  RESULTS
  Genotype-phenotype correlation studies show that patients with a complete deletion mutation of the VHL gene, relative to participants with a missense or protein-truncating mutation, had better visual acuity and decreased tumorigenesis incidence of retinal hemangioblastomas. It has also been documented that higher levels of vascular endothelial growth factor (VEGF), hypoxia induced factor (HIF), and ubiquitin are found in ocular hemangioblastomas. The stromal foamy vacuolated cells seem to be the true tumor cells of the disease acting on the surrounding endothelial cells in ocular hemangioblastomas. Tumor cells and ocular lesions have shown increased levels of Erythropoietin (Epo), Epo receptor (EpoR), and CD133. Also, CXCR4, a CXC chemokine receptor, is expressed in retinal VHL hemangioblastomas. Recent studies suggest that the VHL mutation alone may not be sufficient to develop VHL-associated neoplasms. Studies suggest that targeting various proteins along with anti-angiogenesis molecules may be a better therapeutic approach than targeting VEGF alone.
  
  
  CONCLUSIONS
  Understanding of the mechanisms and genetics underlying VHL and its associated retinal hemangioblastomas has increased substantially in recent years. This knowledge suggests that future advances may include better identification of individuals at higher risk of vision loss and the development of novel individualized therapies.
authors.affiliation: Beetham Eye Institute, Joslin Diabetes Center , Boston, Massachusetts , USA and.
authors.forename: Nour Maya N
authors.initials: NM
authors.lastname: Haddad
authors.forename: Jerry D
authors.initials: JD
authors.lastname: Cavallerano
authors.forename: Paolo S
authors.initials: PS
authors.lastname: Silva
mesh_terms: D056726:Genetic Association Studies; D018325:Hemangioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D009154:Mutation; D019572:Retinal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D025801:Ubiquitin / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics; D006623:von Hippel-Lindau Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D051793:Hypoxia-Inducible Factor 1; D025801:Ubiquitin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human