For VHL Warriors
Having a rare disease like VHL can be very tough and challenging. We understand that being affected by VHL can also be lonely, but you are not alone! The VHL Warriors page offers support and guidance into navigating this chronic illness as well as provides the means to connect other VHL warriors together to create a community. The goal is to equip you with the tools and resources to boost resilience, accessing care for VHL, understanding VHL, and ultimately increase the feeling of control. This is a reminder that you are not alone.
About VHL
The discovery of von Hippel-Lindau Disease is attributed to the work of many scientists starting as early as 1864. The two main contributors were Eugine von Hippel a German ophthalmologist and Avrid Lindau a Swedish pathologist. von Hippel first found a pattern of tumors on the retina in 1904, and in 1927 Lindau identified a trend of brain and spinal tumors. It 1936 research brought this information together and called it “von Hippel-Lindau” disease.
Origin of the Disease
von Hippel-Lindau Disease (VHL) is in most cases an inherited disorder in an autosomal dominant pattern. It is a mutation on the third chromosome which is known as the tumor repressor gene. This disease presents as the growth of tumors or cysts (which are fluid filled sacs) in various areas of the body. The areas most often effected are the eyes, lower part of the brain, spine, kidneys, pancreas and adrenal glands. The mutation on the third chromosome prohibits cells to interpret information properly. The cells act as if they do not have enough oxygen and as a result the cells around the affected cell start producing abnormally high levels of blood vessels creating tumours and cysts. In VHL, the tumors are often benign depending on the location. The harm comes when they grow to excess and damage surrounding organs. Tumours found on the kidney or pancreas are more likely to be cancerous.
“The de novo (new) mutation occurred in the germ cell (sperm or egg) or the young embryo before a process called cell differentiation. As the embryo grew, this new mutation replicated over and over again. Thus this person will have a mutation in the VHL gene in every cell of their body which can be identified via a genetic test. Although there is no family history of VHL, the person will still have a 50% chance of passing it on to their children.”
VHL Patient Survey Results
In December 2022 CVHL conducted an online survey of patients and caregivers to assess the challenges VHL patients and caregivers face because of the disease. This information was utilized in the February 2023 CADTH and INESSS submissions supporting provincial and territorial funding of Belzutifan (Welireg).
123 patients and caregivers participated in the survey.
How is VHL Diagnosed?
Early diagnosis is the key to the providing people living with VHL disease with the best care and most effective treatment. When there is a known family history, it is important to conduct DNA testing as soon as possible to determine if the patient has VHL disease, regardless if the person currently has a tumor or presents with symptoms.
If there is a positive DNA diagnoses of VHL, it is important to begin surveillance testing early before any symptoms occur, if possible. Most VHL lesions are easier to treat when they are small. Detection of affected individuals by DNA analysis of a blood sample is now possible for nearly all VHL families. The accuracy of the testing and its usefulness in most families is increasing rapidly. DNA testing can be used to determine which members of the family need to be followed closely. It can also determine which members may be reassured that they they do not carry the VHL gene mutation.
If genetic testing is not yet available for a suspected VHL mutation, an individual may be clinically diagnosed, based on the onset of symptoms (ie. detected lesions), and will need to continue with regular medical screening. One set of normal results or findings does not necessarily mean there is no VHL present, since the first evidence of VHL may occur later in life. Occasionally a person may be so mildly affected that VHL may seem to skip a generation. VHL has been diagnosed for the first time in people as old as 80, often because their children or grandchildren developed VHL tumours.
Eighty percent of individuals affected by VHL have inherited the mutated tumor suppressor gene, with a fifty percent chance of passing that mutated gene to their offspring. The remaining twenty percent of those with VHL are a result of a spontaneous mutation, or a mosaic presentation. Genetic diagnosis is more complex as the VHL mutation may be absent from blood and the genetic test can be falsely negative.
Types of VHL
Four general VHL disease phenotypes have been suggested based on the likelihood of the type of tumors that have been presented in patients. They include; Type 1, Type 2, Type 2A, Type 2B, and Type 2C.
There has been some material research that supports the conclusion that phaeochromocytomas appear to be distinct from other VHL lesions. Therefore, the most relevant correlations rely on the presence or absence of phaeochromocytomas in a patient. As research continues in this area, we are learning more, please note that patterns are not clear-cut, and correlations have no current diagnostic or therapeutic value and are used for academic purposes at the present time. Our goal is to support research like this to understand the quality of life and preventative health implications for patients.
VHL Type 1
Presents with retinal angioma, CNS hemangioblastoma, renal cell carcinoma, pancreatic cysts and neuroendocrine tumors. This type is characterised by a low risk for phaeochromocytoma.
VHL Type 2
Presents with phaeochromocytoma, retinal angioma and CNA hemangioblastomas. This type is characterized by a high risk for phaeochromocytoma.
VHL Type 2 is further subdivided:
- Type 2A – Typically presents with phaeochromocytoma, retinal angioma and CNS hemangioblastomas, low risk for renal cell carcinoma
- Type 2B – Typically presents with phaeochromocytoma, retinal angioma, CNS hemangioblastomas, pancreatic cysts and neuroendocrine tumor with a high risk for renal carcinoma
- Type 2C – Typically risk for phaeochromocytoma only
Questions & Answers
How common is VHL?
VHL Disease is rare. It occurs in about 1 in 36,000 births. Both women and men can have it. Most cases of VHL Disease are inherited (passed down) from a parent, but about 20% of individuals with VHL are the first members of their family to have the disease.
What is involved in DNA testing?
This is just a simple blood test that is typically completed in the genetics department of your hospital.The results typically take 14-21 days to completion.
What does a negative VHL DNA test result mean?
A negative VHL mutation can be indicated for a few reasons:
- You may not have the mutation at all but the gene is in your family
- You may have a mutation in a different gene that causes VHL like disease. Other diseases share similar features with VHL diseases. Other hereditary diseases can cause kidney cancer or renal cell carcinoma. Your genetic counsellor may recommend testing for other syndromes.
- The VHL presentation may have been a spontaneous mutation (not inherited), and may not show in every cell of your body, causing a negative result, when another test may show a positive result.
If I have the VHL gene, what are the risks to my children?
If you have the VHL mutation, each of your children will have a one in two chance of inheriting the gene. A child who inherits the mutated VHL gene would inherit the risks associated with it. However, the same mutation may cause different problems, or not cause any problems, in different family members. It is a good idea for your children to have genetic counselling and consider genetic testing an an early age for preventative treatment.
What causes VHL?
VHL is caused by a mutated gene, the “suppressor gene” that is involved in preventing tumors from growing in the body. a mutated VHL gene can increase the chance that certain tumors will develop and cause VHL Disease. Mutations of the VHL supporessor gene can ge detected through DNA testing.
Who should get tested?
VHL genetic testing is generally recommended for the following:
- any individual with suspected VHL disease who does not meet clinical criteria
- any asymptomatic child with a parent known to have a pathogenic VHL mutation
- any individual with a family history of VHL disease
- any individual with a clinical diagnosis of VHL disease interesting in pursuing preimplantation genetic diagnosis or prenatal testing for this condition
What does a positive VHL test result mean?
A positive result means that mutation in the VHL gene was found. This means that you have an increased risk for developing certain features associated with VHL syndrome. The exact risks for VHL disease related tumors are not yet known, and vary from one person to another. Tumors may develop in the spine, the brain, the retina, kidney, pancreas and adrenal glands. There is also risk for tumors in the inner ears, liver cysts and benign tumors of the genital tract, the epidydimis in men and the broad ligament of the uterus in women.
If I have a VHL mutation, what are options for eliminating the gene for my children?
If you have the VHL mutation, you may want to learn about options for family planning. for example, embryos can be tested for the family’s genetic mutation before they are even implanted in a woman’s uterus. This process is called pre-implantation genetic diagnosis (PGD). This is performed in combination with an in-vitro fertilization (IVF), and may be an option for families who wish to have children without the hereditary cancer risk.
Become a Volunteer and Help Make Change
VHL is a rare disease, and we need your help to focus attention and awareness on VHL to the public.