Von Hippel-Lindau disease
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Web Resources for Von Hippel-Lindau disease
ICD 10 code: Q85.5
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Medpedia on Von Hippel-Lindau disease (Less technical, good quality control)
Wikipedia on Von Hippel-Lindau disease (Less technical, ? quality control)
Von Hippel-Lindau disease (Von Hippel-Lindau syndome,VHL) is an autosomal dominant phakomatosis due to mutations of the VHLgene at 3p25.3. It is the main cause of adult inherited renal cancer and is characterised by:
- Haemangioblastomas in the cerebellum, spinal cord or retina (retinal angioma).
- Associated with:
- Renal angioma
- Renal cysts - important differential diagnosis of polycystic kidney disease
- Clear-cell renal cell carcinoma
- Phaeochromocytoma - 20%[1]
- Neuroendocrine pancreatic tumours
- Pancreatic cysts
- Hepatic cysts
- Endolymphatic sac tumours
Contents |
Historical
Multiple descriptions in retrospect but linked into a coherent whole in 1926 by Arvid Lindau. The suggestion as to the name used today was made in 1964[2]:
Epidemiology
- Incidence 1 in 36000
- Manifest usually between 18 - 30 years[5]
- Cerebellar hemangioblastoma is the most common presenting manifestation[6]
Diagnosis
Clinical diagnosis
- One major manifestation of von Hippel-Lindau disease in patients with a familial history
- One major manifestation of von Hippel-Lindau disease and demonstrated mutation of gene
- At least two major manifestations including one haeman-gioblastoma in isolated cases
There is evidence that the phenotype is modified by variations in the cyclin D1 gene on chromosome 11q13.
Classification
The 1991 classification and its subsequent subclassification depends on knowledge of the genetics[7][8].
- Type 1
- Gene deletions or specific missense mutations
- No pheochromocytoma
- Type 2
- Usually specific missense mutations
- With pheochromocytoma
- About 7% of all presentations
- Type 2A
- Low risk renal cancer
- Type 2B
- High risk renal cancer
- Mutations within part of gene coding for alpha domain of the VHL protein which results in the disruption of the interaction between the VHL protein and elongin C
- Type 2C
- Only pheochromocytoma, no risk renal cancer due to loss of the nearby HSPC300 gene which confers protection against renal clear cell carcinoma[9]
References
- ↑ Iliopoulos O, Chan-Smutko G, Gonzalez RG, Louis DN, Stone JR. Case records of the Massachusetts General Hospital. Case 23-2006. A 36-year-old man with numbness in the left corrected. hand and hypertension. The New England journal of medicine. 2006 Jul 27; 355(4):394-402.(Link to article – subscription may be required.)
- ↑ MELMON KL, ROSEN SW. LINDAU'S DISEASE. REVIEW OF THE LITERATURE AND STUDY OF A LARGE KINDRED. The American journal of medicine. 1964 Apr; 36:595-617.
- ↑ von Hippel E. In: Vorstellung eines Patienten mit einer sehr ungewöhnlichen Netzhaut. XXIV Verstellung der ophthalmologischen Gesellschaft (Heidelberg, 1895). Wiesbaden: JF Bergmann Verlag, 1896: 269
- ↑ Lindau A. Studien über Kleinhirnzysten. Bau, Pathogenese und Beziehungen zur Angiomatosis retinae. Acta Pathol Microbiol Scand 1926; S1: 1-128
- ↑ Richard S, Graff J, Lindau J, Resche F. Von Hippel-Lindau disease. Lancet. 2004 Apr 10; 363(9416):1231-4.(Link to article – subscription may be required.)
- ↑ Maddock IR, Moran A, Maher ER, Teare MD, Norman A, Payne SJ, Whitehouse R, Dodd C, Lavin M, Hartley N, Super M, Evans DG. A genetic register for von Hippel-Lindau disease. Journal of medical genetics. 1996 Feb; 33(2):120-7.
- ↑ Neumann HP, Wiestler OD. Clustering of features of von Hippel-Lindau syndrome: evidence for a complex genetic locus. Lancet. 1991 May 4; 337(8749):1052-4.
- ↑ Zbar B, Kishida T, Chen F, Schmidt L, Maher ER, Richards FM, Crossey PA, Webster AR, Affara NA, Ferguson-Smith MA, Brauch H, Glavac D, Neumann HP, Tisherman S, Mulvihill JJ, Gross DJ, Shuin T, Whaley J, Seizinger B, Kley N, Olschwang S, Boisson C, Richard S, Lips CH, Lerman M. Germline mutations in the Von Hippel-Lindau disease (VHL) gene in families from North America, Europe, and Japan. Human mutation. 1996; 8(4):348-57.(<348::AID-HUMU8>3.0.CO;2-3 Link to article – subscription may be required.)
- ↑ Cascón A, Escobar B, Montero-Conde C, Rodríguez-Antona C, Ruiz-Llorente S, Osorio A, Mercadillo F, Letón R, Campos JM, García-Sagredo JM, Benítez J, Malumbres M, Robledo M. Loss of the actin regulator HSPC300 results in clear cell renal cell carcinoma protection in Von Hippel-Lindau patients. Human mutation. 2007 Jun; 28(6):613-21.(Link to article – subscription may be required.)
