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VHL Factsheet
| VHL Factsheet. |
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Von Hippel Lindau syndrome (V.H.L.) is named after two doctors who first recognised that some people, in the same family, manifested symptoms in different body organs which appeared to be connected.VHLS is an uncommon genetic disorder. Some had tumours (a tumour is an overgrowth of cells, it is not necessarily cancerous) in the retina of the eye, the kidneys,the hind quarter of the brain or cerebellum,the spinal cord, the pancreas and occasionally other organs. Angiomas(enlarged blood vessels) can occur in the retina, while haemangioblastomas may occur in the cerebellum or spinal cord. Kidney tumours or cysts are common and early detection of these kidney tumours is important .
Phaeochromocytomas occur in about 10%of patients, and endolymphatic sac tumours(causing deafness) occur in15%. Pancreatic and epididymal cysts are common, but rarely cause problems.
The presenting symptoms vary greatly in individual cases.This means that in different generations, or among siblings, affected individuals will not have the same organ affected: for example, one person may have an affected kidney, whilst in the other person the eyes are affected.
Early onset in childhood is infrequent but can occur, and surveillance should be started in the first few years of life.
Most people with VHLS develop clinical complications between the ages of 15 and 30 years, but in some cases no effects are noticed until after the age of 50 .Hence it is important that all individuals at risk are offered screening for subclinical involvement.
Detailed information and advice on screening and follow-up is available from your local genetic centre, and these are listed on our website.
The gene responsible for this disorder is on chromosome 3 and was identified in 1993.Pre-symptomatic diagnosis is available to most but not all families, by direct mutational analysis.VHLS is a dominant condition, but new mutations do occur.In these dominant conditions, if one of the parents is carrying the gene forVHLS on chromosome 3, each child has a 50/50 chance of inheriting the gene. Our genes are in pairs, and each parent will contribute one gene of each pair, to the baby when he or she is conceived. It is pure luck as to whether or not the good or faulty gene will be the one to be passed on. If the faulty gene is not passed on to an individual, that is the end of VHLS for that branch of the family. Genes do nor skip generations as is sometimes said.
If you or a family member have recently been diagnosed, all sorts of questions will occur to you .No doubt some of these will be frightening, and you will need all the information you can obtain.
As with lots of other medical conditions, V.H.L affects people differently, at differing ages and stages in their lives.
V.H.L is diagnosed in three different ways. If you have no symptoms, but another member of your family has the condition, you may have had a gene test. If the genetic mutation,(or faulty gene) has been identified in your family, then the test would be 100% accurate. If the test shows that you are carrying the gene for V.H.L. you will be offered screening, so that any signs or symptoms you may develop can be dealt with early, offering better outcomes. There are however still some families in which the gene has not been identified, and so a test would not be so accurate. Gene tests can be arranged through your Regional Genetic Centre, and your particular situation will be fully discussed in order to help you to make your decision.
You may have been showing signs and symptoms, and have been seen by a doctor who has made the diagnosis, taking into account your family history. Your doctors will discuss with you the most appropriate way of treating the condition in your particular case.
You may have been on a screening programme, and early signs of the condition have been detected.
You can help yourself by the usual means to healthy living, so that should you develop any of the manifestations of V.H.L. your body will be better able to deal with them. A healthy diet with lots of fruit and vegetables, plenty of rest, combined with exercise, and following the screening guidelines as recommended by your doctor all help to make you feel better. There is no cure for V.H.L. but in recent years much has been developed to make the outlook for patients more hopeful.
You will hear the word cancer applied to V.H.L. This is because V.H.L is one of a group of conditions known as hereditary cancer syndromes. This relates to kidney cancers in V.H.L. and not to the other cysts and haemangiomas affecting the eyes or brain. Very occasionally it is also found in the pancreas.
Prenatal diagnosis is not usually requested, but it is possible in families where the gene has been identified and a DNA. test can be done during pregnancy.
Unlike people in the general population, who may also develop cancers, you are in the situation of having them picked up and treated early, through screening; so your outlook should be better than that of a member of the general public .By saying this I do not wish in any way to minimise the degree of anxiety that V.H.L. people experience due to their condition.
When to tell the children, and should you consent to them having the gene test.
This is a question, which causes much heartache to parents. The gene test is offered so those children can be entered into appropriate screening programmes. Your doctor and genetic nurse, or associate will discuss this with you, and through the V.H.L. contact group you may be able to talk to other parents who have had to face this dilemma.
Telling prospective partners, explaining to friends and employers what V.H.L means to you, as an affected person can also be difficult. Through the contact group, perhaps I or others in the groups can help.
VHL is the subject of research in many parts of the world. This has already led to more effective screening, and appropriate treatment. The identification of the gene for VHL was a result of these endeavours. The ultimate aim is to find a cure, but this does not appear to be on the immediate horizon. It is good to know that scientist and doctors are active in this area, and that V.H.L. is not a backwater in this respect.
There is a V.H.L. Contact Group in the North West based in Manchester, run by myself. I am hopeful that similar groups will start in other areas of the country, and we will be able to extend our knowledge, and give more effective help to members.
My thanks to Eammonn Maher, Professor of Medical Genetics, University of Birmingham for updating this factsheet. September 2004.
Mary Weetman.
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| Action Medical Research 2007 |
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New diagnostic test for rare genetic condition
Von Hippel-Lindau disease is a genetic disorder which causes the insidious growth of cysts and tumours on many parts of the body, including the eyes, brain and kidneys. Sufferers stand a 50/50 chance of passing it onto their offspring, but until recently there was no way of determining whether or not someone had inherited the gene. Now, with help from Action Medical Research, a conclusive genetic test has been developed which brings an end to years of uncertainty for affected families.
The effects of Von Hippel Lindau (VHL) vary depending on where in the body the growths have developed, but they can cause a range of complications including headaches, blurred vision or blindness, unsteadiness, pain and even cancer. VHL affects more than 200,000 people globally, around 2,000 of whom are in the UK.
This variation in symptoms renders diagnosis difficult, yet early recognition of the syndrome and timely action can help prevent serious, often fatal, complications.
Before the development of the genetic test, doctors were unable to tell parents if their children had inherited the condition unless the characteristic cysts and tumours had started to occur. Patients and at-risk relatives were given regular screening tests to detect the complications, but this was expensive and time consuming, and non-sufferers spent years undergoing unnecessary, nerve-wracking testing, while those who had inherited the gene had no idea of how severe their symptoms might become.
The first step in developing a conclusive test was to identify where the faulty gene responsible for VHL lay. In 1991, an Action Medical Research grant was awarded to a team led by Professor Eamonn Maher at Cambridge University. In 1993, in collaboration with scientists in the USA, the breakthrough came – the gene for VHL was identified.
Next, with further Action Medical Research funding of £107,763, Professor Maher, now based at the University of Birmingham, and his team tackled the challenge of developing an accurate diagnostic test for the condition. They studied 142 families with VHL to find out what different mutations occurred. They also performed a range of tests on affected patients and their relatives to see if the variability in clinical symptoms was related to the type of mutation that they had. The team identified a whole range of VHL gene mutations, and used this data to develop methods for accurate genetic testing for the condition. They also identified genetic factors which predicted the likely severity of some of the clinical complications.
The genetic tests mean that once the faulty gene is identified in a patient, doctors can immediately set up regular screening sessions so the cysts and tumours that are likely to ensue can be picked up as early as possible. This way, if a complication does arise, action can be taken before the problem becomes more serious or life-threatening. Genetic testing can also give a prediction of the likely severity of some of the complications.
Action Medical Research has a long history of supporting genetic research, having helped to identify the genes for an inherited form of cleft lip and palate and the hereditary skin condition incontinentia pigmenti. In the 1970s the Charity also contributed to the building of the Institute of Medical Genetics in Glasgow, which is now one of the centres providing genetic testing for VHL.
The knowledge gained from studying this disease may have much wider benefits, particularly for cancer sufferers. A normal VHL gene is now known to produce a tumour suppressor protein which, when it functions, stops uncontrolled growth of cells which lead to tumours. Errors in the VHL gene are now also known to be associated with more common, non-inherited cancers, and with funding from Cancer Research UK, Professor Maher is investigating the implications of the VHL findings for cancerous conditions.
Taking Action for better health
- Genetic testing for VHL was introduced in the late 1990s as a direct result of this research.
- More than 20 centres across the UK are now offering the genetic test to VHL patients and their families.
- The West Midlands Regional Genetics Laboratory processes around 350 genetic tests for VHL each year. It is the largest centre for processing the results of these tests in the UK. (1)
- The cost of a single genetic test in 2006 was around £100-400(2)
- The cumulative costs of potentially unnecessary annual screening tests for family members, who may not even have the mutation, would be far greater, running into thousands of pounds.
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| Providing Answers for Families. |
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Providing answers for families
Tracey Fox-Stillwell and is all too familiar with the process of genetic testing for Von Hippel-Lindau. Her husband, Allen, was diagnosed with the condition in 2001, having inherited it from his mother, and since then three of their four daughters have been confirmed as carrying the VHL gene.
Tracey, explains, “Allen was diagnosed with the condition after having a brain tumour removed. Since then he has had a second tumour removed from his brain and been treated for growths on his retina and kidneys. At present he has four further brain tumours, three on his spine and multiple tumours on his kidneys.”
Despite the constraints that the condition places on Allen – he’s apprehensive about driving at night or with the family in the car, and suffers constant vertigo which often makes him ill – he remains positive. He continues to work full time as a self employed engineer, fitting in regular appointments with neurologists, urologists and ophthalmologists who monitor his condition.
Aware of the hereditary nature of VHL, the couple decided to have their daughters genetically tested to see whether the gene had been passed on to them. Tracey explains, “We chose the option of genetic testing for the family, as opposed to annual screening tests, because they give a straightforward answer. It would be far more stressful going to each screening appointment knowing you could be about receive bad news.”
Their tests were carried out at the University of Birmingham under the care of Professor Maher, beginning with their eldest daughter, eleven-year-old Tantara, in 2003. She received a positive result. A year later her nine-year-old sister, Ella, was also confirmed as carrying the gene, as was the couple’s youngest daughter Freya, age four, in 2006. The test showed that Ella’s twin sister, Mia, does not carry the gene. Although Ella and Freya are yet to show signs of the disease, Tantara is now active with VHL and already has 14 retinal tumours, for which she is receiving treatment.
Tracey says, “It was a big shock to be told that three of our daughters had the gene, but we were counselled before the tests and I think, in a way, we almost expected the results. We felt it was better to know – at least now the girls can grow up coming to terms with it from an early age, rather than being hit with it in their teens.
"They all took it very well. They can only go by Allen’s attitude towards the condition and he is so positive about the future that they are too.”
Following Tantara’s diagnosis the family set up a charity to raise money for more research into the condition. Tracey believes it helps the girls to see their friends and relations fundraising hard in the hope of finding a future cure.
Tracey believes the genetic testing has been a vital progression for families affected by VHL. “The test will save lives. Living with VHL relies on the early detection and treatment of growths, and knowing for sure that you’ve got the gene means that doctors can immediately offer the right medical care, rather than on a cautionary basis. As Allen says, ‘We’re lucky – we don’t have to wait for appointments and scans like other patients who do not even know what is wrong".
My thanks to Tracy and her family for allowing us to put this article on our website. Mary.
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