People with vhl also have an increased risk of developing clear cell renal cell. Genetic testing for hereditary mutations in the vhl gene. Prevalence of vhl disease is estimated to be between one of 3 and one of 53000 1. Hemangioblastomas that develop in the brain and spinal cord can cause headaches, vomiting, weakness, and a loss of muscle coordination ataxia. 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%. Although vhl disease can have serious complications, if these are detected early they can usually be treated successfully. Vhl syndrome is characterized by the presence of benign and. Four germline tumors in this young patient, and in a second, older patient with vhl syndrome demonstrate minimal intratumor heterogeneity and mutational burden, and evaluable tumors appear to follow a linear evolutionary route, compared to tumors from patients with. For individuals with vhl syndrome, those with a vhl pathogenic variantand atrisk relatives of unknown genetic status. Handbook of genetic counselingvon hippellindau syndrome. The data from all vhl families were analyzed additional file 1.
In this comprehensive study of east asian patients, we investigated the. Pdf pvon hippellindau syndrome vhl is a familial neoplastic condition seen in approximately 1 in 36000 live births. It was recently found that homozygosity for the vhl arg200trp mutation is. Retinal vascular proliferation as an ocular manifestation. Research open access development of synchronous vhl. Association of vhl genotype with pancreatic neuroendocrine. If you have problems viewing pdf files, download the latest version of adobe reader. The tumor was located in the lower anterior pole of the right kidney and was bisected to give two tumor regions. Four germline tumors in this young patient, and in a second, older patient with vhl syndrome demonstrate minimal intratumor heterogeneity and mutational burden, and evaluable tumors appear to follow a linear evolutionary route, compared to tumors from patients with sporadic clear cell renal cell carcinoma. Slowgrowing hemgioblastomas benign tumors with many blood vessels may develop in the brain, spinal cord, the. Here we report a 42yearold woman who had been operated for cerebellar hemangioblastoma and. It is caused by germline mutations of the tumor suppressor gene vhl, located on. But some tumors, such as those in the kidney and pancreas, can become cancerous. 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 disease is a hereditary cancer syndrome charac. Als er klachten zijn van gehoorverlies of oorsuizen is aanvullend onderzoek nodig mri scan. Genetic testing for hereditary mutations in the vhl gene that. We report a caucasian male with a family history of pheochromocytoma and the.
Synonymous mutations are expected to be phenotypically silent and their role in vhl disease remains poorly understood. Previous studies suggested that similar populations of caucasian and japanese patients have similar genotype or phenotype characteristics. Vhl disease effects 1 in 36,000 people 10,000 cases in the u. The past several years, we have stretched that number to 7580. Vhl disease is different in every patient, even within the same family. Age, ysexa basis of vhl disease diagnosis vhl gene mutation, effect on vhl protein vhl family history systemic manifestations of vhl disease at most. Protocol to guide the testing for hereditary mutations in the. A germline mutation of this gene is the basis of familial inheritance of vhl syndrome. Vhl genetic testing table 22 diagnostic yield of genetic testing for vhl gene mutations in the diagnosis of. Vhl disease is caused by mutations in the vhl gene on chromosome the p arm of chromosome 3 3p25. Full text full text is available as a scanned copy of the original print version. 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. Fortunately, the morbidity and mortality caused by cns hemangioblastomas.
As an illustration, an interesting case is presented of a pregnant woman with refractory hypertension. The information in this outline was last updated in oct 2002. If you have not installed and configured the adobe acrobat reader on your system. Development of synchronous vhl syndrome tumors reveals. 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. In this small set of patients with early stage vhlassociated tumors, there is reduced mutation burden and limited evidence of intratumor heterogeneity. It proved to be the first manifestation of bilateral pheochromocytomas. In this comprehensive study of east asian patients, we investigated the genetic and clinical. Links to pubmed are also available for selected references. A further 11 patients showed pheochromocytoma and islet cell tumor. Tumors may be either noncancerous or cancerous and most frequently appear during young adulthood. 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.
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. Get a printable copy pdf file of the complete article 808k, or click on a page image below to browse page by page. Genetic and rare diseases information center gard po box 8126, gaithersburg, md 208988126 tollfree. 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. Not only are mutations in this gene responsible for the vhl syndrome, but mutations are also very frequent in sporadic rcc. This disease is often genetic and inherited in an autosomal dominant fashion, and can present in.
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. 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. Tumors in vhl include hemangioblastomas, which are blood vessel tumors of the brain, spinal cord, and eye. It is relatively recent that type 2c was identified as a separate group solely presenting with pheochromocytomas. Extraadrenal pheochromocytomas are termed paragangliomas. It can affect several different parts of the body and cause several types of problems. In either situation, hemangioblastomas can cause significant morbidity and mortality through mass effect on nearby structures 1, 7, 25, 32. 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. Vhl is characterised by highly vascularised tumours in different organs. Vhl disease is an autosomal, dominant inherited tumour syndrome with an estimated prevalence of 23 patients per 100,000 persons. Some rare patients with vhl syndrome have polycythemia, which has been attributed to epo production by a tumor. They can grow in your brain and spinal cord, kidneys, pancreas, adrenal glands, and reproductive tract. Protocol to guide the testing for hereditary mutations in.
Hemangioblastomas benign, or noncancerous, tumors made up of nests of blood vessels of the brain and spine. Vhl is a tumour suppressor gene on the short arm of chromosome 3. Vhl syndrome is an autosomal dominant disorder predisposing to the development of tumors, due to inherited mutations in the vhl gene. Mutations in the vhl gene in sporadic apparently congenital. An unusual presentation of glomeruloid hemangioma in a. It is named after the two doctors who described it. This test requires physician attestation that patient consent has been received.
Paragangliomas in the mediastinum, especially the superior mediastinum, are extremely rare. 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. 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. It is characterized by visceral cysts and benign tumors with potential for subsequent malignant transformation. Hemangioblastomas can also occur in the lightsensitive tissue that lines the back of the eye the retina. 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. The active surveillance guidelines focus on searching for manifestations that are often problematic. Pathogenic vhl mutations include deletion, frameshift, nonsense and missense mutations.
584 1429 1213 627 772 965 1485 716 804 428 638 335 1232 546 252 1194 1019 1183 1087 179 1487 203 300 1273 711 1200 1496 49 420 401 1464 413 66 1279