Von Hippel-Lindau (VHL) syndrome, also known as Von Hippel-Lindau disease, is a rare genetic disorder that causes the development of multiple benignnot cancerous, can grow but will not spread to other body parts (non-cancerous) and malignantcancerous, may grow and spread to other areas of the body (cancerous) tumoura tissue mass that forms from groups of unhealthy cells throughout the body. It is caused by a mutation to the Von Hippel-Lindau gene, which is a tumour suppressor gene located on chromosome three.
Familial cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs syndromes, also known as hereditary cancer syndromes, are rare conditions that cause an increased riskthe possibility that something bad will happen of cancer as the result of inherited genetic mutations in certain cancer-related genes. They can affect both adults and children, however they generally develop in people at a younger age than normal. While familial cancer syndromes are not classified as cancer, they are equally as severe and can be life-threatening as they are associated with the development of various tumours throughout the body. Having a familial cancer syndrome does not guarantee the development of cancer, however the risk of developing cancer is higher than those who do not have a familial cancer syndrome.
VHL tends to affect the sexes equally, and is generally diagnosed around the age of 26. However, anyone can get this disease.
Types of Von Hippel-Lindau
VHL can be categorised into five subtypes, based on the likelihood of developing certain types of tumours.
Type 1A Von Hippel-Lindau
Type 1A VHL is characterised by low risk of developing pheochromocytomas, but higher risk for developing RCC, haemangioblastoma of the central nervous system (CNS), pancreatic cystsabnormal growths that are usually filled with liquid or air, and pNETs.
Type 1B Von Hippel-Lindau
Type 1B VHL is characterised by low risk of developing pheochromocytomas and RCCs, but higher risk for developing CNS haemangioblastomas, pancreatic cysts, and pNETS.
Type 2A Von Hippel-Lindau
Type 2A VHL is characterised by low risk of RCC, but high risk for pheochromocytomas. This may occur with or without the development of the other tumours listed above.
Type 2B Von Hippel-Lindau
Type 2B VHL is characterised by high risk for pheochromocytoma and RCC. This may occur with or without the development of the other tumours listed above.
Type 2C Von Hippel-Lindau
Type 2C VHL is characterised by high risk for pheochromocytoma, with or without the risk the risk of RCCs and haemangioblastomas.
Von-Hippel Lindau Related Tumours
VHL is most commonly associated with the development of haemangioblastomas, however it has also been linked to other types of tumours. Some examples include:
- Haemangioblastoma.
- Renal cell carcinoma (RCC).
- Pheochromocytoma.
- Paraganglioma.
- Pancreatic neuroendocrine tumours (NETs), potentially including:
- Endolymphatic sac tumours.
Treatment
When cancers are detected, they are staged and graded based on size, metastasiswhen the cancer has spread to other parts of the body, also known as mets, and how the cancer cellsthe basic structural and functional unit of all living things look under the microscope. Stagingthe process of determining how big the cancer is, where it started and if it has spread to other areas and grading helps your doctors determine the best treatment for you. However, each patient with VHL will present with a unique disease behaviour, with varying tumour locations and symptoms. As such, there is no one treatment method that will work for everyone, and there is no standard staging system for this disease. Instead of staging and grading, your doctor will recommend a treatment plan based on the following factors:
- Type of tumours present.
- Whether the tumours are malignant (cancerous) or benign (non-cancerous).
- Tumour location.
- Whether or not malignant tumours have metastasised.
- Your age.
- General health.
- Your treatment preferences.
Your doctor may also recommend genetic testinga procedure that analyses DNA to identify changes in genes, chromosomes and proteins, which can be used to analyse tumour DNA to help determine which treatment has the greatest chance of success, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you.
Treatment options for tumours associated with VHL may include:
- Surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence to remove as much of the tumour(s) as possible – this will vary based on tumour location.
- Radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells.
- Chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells.
- Ablation therapya minimally invasive procedure that uses extremely high or low temperatures to destroy (ablate) abnormal tissue and/or cancer cells.
- Clinical trialsresearch studies performed to test new treatments, tests or procedures and evaluate their effectiveness on various diseases.
- Palliative carea variety of practices and exercises used to provide pain relief and improve quality of life without curing the disease.
Cancer Screening
Once a diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results of VHL has been confirmed, implementing a targeted screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening plan becomes essential due to the increased risk of developing certain cancers. The content of this plan will vary from person to person based on the genetic mutation involved, your family’s history of cancer and the types of cancers that may be present. It will also outline the routine tests you should have and how regularly you should have them. Some recommendations for VHL may include:
- Annual physical examinationan examination of your current symptoms, affected area(s) and overall medical history starting before the age of 10.
- Annual neurological examinationan assessment of sensory and motor functions, such as vision, balance and coordination starting before the age of 10.
- Annual bloodthe red bodily fluid that transports oxygen and other nutrients around the body pressure measurement starting before the age of 10.
- MRI of the brain and spine every two years starting at age 11.
- Annual eye exam starting at the age of one.
- Abdominal MRI assessing the kidneys, pancreasa long, flat organ that sits between the stomach and the spine that plays a key role in digestion and blood sugar regulation and adrenal glands every two years starting at the age of 15.
- Annual measurement of metanephrine levels (either via a 24-hour urine test or a blood test) starting at age five.
- Hearing assessment every 2-3 years starting at age 11 – annually if symptoms of hearing loss, vertigodizziness, a sensation of spinning or moving and/or tinnitusringing in one or both ears are present.
- MRI of the internal auditory canals in asymptomatic people between the ages of 15-20 or as soon as symptoms of hearing loss, vertigo and/or tinnitus are present.
Screening options for VHL may evolve as new technologies are developed and our understanding of the condition grows. It is essential to discuss your individual circumstances with your healthcare team to determine the most appropriate screening plan for you.
Risk factors
VHL is caused by a genetic mutation in the VHL gene, which acts as a tumour suppressor in the body. It is an autosomal dominant disease, which means you have a 50% chance of developing the condition if one of your parents carries the mutation.
Symptoms
The symptoms of VHL often vary by the type(s) of tumours present. General symptoms of VHL may include:
- Difficulties with balance and/or coordination.
- Impaired vision.
- Muscle weakness and/or pain in the affected area.
- Headaches.
- Back aches.
- Neck pain.
- Impaired bowelportion of the digestive system that digests food (small bowel) and absorbs salts and water (large bowel); also called intestines and/or bladdera hollow, muscular sac in the pelvis that stores urine function.
- Numbness and/or tingling in affected areas.
- Haematuriathe presence of blood in urine.
- Unexplained weight loss/loss of appetite.
- Fatiguea state of extreme tiredness or exhaustion, can be physical or mental.
- Fevers.
- Hypertensionhigh blood pressure.
- Unexplainable sweatiness.
- Tachycardiaa rapid heart rate; clinically defined as a rate of more than 100 beats per minute.
- Hearing loss.
- Tinnitus (ringing in the ears).
- Vertigo (dizziness).
Symptoms related to specific tumours can be found on our knowledgebase.
Not everyone with the symptoms above will have cancer, but see your general practitioner (GP) if you are concerned.
Diagnosis
If your doctor suspects you have tumours associated with VHL, they may order some of the following tests to confirm the diagnosis and refer you to a specialist for treatment. The tests required for diagnosis will often vary based on the symptoms present, and where the tumour(s) are suspected to be located.
- Physical examination.
- Genetic testing.
- Neurological examination.
- Eye examination.
- Endocrine studiesstudies that involve blood, urine and/or imaging tests to analyse hormone levels.
- Imagingtests that create detailed images of areas inside the body tests, potentially including:
- MRI (magnetic resonance imaging)a type of medical imaging that uses radiowaves, a strong magnet and computer technology to create detailed images of the body.
- CT (computed tomography) scana type of medical imaging that uses x-rays and computer technology to create detailed images of the body.
- PET (positron emission tomography) scana type of medical imaging that uses radioactive tracers to create detailed images of the body.
- Ultrasounda type of medical imaging that uses soundwaves to create detailed images of the body .
- Exploratory procedures, such as an endoscopya procedure that involves inserting a long, flexible tube with a light and small camera (endoscope) into the body to view internal organs.
- Biopsyremoval of a section of tissue to analyse for cancer cells.