Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Aug;98(5):464-471.
doi: 10.1111/aos.14360. Epub 2020 Jan 30.

Retinal haemangioblastomas in von Hippel-Lindau germline mutation carriers: progression, complications and treatment outcome

Anass Hajjaj  1 , Koen A van Overdam  2 , Rogier A Oldenburg  3 , Anna E Koopmans  1 , Ans M W van den Ouweland  3 , Annelies de Klein  3 , Emine Kiliç  1
Affiliations

Retinal haemangioblastomas in von Hippel-Lindau germline mutation carriers: progression, complications and treatment outcome

Anass Hajjaj et al. Acta Ophthalmol. 2020 Aug.

Abstract

Purpose: Evaluation of phenotype and treatment outcome of retinal haemangioblastomas (RH) in von Hippel-Lindau (VHL) disease and correlation of these features with the genotype of VHL germline mutation carriers.

Methods: Retrospective analysis of a longitudinal cohort of 21 VHL germline mutation carriers and RH. Clinical and genetic data were obtained to analyse the correlation of genotype with phenotype and treatment outcomes.

Results: All patients were categorized in two genotypic categories: missense mutations (MM) and truncating mutations (TM). Mean follow-up duration was 16.3 years and did not differ significantly between mutation groups (p = 0.383). Missense mutations (MM) carriers (n = 6) developed more progression-related complications compared to TM carriers (n = 15) (p = 0.046). Vitreoretinal surgery was more often applied in MM carriers (p = 0.036). Moderate (visual acuity (VA)20/80 to 20/200) to severe (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.

Conclusion: Missense mutations in VHL patients seem to have a higher prevalence of progression-related complications. Missense mutations (MM) carriers required therefore more often vitreoretinal surgical treatment with a worse treatment outcome. Genetic analysis may play a role in determining a pro-active treatment strategy and prognosis for RH.

Keywords: Lindau; benign tumours; clinical genetics; haemangioblastoma; retina; von Hippel - Lindau.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Peripheral retinal haemangioblastoma with dilated and tortuous feeding vessels, surrounded by detachment and exudation that extends into the macula.
Figure 2
Figure 2
Line graph showing the regression rate of treated haemangioblastomas relative to the number of tumours arised during follow‐up. In both genotypic categories, the regression rate was 100% if merely one or two tumours arised. Missense mutation carriers showed a faster decrease of the regression rate when tumour number increased.
Figure 3
Figure 3
Bar graph showing the distribution of the initial and last recorded best‐corrected visual acuities between genotypic categories. Whereas missense mutation carriers started with a better visual acuity in best‐ and worse‐seeing eye, at last recorded visit a larger percentage of severe visual impairment is observed in this genotypic category.
See this image and copyright information in PMC

References

    1. Avci R, Yilmaz S, Inan UU, Kaderli B & Cevik SG (2017): Vitreoretinal surgery for patients with severe exudative and proliferative manifestations of retinal capillary hemangioblastoma because of Von Hippel‐Lindau disease. Retina 37: 782–788. - PubMed
    1. Binderup ML, Budtz‐Jorgensen E & Bisgaard ML (2016): Risk of new tumors in von Hippel‐Lindau patients depends on age and genotype. Genet Med 18: 89–97. - PubMed
    1. Bohling T, Hatva E, Kujala M, Claesson‐Welsh L, Alitalo K & Haltia M (1996): Expression of growth factors and growth factor receptors in capillary hemangioblastoma. J Neuropathol Exp Neurol 55: 522–527. - PubMed
    1. Carmeliet P, Dor Y, Herbert JM et al. (1998): Role of HIF‐1alpha in hypoxia‐mediated apoptosis, cell proliferation and tumour angiogenesis. Nature 394: 485–490. - PubMed
    1. Chan CC, Collins AB & Chew EY (2007): Molecular pathology of eyes with von Hippel‐Lindau (VHL) Disease: a review. Retina 27: 1–7. - PMC - PubMed

LinkOut - more resources