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