Sequencing the vhl gene, improving diagnostics, limiting the removal of whole organs when there is a. Vhl is an autosomal dominant disorder, with a prevalence of around one in 36 000 and one in 50 000 live births 1, 2. Genotypephenotype correlations in vhl exon deletions. People with vhl syndrome are also at an increased risk for developing renal cell carcinoma rcc and pancreatic neuroendocrine tumors pnets. Lindau disease vhl is a hereditary multisystem cancer syndrome requiring lifelong prophylactic surveillance.
Current surveillance recommendations rely on best medical judgement and no evidence of effect exists. Recent evidence suggests that vhl may exhibit genetic anticipation ga. It predisposes affected individuals to the development of mainly 5 different types of neoplasms. Vhl alliance genetic and rare diseases information. Croft and others published vhl syndrome find, read and cite all the research you need on researchgate. 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. Inherited in an autosomal dominant manner, it arises from germline mutations in the vhl gene. 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. A genetic disease that is characterized by hemangioblastomas benign blood vessel tumors in the brain, spinal cord, and retina.
Aug 23, 2018 please use one of the following formats to cite this article in your essay, paper or report. Vhl syndrome is inherited in an autosomal dominant manner and is caused by a change that affects the vhl gene, a tumorsuppressor gene, on chromosome 3. This community is sponsored by the vhl alliance, an. In cases of vhl disease undergoing annual surveillance, the early detection and treatment pathways for symptomatic retinal. Vhl disease is an autosomal, dominant inherited tumor syndrome with an estimated prevalence of 23 per 100,000 persons omim no. A germline mutation of this gene is the basis of familial inheritance of vhl syndrome. A focused 35minute whole body mri screening protocol for. E3 ubiquitin ligases, which bind protein targets, leading to their ubiquitination and subsequent degradation, are attractive drug targets due to their exquisite substrate specificity. The vhl alliance support community connects patients, families, friends and caregivers for support and inspiration. Vhl syndrome is an autosomal dominant disorder with a high penetrance almost complete by 60 years of age characterized by. Tumors in vhl include hemangioblastomas, which are blood vessel tumors of the brain, spinal cord, and eye.
For individuals with vhl syndrome, those with a vhl pathogenic variant, and atrisk relatives of unknown genetic status, the most important intervention is surveillance. This community is sponsored by the vhl alliance, an inspire trusted partner. Hemangioblastomas benign, or noncancerous, tumors made up of nests of blood vessels of the brain and spine. The aim of this study was to determine if ga occurs in vhl, and if telomere shortening may be a factor in ga. Different types of mutations manifest various clinical phenotypes, from benign to malignant tumours or coexisting cysts. The incidence of vhl disease has been estimated to be 1 in 36,000 live.
Thus, a gene mutation test is essential in the diagnosis of vhl syndrome. The endolymphatic sac tumors can diminish hearing, which is a key symptom of vhl syndrome. Lindau vhl syndrome is a dominantly inherited familial cancer syndrome caused by mutations in the vhl gene. Affected patients develop central nervous system hemangioblastomas and abdominal tumors, among other lesions.
Vhl gene sequence analysis will reveal the pathogenic mutation 72% of the time. Genetic and rare diseases information center gard po box 8126, gaithersburg, md 208988126 tollfree. Vhl syndrome displays marked variation in expression and analysis of genotypephenotype correlations have led to the concept of four subtypes of vhl syndrome types 1, 2ac. Approximately 503 kinds of vhl gene mutations have been reported. Patients undergo an annual clinical screening program including separate magnetic resonance imaging mri of the brain, whole spine and abdomen. It is caused by germline mutations of the tumor suppressor gene vhl, located on. Molecular basis of the vhl hereditary cancer syndrome. We aimed to construct a more valuable genotypephenotype correlation based on alterations in. Individuals with vhl syndrome inherit one mutation in the vhl protein that causes. Vhl syndrome is characterized by the dominantly inherited predisposition to develop tumors of the central nervous system, kidney, retina, pancreas, and adrenal gland. Tumors may be either noncancerous or cancerous and most frequently appear during young adulthood.
Hemangioblastomas can also occur in the lightsensitive tissue that lines the back of the eye the retina. It is caused by germline mutations of the tumor suppressor gene vhl, located on the short arm of chromosome 3. As an illustration, an interesting case is presented of a pregnant woman with refractory hypertension. A germline mutation in the vhl gene predisposes carriers to tumors in multiple organs.
It is relatively recent that type 2c was identified as a separate group solely presenting with pheochromocytomas. Hemangioblastomas that develop in the brain and spinal cord can cause headaches, vomiting, weakness, and a loss of muscle coordination ataxia. A further 11 patients showed pheochromocytoma and islet cell tumor. Association of vhl genotype with pancreatic neuroendocrine. For language access assistance, contact the ncats public information officer. The most common pathological lesions are hemangioblastomas of the central nervous system, retinal angiomas, renal clear cell carcinomas, and pheochromocytomas. A vhl database study supported by the vhl alliance was recently published from toronto canada pmid 3682. Vhl disease effects 1 in 36,000 people 10,000 cases in the u. These children have no history of the syndrome in their family. Current surveillance recommendations rely on best medical judgement and no.
Vhl mutations can lead to cellautonomous phenotypes in the tumor cells. Thus, a gene mutation test is essential in the diagnosis of vhl. Vhl is an autosomal dominant disorder, with a prevalence. Vhl syndrome is caused by germline mutations in the vhl tumor suppressor, and vhl tumors are associated with loss or mutation of the remaining wildtype allele. Slowgrowing hemgioblastomas benign tumors with many blood vessels may develop in the brain, spinal cord, the. Vhl mutations are the genetic defects underlying several human diseases including polycythemia, familial vhl tumor syndrome and sporadic renal cell carcinoma. As documented in the journal of medical genetics, the average life expectancy of someone with vhl has increased nearly 17 years. Loss of function variants in vhl are the only known cause of vhl, and germline vhl variants can be detected in up to 100% of vhl families. Dec 27, 2018 the hemangioblastomas in the retina can cause vision loss and may be the initial sign of vhl syndrome. Advances in the clinical world in the last century have dramatically improved the medical outcomes that vhl patients have. If you have problems viewing pdf files, download the latest version of adobe reader.
Evidence for genetic anticipation in vonhippellindau syndrome. It is characterized by visceral cysts and benign tumors with potential for subsequent malignant transformation. Vhl syndrome displays marked variation in expression and analysis of genotypephenotype correlations have led to the concept of four subtypes of. A germline mutation in the vonhippel lindau vhl gene predisposes carriers to development of abundantly vascularised. Inheritance is autosomal dominant with high penetrance and variable expression, and the condition is associated with inactivation of a tumor suppression gene located on chro. However, the development of smallmolecule inhibitors has proven extraordinarily challenging as modulation of e3 ligase activities requires the targeting of proteinprotein interactions.
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