Skip to main content Accessibility help
×
Home
  • Print publication year: 2004
  • Online publication date: July 2009

7 - von Hippel–Lindau disease

Summary

Introduction

Von Hippel–Lindau (VHL) disease is an autosomal dominant disorder with high penetrance characterized by various benign and malignant tumors in multiple organ systems. The prevalence of VHL is approximately 1 in 36 000 to 1 in 53 000 births (Maher et al., 1991; Chauveau et al., 1996). Retinal angiomas, one of the hallmark VHL lesions, were initially described in 1904 by ophthalmologist Eugen von Hippel (1904). Pathologist Arvid Lindau (1927) demonstrated in 1927 the association of these retinal lesions with the cystic cerebellar tumors, spinal hemangioblastomas, and lesions in the kidneys, pancreas, and epididymis that characterize the syndrome. The prognosis of individuals with VHL has improved due to better recognition of the syndrome and earlier detection of malignancies.

Clinical features

Renal cell carcinoma occurs both in VHL and sporadically, although it tends to be diagnosed earlier in individuals with VHL (Neumann et al., 1998). Common presenting symptoms include hematuria and flank pain, and these tumors are sometimes discovered via routine screening in asymptomatic VHL patients. In the past, bilateral renal tumors justified total nephrectomy, but the need for dialysis and transplantation has been postponed by the development of nephron sparing subtotal resection techniques (Steinbach et al., 1995; Walther et al., 1995). Once tumors are discovered, the patients should be followed with computed tomography every 6 months until the lesion reaches approximately 3 cm in size, at which time surgery should be considered (Maher & Kaelin, 1997).

REFERENCES
Chang, S., Meisel, J., Hancock, S., Martin, D., McManus, M. & Adler, J. (1998). Treatment of hemangioblastomas in von Hippel–Lindau disease with linear accelerator-based radiosurgery. Neurosurgery, 43: 28–35
Chauveau, D., Duvic, C., Chretien, Y. et al. (1996). Renal involvement in von Hippel–Lindau disease. Kidney International, 50: 944–951
Choyke, P., Glenn, G., Walther, M., Patronas, N., Linehan, W. & Zbar, B. (1995). Von Hippel–Lindau disease: genetic, clinical, and imaging features. Radiology, 194: 629–642
Choyke, P., Glenn, G., Wagner, J. et al. (1997). Epididymal cystadenomas in von Hippel–Lindau disease. Urology, 47: 926–931
Eisenhofer, G., Lenders, J., Linehan, W., Walther, M., Goldstein, D. & Keiser, H. (1999). Plasma normetanephrine and metanephrine for detecting pheochromocytoma in von Hippel–Lindau disease and multiple endocrine neoplasia type 2. New England Journal of Medicine, 340: 1872–1879
Grossniklaus, H., Thomas, J., Vignesswaran, D. & Jarrett, W. (1992). Retinal hemangioblastoma. A histologic, immunohistochemical, and ultrastructural evaluation. Ophthalmology, 99: 140–145
Hes, F. & Feldberg, M. (1999). Von Hippel–Lindau disease: strategies in early detection (renal, adrenal, pancreatic masses). European Radiology, 9: 598–610
Hes, F., Luijt, R. & Lips, C. (2001). Clinical management of Von Hippel–Lindau (VHL) disease. Netherlands Journal of Medicine, 59: 225–234
Iliopoulos, O. & Kaelin, W. (1997). The molecular basis of von Hippel–Lindau disease. Molecular Medicine, 3: 289–293
Kempermann, G., Neumann, H. & Volk, B. (1998). Endolymphatic sac tumours. Histopathology, 33: 2–10
Krieg, M., Marti, H. & Plate, K. (1998). Co-expression of erythropoietin and vascular endothelial growth factor in nervous system tumors associated with von Hippel–Lindau tumor suppressor gene loss of function. Blood, 92: 3388–3393
Latif, F., Tory, K., Gnarra, J. et al. (1993). Identification of the von Hippel–Lindau disease tumor suppressor gene. Science, 260: 1317–1320
Lindau, A. (1927). Aur Frage der Angiomatosis retinae und ihrer Hirnkomplikationen. Acta Ophthalmologica, 4: 193–226
Lubensky, I., Gnarra, J., Bertheau, P., Walther, M., Linehan, W. & Zhuang, Z. (1996). Allelic deletions of the VHL gene detected in multiple microscopic clear cell renal lesions in von Hippel–Lindau disease patients. American Journal of Pathology, 149: 2089–2094
Maher, E. & Kaelin, W. (1997). Von Hippel–Lindau disease. Reviews in Molecular Medicine, 76: 381–391
Maher, E., Yates, J. & Ferguson-Smith, M. (1990a). Statistical analysis of the two stage mutation model in von Hippel–Lindau disease, and in sporadic cerebellar haemangioblastoma and renal cell carcinoma. Journal of Medical Genetics, 27: 311–314
Maher, E., Yates, J., Harries, R. et al. (1990b). Clinical features and natural history of von Hippel–Lindau disease. Quarterly Journal of Medicine, 77: 1151–1163
Maher, E., Iselius, L., Yates, J. et al. (1991). Von Hippel–Lindau disease: a genetic study. Journal of Medical Genetics, 28: 443–447
Neumann, H., Bender, B., Berger, D. et al. (1998). Prevalence, morphology and biology of renal cell carcinoma in von Hippel–Lindau disease compared to sporadic renal cell carcinoma. Journal of Urology, 160: 1248–1254
Neumann, H., Bender, B., Reincke, M., Eggstein, S., Laubenberger, J. & Kirste, G. (1999). Adrenal-sparing surgery for phaeochromocytoma. British Journal of Surgery, 86: 94–97
Patrice, S., Sneed, P., Flickinger, J. et al. (1996). Radiosurgery for hamangioblastoma: results of a multi-institutional experience. International Journal of Radiation Oncology Biology Physics, 35: 493–499
Richard, S., Campello, C., Taillandier, L., Parker, F. & Resche, F. (1998). Haemangioblastoma of the central nervous system in von Hippel–Lindau disease. Journal of Internal Medicine, 243: 547–553
Richard, S., David, P., Marsot-Dupuch, K., Giraud, S., Beroud, C. & Resche, F. (2000). Central nervous system hemangioblastomas, endolymphatic sac tumors, and von Hippel–Lindau disease. Neurosurgery Review, 23: 1–22
Seizinger, B., Rouleau, G., Ozelius, L. et al. (1998). Von Hippel–Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma. Nature, 332: 268–269
Steinbach, F., Novick, A., Zincke, H. et al. (1995). Treatment of renal cell carcinoma in von Hippel–Lindau disease: a multicenter study. Journal of Urology, 153: 1812–1816
Hippel, E. (1904). Ueber eine sehr seltene Erkrankung der Nethaut. Graefes Archives of Ophthalmology, 59: 83–106
Walther, M., Choyke, P., Weiss, G. et al. (1995). Parenchymal sparing surgery in patients with hereditary renal cell carcinoma. Journal of Urology, 153: 913–916
Walther, M., Keiser, H., Choyke, P., Rayford, W., Lyne, J. & Linehan, W. (1999). Management of hereditary pheochromocytoma in von Hippel–Lindau kindreds with partial adrenalectomy. Journal of Urology, 161: 395–398
Werness, B. & Guccion, J. (1997). Tumor of the broad ligament in von Hippel–Lindau disease of probable Mullerian origin. International Journal of Gynecological Pathology, 16: 282–285
Wittebol-Post, D., Hes, F. & Lips, C. (1998). The eye in von Hippel–Lindau disease. Long-term follow-up of screening and treatment: recommendations. Journal of Internal Medicine, 243: 555–561
Zbar, B., Kishida, T., Chen, F. et al. (1996). Germline mutations in the Von Hippel–Lindau disease (VHL) gene in families from North America, Europe, and Japan. Human Mutation, 8: 348–357