Vhl is an autosomal dominant disorder, with a prevalence of around one in 36 000 and one in 50 000 live births 1, 2. Dec 27, 2018 the hemangioblastomas in the retina can cause vision loss and may be the initial sign of vhl syndrome. Vhl is an autosomal dominant disorder, with a prevalence. If you have problems viewing pdf files, download the latest version of adobe reader. Slowgrowing hemgioblastomas benign tumors with many blood vessels may develop in the brain, spinal cord, the. The endolymphatic sac tumors can diminish hearing, which is a key symptom of vhl syndrome.
Vhl syndrome displays marked variation in expression and analysis of genotypephenotype correlations have led to the concept of four subtypes of. Vhl syndrome is a genetic condition caused by a mutation in one of two copies of the vhl gene. Hemangioblastomas benign, or noncancerous, tumors made up of nests of blood vessels of the brain and spine. Vhl disease effects 1 in 36,000 people 10,000 cases in the u. 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. Aug 23, 2018 please use one of the following formats to cite this article in your essay, paper or report. 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. Inherited in an autosomal dominant manner, it arises from germline mutations in the vhl 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.
Recent evidence suggests that vhl may exhibit genetic anticipation ga. The vhl alliance support community connects patients, families, friends and caregivers for support and inspiration. This community is sponsored by the vhl alliance, an. Association of vhl genotype with pancreatic neuroendocrine. It proved to be the first manifestation of bilateral pheochromocytomas. Current surveillance recommendations rely on best medical judgement and no evidence of effect exists. Approximately 503 kinds of vhl gene mutations have been reported. 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. For individuals with vhl syndrome, those with a vhl pathogenic variant, and atrisk relatives of unknown genetic status, the most important intervention is surveillance. A focused 35minute whole body mri screening protocol for. As an illustration, an interesting case is presented of a pregnant woman with refractory hypertension.
The most common pathological lesions are hemangioblastomas of the central nervous system, retinal angiomas, renal clear cell carcinomas, and pheochromocytomas. Individuals with vhl syndrome inherit one mutation in the vhl protein that causes. Lindau disease vhl is a hereditary multisystem cancer syndrome requiring lifelong prophylactic surveillance. Tumors may be either noncancerous or cancerous and most frequently appear during young adulthood. For language access assistance, contact the ncats public information officer. It is caused by germline mutations of the tumor suppressor gene vhl, located on the short arm of chromosome 3. Tumors in vhl include hemangioblastomas, which are blood vessel tumors of the brain, spinal cord, and eye. Vhl mutations can lead to cellautonomous phenotypes in the tumor cells. Thus, a gene mutation test is essential in the diagnosis of vhl syndrome. 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. Genotypephenotype correlations in vhl exon deletions.
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. Advances in the clinical world in the last century have dramatically improved the medical outcomes that vhl patients have. It predisposes affected individuals to the development of mainly 5 different types of neoplasms. We aimed to construct a more valuable genotypephenotype correlation based on alterations in. These children have no history of the syndrome in their family. Vhl gene sequence analysis will reveal the pathogenic mutation 72% of the time. Vhl alliance genetic and rare diseases information. It is characterized by visceral cysts and benign tumors with potential for subsequent malignant transformation. This community is sponsored by the vhl alliance, an inspire trusted partner. Molecular basis of the vhl hereditary cancer syndrome. Croft and others published vhl syndrome find, read and cite all the research you need on researchgate. Patients undergo an annual clinical screening program including separate magnetic resonance imaging mri of the brain, whole spine and abdomen.
The incidence of vhl disease has been estimated to be 1 in 36,000 live. A germline mutation in the vonhippel lindau vhl gene predisposes carriers to development of abundantly vascularised. Vhl disease is an autosomal, dominant inherited tumor syndrome with an estimated prevalence of 23 per 100,000 persons omim no. The aim of this study was to determine if ga occurs in vhl, and if telomere shortening may be a factor in ga. A genetic disease that is characterized by hemangioblastomas benign blood vessel tumors in the brain, spinal cord, and retina. Vhl mutations are the genetic defects underlying several human diseases including polycythemia, familial vhl tumor syndrome and sporadic renal cell carcinoma. A vhl database study supported by the vhl alliance was recently published from toronto canada pmid 3682. Evidence for genetic anticipation in vonhippellindau syndrome.
It is caused by germline mutations of the tumor suppressor gene vhl, located on. Vhl syndrome is characterized by the dominantly inherited predisposition to develop tumors of the central nervous system, kidney, retina, pancreas, and adrenal gland. Different types of mutations manifest various clinical phenotypes, from benign to malignant tumours or coexisting cysts. E3 ubiquitin ligases, which bind protein targets, leading to their ubiquitination and subsequent degradation, are attractive drug targets due to their exquisite substrate specificity. Current surveillance recommendations rely on best medical judgement and no. Thus, a gene mutation test is essential in the diagnosis of vhl. As documented in the journal of medical genetics, the average life expectancy of someone with vhl has increased nearly 17 years.
Genetic and rare diseases information center gard po box 8126, gaithersburg, md 208988126 tollfree. Vhl syndrome is an autosomal dominant disorder with a high penetrance almost complete by 60 years of age characterized by. A germline mutation of this gene is the basis of familial inheritance of vhl syndrome. In cases of vhl disease undergoing annual surveillance, the early detection and treatment pathways for symptomatic retinal. A further 11 patients showed pheochromocytoma and islet cell tumor. However, the development of smallmolecule inhibitors has proven extraordinarily challenging as modulation of e3 ligase activities requires the targeting of proteinprotein interactions. People with vhl syndrome are also at an increased risk for developing renal cell carcinoma rcc and pancreatic neuroendocrine tumors pnets. Intervention for most cns lesions remove brain and spinal lesions.
315 1521 1369 880 1303 924 1400 1441 1401 1540 1375 255 405 1539 901 1410 787 755 1566 950 323 283 1498 1326 664 1211 1582 405 1599 1321 201 1348 696 1268 1020 58 961 201 1339 1386 998 1267 630 760