It was recently found that homozygosity for the vhl arg200trp mutation is. Paragangliomas in the mediastinum, especially the superior mediastinum, are extremely rare. 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. Fortunately, the morbidity and mortality caused by cns hemangioblastomas. Links to pubmed are also available for selected references. Slowgrowing hemgioblastomas benign tumors with many blood vessels may develop in the brain, spinal cord, the. It is caused by germline mutations of the tumor suppressor gene vhl, located on. Mutations in the vhl gene in sporadic apparently congenital. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a pdf plugin installed and enabled in your browser. If you have not installed and configured the adobe acrobat reader on your system. Research open access development of synchronous vhl. Vhl disease is a rare autosomal dominant inherited syndrome with high penetrance and variable expression, which involves inactivation of tumour suppressor gene on chromosome 3p25.
Not only are mutations in this gene responsible for the vhl syndrome, but mutations are also very frequent in sporadic rcc. It is named after the two doctors who described it. The clinical phenotype is characterized by the development of vascular tumors, including hemangioblastomas of the central nervous system and retina, clear cell renal cell carcinomas ccrccs and pheochromocytomas. 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.
The tumor was located in the lower anterior pole of the right kidney and was bisected to give two tumor regions. Hemangioblastomas benign, or noncancerous, tumors made up of nests of blood vessels of the brain and spine. The active surveillance guidelines focus on searching for manifestations that are often problematic. Pathogenic vhl mutations include deletion, frameshift, nonsense and missense mutations. In this small set of patients with early stage vhlassociated tumors, there is reduced mutation burden and limited evidence of intratumor heterogeneity. A further 11 patients showed pheochromocytoma and islet cell tumor. This process is difficult to follow and understand as events in a multitude of different genes can lead to similar outcomes without apparent cause. 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. Hemangioblastomas can also occur in the lightsensitive tissue that lines the back of the eye the retina. In this comprehensive study of east asian patients, we investigated the genetic and clinical.
A germline mutation of this gene is the basis of familial inheritance of vhl syndrome. Clinical and molecular characteristics of east asian. This test requires physician attestation that patient consent has been received. It is characterized by visceral cysts and benign tumors with potential for subsequent malignant transformation. As an illustration, an interesting case is presented of a pregnant woman with refractory hypertension. Handbook of genetic counselingvon hippellindau syndrome.
Genetic testing for hereditary mutations in the vhl gene that. Notice, the active surveillance guidelines do not include special monitoring of the reproductive tract, lung, and liver as these manifestations are often not a problem the emergency card that vhla encourages vhl patients to carry, focuses on signs and symptoms associated with vhl manifestations. Get a printable copy pdf file of the complete article 808k, or click on a page image below to browse page by page. Some rare patients with vhl syndrome have polycythemia, which has been attributed to epo production by a tumor. Synonymous mutations are expected to be phenotypically silent and their role in vhl disease remains poorly understood. The data from all vhl families were analyzed additional file 1.
Prevalence of vhl disease is estimated to be between one of 3 and one of 53000 1. Vhl is a tumour suppressor gene on the short arm of chromosome 3. The recent identification and characterization of the vhl gene on human chromosome 3p and mutational analyses confirms the vhl gene functions as a classical tumor suppressor. Vhl disease is an autosomal, dominant inherited tumour syndrome with an estimated prevalence of 23 patients per 100,000 persons. Vhl genetic testing table 22 diagnostic yield of genetic testing for vhl gene mutations in the diagnosis of. The past several years, we have stretched that number to 7580. They can grow in your brain and spinal cord, kidneys, pancreas, adrenal glands, and reproductive tract. Tumors in vhl include hemangioblastomas, which are blood vessel tumors of the brain, spinal cord, and eye. Association of vhl genotype with pancreatic neuroendocrine.
Vhl disease effects 1 in 36,000 people 10,000 cases in the u. The information in this outline was last updated in oct 2002. Als er klachten zijn van gehoorverlies of oorsuizen is aanvullend onderzoek nodig mri scan. An unusual presentation of glomeruloid hemangioma in a. Vhl disease is a hereditary cancer syndrome charac. Hemangioblastomas that develop in the brain and spinal cord can cause headaches, vomiting, weakness, and a loss of muscle coordination ataxia. Disease is predisposed by hemangioblastoma, renal cell carcinoma, pheochromocytoma, pancreatic islet cell and cystic tumors or epididymis tumors under the mutation or deletion at the tumor suppressor gene. Vhl syndrome is an autosomal dominant disorder predisposing to the development of tumors, due to inherited mutations in the vhl gene. Although vhl disease can have serious complications, if these are detected early they can usually be treated successfully. Genetic and rare diseases information center gard po box 8126, gaithersburg, md 208988126 tollfree. Vhl disease is different in every patient, even within the same family. Individuals with vhl syndrome inherit one mutation in the vhl protein that causes.
Vhl syndrome affects approximately 1 in 36,000 people worldwide and is characterised by both benign and malignant tumours in specific organs of the body including. Pdf pvon hippellindau syndrome vhl is a familial neoplastic condition seen in approximately 1 in 36000 live births. Genetic testing for hereditary mutations in the vhl gene. Tumors may be either noncancerous or cancerous and most frequently appear during young adulthood. This disease is often genetic and inherited in an autosomal dominant fashion, and can present in. Retinal vascular proliferation as an ocular manifestation.
Extraadrenal pheochromocytomas are termed paragangliomas. Previous studies suggested that similar populations of caucasian and japanese patients have similar genotype or phenotype characteristics. Protocol to guide the testing for hereditary mutations in the. Full text full text is available as a scanned copy of the original print version. It can affect several different parts of the body and cause several types of problems. Pdfs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%. For language access assistance, contact the ncats public information officer. Clinical and molecular characteristics of east asian patients. For individuals with vhl syndrome, those with a vhl pathogenic variantand atrisk relatives of unknown genetic status. Protocol to guide the testing for hereditary mutations in. Author summary cancer is generally caused by a series of mutations accumulating over time in a healthy tissue, which becomes reprogrammed to proliferate at the expense of the hosting organism. People with vhl also have an increased risk of developing clear cell renal cell. Vhl is characterised by highly vascularised tumours in different organs. Development of synchronous vhl syndrome tumors reveals.
But some tumors, such as those in the kidney and pancreas, can become cancerous. If you have problems viewing pdf files, download the latest version of adobe reader. Vhl syndrome is characterized by the presence of benign and. Here we report a 42yearold woman who had been operated for cerebellar hemangioblastoma and. Slowgrowing hemgioblastomas benign tumors with many blood vessels may develop in the brain, spinal cord, the retinas of the eyes, and near the inner ear. Vhl disease is caused by mutations in the vhl gene on chromosome the p arm of chromosome 3 3p25. It is relatively recent that type 2c was identified as a separate group solely presenting with pheochromocytomas.
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