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Angiomatosis of the Retina and the Cerebellum (von Hippel-Lindau Syndrome)

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Neurocutaneous Disorders

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Abstract

Haemangioblastomas in the brain, spinal cord, and retina, endolymphatic sac tumours, and clear-cell renal carcinomas constitute the two types of autosomal dominant von Hippel-Lindau syndrome. The gene is mapped to chromosome 3 and regulates the production of vascular endothelial growth factor (VEGF). The by-product protein from this tumour suppressor gene inhibits transcription by binding to elongin B and elongin C. Mutations in type 1 VHL are usually large deletion or truncation, whereas missense mutations occur in type 2 VHL. Patients may present with holocranial or positional headaches, vomiting, truncal and axial ataxia, most commonly during late teens and young adulthood, mandating imaging surveillance starting in childhood. Symptomatic treatment is available, but a cure remains elusive. A multidisciplinary team will best suit the needs of patients with von Hippel-Lindau syndrome.

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References

  1. von Hippel E. Vorstellung eines Patienten mit einer sehr ungewohnlichen Netzhaut. In: XXIV Vorstellung der ophthalmologischen Gesellschaft (Heidelberg 1895). Wiesbaden: Bergman JF Verlag; 1896.

    Google Scholar 

  2. von Hippel E. Über eine sehr seltene Erkrankung der Netzhaut. Albrecht Von Graefes Arch Ophthalmol. 1904;59:83–106.

    Article  Google Scholar 

  3. Collins ET. Intraocular growths. Two cases brother and sisters, with peculiar vascular new growth, probably primarily retinal, affecting both eyes. Trans Ophthal Soc (UK). 1894;14:141–9.

    Google Scholar 

  4. Czermak W. Pathologisch-anatomischer Befund bei der von Hippel beschriebenen sehr seltenen Netz-Hauterkrankung. Ber Ophthal Ges. 1906;32:184.

    Google Scholar 

  5. von Hippel E. Die anatomische Grundlage der von mir beschriebenen “sehr seltenen Erkrankung der Netzhau”. Albrecht Von Graefes Arch Ophthalmol. 1911;79:350–77.

    Article  Google Scholar 

  6. Lindau A. Studien uber Kleinhirnzysten. Bau, Pathogenese und Beziehungen zur Angiomatosis retinae. Acta Pathol Microbiol Scand. 1926;1:1–128.

    Google Scholar 

  7. Lindau A. Zur Frage der Angiomatosis retinae und ihrer Hirnkomplika- tionen. Acta Ophthalmol. 1927;4:193–226.

    Article  Google Scholar 

  8. Crossey PA, Foster K, Richards FM, et al. Molecular genetic investigations of the mechanism of tumourigenesis in von Hippel-Lindau disease: analysis of allele loss in VHL tumours. Hum Genet. 1994;93:53–8.

    Article  CAS  PubMed  Google Scholar 

  9. Maher ER, Neumann HP, Richard S. von Hippel-Lindau disease: a clinical and scientific review. Eur J Hum Genet. 2011;19:617–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Wind JJ, Lonser RR. Management of von Hippel-Lindau disease-associated CNS lesions. Expert Rev Neurother. 2011;11:1433–40.

    Article  PubMed  Google Scholar 

  11. Nielsen SM, Rubinstein WS, Thull DL, et al. Long-term outcomes, branch-specific expressivity, and disease-related mortality in von Hippel-Lindau type 2A. Fam Cancer. 2011;10:701–7.

    Article  PubMed  Google Scholar 

  12. Robinson CM, Ohh M. The multifaceted von Hippel-Lindau tumour suppressor protein. FEBS Lett. 2014;588:2704–11.

    Article  CAS  PubMed  Google Scholar 

  13. Li M, Song J, Pytel P. Expression of HIF-1 regulated proteins vascular endothelial growth factor, carbonic anhydrase IX and hypoxia inducible gene 2 in hemangioblastomas. Folia Neuropathol. 2014;52:234–42.

    Article  PubMed  Google Scholar 

  14. Essers PB, Klasson TD, Pereboom TC, et al. The von Hippel-Lindau tumor suppressor regulates programmed cell death 5-mediated degradation of Mdm2. Oncogene. 2014;34:771–9.

    Article  PubMed  Google Scholar 

  15. Park MH, Choi KY, Jung Y, Min DS. Phospholipase D1 protein coordinates dynamic assembly of HIF-1a-PHD-VHL to regulate HIF-1a stability. Oncotarget. 2014;5:11857–72.

    Article  PubMed  PubMed Central  Google Scholar 

  16. De Krijger RR. Endocrine tumor syndromes in infancy and childhood. Endocr Pathol. 2004;15:223–6.

    Article  PubMed  Google Scholar 

  17. Chou A, Toon C, Pickett J, Gill AJ. von Hippel-Lindau syndrome. Front Horm Res. 2013;41:30–49.

    Article  CAS  PubMed  Google Scholar 

  18. Couch V, Lindor NM, Karnes PS, Michels VV. von Hippel-Lindau disease. Mayo Clin Proc. 2000;75:265–72.

    Article  CAS  PubMed  Google Scholar 

  19. Lonser RR, Glenn GM, Walther MC, et al. von Hippel-Lindau disease. Lancet. 2003;361(9374):2059–67.

    Article  CAS  PubMed  Google Scholar 

  20. Tsang SH, Tarun ST. Von Hippel-Lindau Disease. Adv Exp Med Biol. 2018;201:3.

    Article  Google Scholar 

  21. von Metso S. Hippel-Lindau disease. Duodecim. 2014;130:1867–73.

    PubMed  Google Scholar 

  22. Kanno H, Kuratsu J, Nishikawa R, et al. Clinical features of patients bearing central nervous system hemangioblastoma in von Hippel-Lindau disease. Acta Neurochir. 2013;155:1–7.

    Article  PubMed  Google Scholar 

  23. Cursiefen D, Dahlke C. von hippel lindau disease. J Pediatr. 2019;209:252.

    Article  PubMed  Google Scholar 

  24. Findeis-Hosey JJ, McMahon KQ, Findeis SK. Von Hippel-Lindau disease. J Pediatr Genet. 2016;5:116–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Crespigio J, Berbel LCL, Dias MA, et al. Von Hippel-Lindau disease: a single gene, several hereditary tumors. J Endocrinol Invest. 2018;41:21–31.

    Article  CAS  PubMed  Google Scholar 

  26. Bisceglia M, Galliani CA, Senger C, et al. Renal cystic diseases: a review. Adv Anat Pathol. 2006;13:26–56.

    Article  PubMed  Google Scholar 

  27. Park TY, Lee SK, Park J-S, et al. Clinical features of pancreatic involvement in von Hippel-Lindau disease: a retrospective study of 55 cases in a single center. Scand J Gastroenterol. 2015;50:360–7.

    Article  PubMed  Google Scholar 

  28. Schmidt D. Retinal angiomatosis. Klin Monbl Augenheilkd. 2005;222:90–109.

    Article  CAS  PubMed  Google Scholar 

  29. Wittström E, Nordling M, Andreasson S. Genotype-phenotype correlations, and retinal function and structure in von Hippel-Lindau disease. Ophthalmic Genet. 2014;35:91–106.

    Article  PubMed  Google Scholar 

  30. Maher ER, Yates JR, Harries R, et al. Clinical features and natural history of von Hippel-Lindau disease. Q J Med. 1990;77:151–61.

    Article  Google Scholar 

  31. Gong JS, Xu JM. Imaging manifestations of von Hippel-Lindau disease: a report of 3 cases. Chin Med J (Engl). 2005;118:519–22.

    Google Scholar 

  32. Binderup ML, Gimsing S, Kosteljanetz M, et al. von Hippel-Lindau disease: deafness due to a non-MRI-visible endolymphatic sac tumor despite targeted screening. Int J Audiol. 2013;52:771–5.

    Article  PubMed  Google Scholar 

  33. Mukherjee A, Karunanithi S, Bal C, Kumar R. 68Ga DOTANOC PET/CT aiding in the diagnosis of von Hippel-Lindau syndrome by detecting cerebellar hemangioblastoma and adrenal pheochromocytoma. Clin Nucl Med. 2014;39:920–1.

    Article  PubMed  Google Scholar 

  34. Aronow ME, Wiley HE, Gaudric A, et al. Von Hippel-Lindau. Update on pathogenesis and systemic aspects. Retina. 2019;39:2243–53.

    Article  CAS  PubMed  Google Scholar 

  35. Carlson ML, Thorn JJ, Driscoll CL, et al. Management of primary and recurrent endolymphatic sac tumors. Otol Neurotol. 2013;34:939–43.

    Article  PubMed  Google Scholar 

  36. Puataweepong P, Dhanachai M, Hansasuta A, et al. The clinical outcome of intracranial hemangioblastomas treated with LINAC-based stereotactic radiosurgery and radiotherapy. J Radiat Res. 2014;55:761–8.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Escudier B, Pluzanska A, Koralewski P, et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet. 2007;370:2103–11.

    Article  PubMed  Google Scholar 

  38. Rini BI, Halabi S, Rosenberg JE, et al. Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol. 2008;26:5422–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007;356:115–24.

    Article  CAS  PubMed  Google Scholar 

  40. Kim HC, Lee JS, Kim SH, et al. Sunitinib treatment for metastatic renal cell carcinoma in patients with von Hippel-Lindau disease. Cancer Res Treat. 2013;45:349–53.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Roma A, Maruzzo M, Basso U, et al. First-line sunitinib in patients with renal cell carcinoma (RCC) in von Hippel-Lindau (VHL) disease: clinical outcome and patterns of radiological response. Fam Cancer. 2015;14:309–16.

    Article  CAS  PubMed  Google Scholar 

  42. Hudes G, Carducci M, Tomczak P, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. Global ARCC Trial. N Engl J Med. 2007;356:2271–81.

    Article  CAS  PubMed  Google Scholar 

  43. Conti A, Santoni M, Amantini C, et al. Progress of molecular targeted therapies for advanced renal cell carcinoma. Biomed Res Int. 2013;9:419176.

    Google Scholar 

  44. Park BK, Kim CK, Park SY, Shen SH. Percutaneous radiofrequency ablation of renal cell carcinomas in patients with von Hippel-Lindau disease: indications, techniques, complications, and outcomes. Acta Radiol. 2013;54:418–27.

    Article  PubMed  Google Scholar 

  45. Vergaumen E, Christian A, Koch CA, et al. Von Hippel-Lindau disease: current challenges and future prospects. Onco Targets Ther. 2020;13:5669–90.

    Article  Google Scholar 

  46. Wiley H, Krivosic V, Gaudric A, et al. Management of retinal hemangioblastoma in von Hippel-Lindau disease. Retina. 2019;39:2254–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Hanakita S, Koga T, Shin M, et al. The long-term outcomes of radiosurgery for intracranial hemangioblastomas. Neuro Oncol. 2014;16:429–33.

    Article  PubMed  Google Scholar 

  48. Li CH, Liao PL, Yang YT, et al. Minocycline accelerates hypoxia-inducible factor-1 alpha degradation and inhibits hypoxia-induced neovasculogenesis through prolyl hydroxylase, von Hippel-Lindau-dependent pathway. Arch Toxicol. 2014;88:659–71.

    CAS  PubMed  Google Scholar 

  49. Grepin R, Guyot M, Giuliano S, et al. The CXCL7/CXCR1/2 axis is a key driver in the growth of clear cell renal cell carcinoma. Cancer Res. 2014;74:873–83.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Paediatric Neurology and Developmental Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Christos P. Panteliadis

  2. Department of Neurology, University of Washington, Seattle, WA, USA

    Ramsis Benjamin

Authors
  1. Christos P. Panteliadis
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  2. Ramsis Benjamin
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Correspondence to Christos P. Panteliadis .

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Editors and Affiliations

  1. Department of Paediatric Neurology and Developmental Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Christos P. Panteliadis

  2. Department of Neurology, University of Washington, Seattle, WA, USA

    Ramsis Benjamin

  3. Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Christian Hagel

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Panteliadis, C.P., Benjamin, R. (2022). Angiomatosis of the Retina and the Cerebellum (von Hippel-Lindau Syndrome). In: Panteliadis, C.P., Benjamin, R., Hagel, C. (eds) Neurocutaneous Disorders. Springer, Cham. https://doi.org/10.1007/978-3-030-87893-1_28

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  • DOI: https://doi.org/10.1007/978-3-030-87893-1_28

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-87892-4

  • Online ISBN: 978-3-030-87893-1

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