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Von Hippel-Lindau Disease

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8 pages
A germline mutation in the Von-Hippel Lindau (VHL) gene predisposes carriers to development of abundantly vascularised tumours in the retina, cerebellum, spine, kidney, adrenal gland and pancreas. Most VHL patients die from the consequences of cerebellar haemangioblastoma or renal cell carcinoma. The VHL gene is a tumour suppressor gene and is involved in angiogenesis by regulation of the activity of hypoxia-inducible factor 1-α (HIF1-α). Clinical diagnosis of VHL can be confirmed by molecular genetic analysis of the VHL gene, which is informative in virtually all VHL families. A patient with (suspicion for) VHL is an indication for genetic counselling and periodical examination.
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Hereditary Cancer in Clinical Practice 2005; 3(4) pp. 171-178
Von Hippel-Lindau Disease
1 2 3 4 Frederik J. Hes , Jo W.M. Höppener , Rob B. van der Luijt , Cornelis J.M. Lips
1 2 Leiden University Medical Center, Center for Human and Clinical Genetics, Leiden; University Medical Center Utrecht, Department for Metabolic and Endocrine 3 4 Diseases; University Medical Center Utrecht, Division Biomedical Genetics; University Medical Center Utrecht, Department of Clinical Endocrinology
Key words: von Hippel-Lindau disease, VHL , genetics
Corresponding author: Frederik J. Hes, clinical geneticist, Leiden University Medical Center, Center for Human and Clinical Genetics, K5-R , PO Box 9600, 2300 RC , Leiden. Tel.: 071 526 8033, e -mail: f.j.hes@lumc.nl
This article was originally published in Dutch in the Dutch Journal of Oncology (Nederlands Tijdschrift voor Oncologie; N e d T i j d s c h r O n c o l 2 0 0 5 ; 2 ( 3 ) : 8 3 - 9 0 ) a n d i s r e p r i n t e d w i t h t h e p e r m i s s i o n o f A r i e z M e d i c a l P u b l i s h i n g, A m s t e r d a m , the Netherlands
Submitted: 5 November 2005 Accepted: 10 November 2005
Abstract
A germline mutation in the Von-Hippel Lindau (VHL) gene predisposes carriers to development of abundantly vascularised tumours in the retina, cerebellum, spine, kidney, adrenal gland and pancreas. Most VHL patients die from the consequences of cerebellar haemangioblastoma or renal cell carcinoma. The VHL gene is a tumour suppressor gene and is involved in angiogenesis by regulation of the activity of hypoxia-inducible factor 1- (HIF1-). Clinical diagnosis of VHL can be confirmed by molecular genetic analysis of the VHL gene, which is informative in virtually all VHL families. A patient with (suspicion for) VHL is an indication for genetic counselling and periodical examination.
Introduction
A germline mutation in the Von-Hippel Lindau (VHL) gene predisposes carriers to development of abundantly vascularised tumours in multiple organs. These tumours may include haemangioblastoma in the retina (also referred to as retinal angioma), cerebellum and myelum, renal cell carcinoma (clear cell type), phaeochromocytoma, islet cell tumours of the pancreas, and endolymphatic sac tumours, as well as cysts and cystadenoma in the kidney, pancreas, epididymis and broad ligament (Fig. 1) [1-3]. VHL disease is an autosomal, dominant inherited tumour syndrome with an estimated prevalence of 2-3 per 100,000 persons (OMIM #193300) [4]. At present,
metastases from renal cell carcinoma and neurological complications from cerebellar haemangioblastoma are the most common causes of death [5]. Using DNA diagnostics virtually all cases of classic VHL disease are identified, enabling early and presymptomatic diagnosis in families. Subsequently, periodical clinical examination and advanced operation techniques are likely to reduce both morbidity and mortality in patients with VHL disease.
Diagnostic criteria
In the presence of a positive family history, VHL disease can be diagnosed clinically in a patient with at least one