The vhl gene is a tumour suppressor gene and is involved in angiogenesis by. Vhl disease is different in every patient, even within the same family. Vhl disease effects 1 in 36,000 people 10,000 cases in the u. Individuals with vhl syndrome inherit one mutation in the vhl protein that causes. Finding a cure for vhl will play a vital role in curing cancer. Mutations in one copy of the vhl gene can increase the chance for you to develop certain types of cancer in your lifetime. Early detection and treatment of tumors significantly improves a patients diagnosis. If you have not installed and configured the adobe acrobat reader on your system. Renal cell carcinoma, if the individual is younger than age 47 years or has a personal or family history of any other tumor typical of vhl. Diagnosis and management of ocular manifestations of vhl disease. A germline mutation in the vonhippel lindau vhl gene predisposes carriers to development of abundantly vascularised. Here, using an animal model of vhl, we report a marked improvement of vhlassociated phenotypes following treatment with hif2. Table 8 clinical and molecular subclassification of vhl disease 34 table 9 australian vhl screening protocol37 table 10 current mbs items related to detection of genetic mutations. Tumors may be either noncancerous or cancerous and most frequently appear during young adulthood.
For language access assistance, contact the ncats public information officer. The mean age of onset of vhl disease is 26 years, and 90% of affected individuals will show signs of the disease by age 65 years. The spectrum of clinical manifestations of the disease is broad and includes retinal and central nervous. Currently, there are no effective treatments available for vhl disease. Hemangioblastomas can also occur in the lightsensitive tissue that lines the back of the eye the retina. Although vhl disease can have serious complications, if these are detected early they can usually be treated successfully.
The vhl gene is ubiquitously expressed in normal tissues throughout the body. If you have problems viewing pdf files, download the latest version of adobe reader. In the cerebellar hemisphere, one patient had cystic hemangioblastoma of mural nodule type. The high fre quency of pvhl inactivation in renal cell carcinoma rcc makes it nearly universal to the disease state, and tumor suppression following reintroduction of vhl into. Synonymous mutations are expected to be phenotypically silent and their role in vhl disease remains poorly understood. Since it is impossible to predict exactly how and when the disease will present for each person, it is very important to check regularly for possible vhl manifestations throughout a persons lifetime. Vhl patients battle a series of tumours throughout their lives. An overview michele inglese, msn, rn, cnn,is clinical instructor, umdnj school of nursing, newark nj and staff nurse, hackensack university medical center, rutherford, nj. Hcs strategy targeting dysregulation of the vhlhif. We present this rare disease with discussion based on the literature. A germline mutation in the vonhippel lindau vhl gene predisposes carriers to development of abundantly vascularised tumours in the retina, cerebellum, spine, kidney, adrenal gland and pancreas. Hemangioblastomas that develop in the brain and spinal cord can cause headaches, vomiting, weakness, and a loss of muscle coordination ataxia. Although the incidence of vhl disease is low, affecting approximately 1 in 36 000 live births,1, 2 it is highly penetrant, as 95% of patients with characterized mutations in the vhl gene develop diseaserelated clinical manifestations by 60 years of age.
The vhl tumour suppressor gene comprises 3 exons and encodes two proteins, a full length 2 amino acid protein, which migrates with an apparent molecular weight of 2830 kda and a shorter 160 amino acid protein translated from an internal translation initiation site at codon 54. Two patients who had received a total resection of cerebellar hemangioblastoma developed cerebrospinal fluid dissemination during a longterm followup period. Preimplantation genetic diagnosis pgd for heritable neoplasia. The vhl gene is mutated in the commonest form of kidney carcinoma and in the germ line of patients with vhl. It is named after the two doctors who described it. Genetic and rare diseases information center gard po box 8126, gaithersburg, md 208988126 tollfree.
Vhl has been shown to be affected in more than 80 % of the ccrcc cases, either by allelic deletion, promoter methylation 19 %, or mutations 7080 %, 14. A germline mutation of this gene is the basis of familial inheritance of vhl syndrome. Slowgrowing hemgioblastomas benign tumors with many blood vessels may develop in the brain, spinal cord, the. But some tumors, such as those in the kidney and pancreas, can become cancerous. While these funds have not yet uncovered an effective pharmacological treatment for vhl, the supported research has resulted in approval of multiple cancer drugs for other cancers including kidney and breast cancers. Affected individuals are at increased risk of developing recurrent and bilateral kidney cysts and dysplastic lesions which may progress to clear cell renal cell carcinoma ccrcc. It is characterized by visceral cysts and benign tumors with potential for subsequent malignant transformation. They can grow in your brain and spinal cord, kidneys, pancreas, adrenal glands, and reproductive tract. Pathogenic vhl mutations include deletion, frameshift, nonsense and missense mutations. Given the multiple functions of pvhl the inactivation of vhl is a critical point in the initiation of tumor formation in the context of ccrcc 1517.
Transaxial nonenhanced and contrastenhanced ct scans through the cerebellum in a 34yearold patient with a family history of vhl. We report a caucasian male with a family history of pheochromocytoma and the. K ano and colleagues report the results of the analysis of a retrospective. Vhl disease is caused by mutations in the vhl gene on chromosome the p arm of chromosome 3 3p25. Retinal angioma, cns hemangioblastoma, renal cell cancer, pancreatic cysts. Since the identification of the vhl gene, at least 3 clinicalgenetic subtypes of the disease have been recognized objectives to identify the specific abnormality in the vhl gene and to correlate it with the prevalence and severity of ocular involvement in a large family with vhl disease. Genetic testing for hereditary mutations in the vhl gene. Disseminated cerebellar hemangioblastoma in two patients.
If the inline pdf is not rendering correctly, you can download the pdf file here. Before routine comprehensive screening, median survival of patients with vhl syndrome was less than 50 years lonser et al 2003. The vhl gene is involved in many other forms of cancer. Vhl tumour suppressor gene on the short arm of chromosome 3.
Protocol to guide the testing for hereditary mutations in. Although there is no cure for vhl, the associated tumors can be treated. Genetic testing also may helpful in diagnosing the disease. Retinal vascular proliferation as an ocular manifestation. Molecular characterization and ophthalmic investigation of.
Left untreated, vhl may result in blindness, permanent brain damage, or death. The use of molecular genetic testing for determining the genetic status of presumably atrisk relatives when a family enfefmedad with a clinical diagnosis of vhl syndrome is not available for testing is not straightforward. Vhl and are considered cornerstones among the clinical crite ria for the diagnosis of this. Individuals with vhl develop benign and malignant tumors including retinal and central. This gives further support for the proposal to associate the 547 t to c mutation with phenotype vhl 2a. Vhl disease is caused by monoallelic pathogenic variants in the vhl tumour suppressor gene which maps to. An unusual presentation of glomeruloid hemangioma in a. For individuals with vhl syndrome, those with a vhl pathogenic variantand atrisk relatives of unknown genetic status. Age, ysexa basis of vhl disease diagnosis vhl gene mutation, effect on vhl protein vhl family history systemic manifestations of vhl disease at most. Understanding your positive vhl genetic test result.
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