Von Hippel-Lindau (VHL) syndrome, also known as Von Hippel-Lindau disease, is a rare genetic disorder that causes the development of multiple benign (non-cancerous) and malignant (cancerous) tumour 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 cancer syndromes, also known as hereditary cancer syndromes, are rare conditions that cause an increased risk of cancer as the result of inherited genetic mutattions 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 is associated with the development of the tumours:
The type of tumour that develops can help classify the disease into five distinct subtypes.
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 cysts, and pNETs. Type 1 VHL may not have as good of a prognosis as type 2 VHL.
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 1 VHL may not have as good of a prognosis as type 2 VHL.
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 2 VHL often have a better prognosis that VHL type 1.
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 2 VHL often have a better prognosis that VHL type 1.
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. Type 2 VHL often have a better prognosis that VHL type 1.
Treatment
When cancers are detected, they are staged and graded based on size, metastasis (whether the cancer has spread to other parts of the body) and how the cancer cells look under the microscope. Staging and grading helps your doctors determine the best treatment for you. However, because VHL is not a cancer, the disease is generally not staged or graded. Instead of staging and grading, your doctor will recommend a treatment plan based on the following factors:
- Cancer location.
- Whether or not the cancer has metastasised.
- Your age.
- General health.
- Your treatment preferences.
Your doctor may also recommend genetic testing, 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 VHL often vary based on the type of tumours present. Generally, these options include:
- Surgery to remove as much of the tumour as possible.
- Radiation therapy, potentially including stereotactic body radiation therapy (SBRT) and peptide receptor radionuclide therapy (PRRT).
- Cryotherapy.
- Chemotherapy.
- Hormone medications.
- Targeted therapies.
- Watch and wait.
- Clinical trials.
- Palliative care.
For more information on the treatment options, please refer to the Rare Cancers Australia treatment options page.
Risk factors
While the cause of VHL remains unknown, the following factors may increase the likelihood of developing the disease:
- Having a family member with the disease.
- Having a genetic mutation of the VHL gene.
Not everyone with these risk factors will develop the disease, and some people who have the disease may have none of these risk factors. See your general practitioner (GP) if you are concerned.
Early symptoms
Symptoms of VHL often vary by the types of tumours present.
Symptoms of Hameangioblastomas
The symptoms of haemangioblastomas may include:
- Difficulties with balance.
- Impaired vision.
- Muscle weakness and/or pain in the affected area.
- Headaches.
- Back aches.
- Neck pain.
- Loss of coordination.
- Impaired bowel and/or bladder function.
- Numbness and/or tingling in affected areas.
Symptoms of Renal Cell Carcinomas
The symptoms of RCC include:
- Blood in the urine.
- Pain/dull aches in the side or lower back.
- Unexplained weight loss/loss of appetite.
- Fatigue.
- Fever.
- A lump in the kidney region.
Symptoms of Pheochromocytomas
The symptoms of pheochromocytoma may include:
- High blood pressure (hypertension).
- Headaches.
- Unexplainable sweatiness.
- Accelerated heart rate.
- Shakiness.
- Being very pale.
- Anxiety.
- Heart palpitations.
- An adrenal mass.
Some less common symptoms of pheochromocytoma include:
- Orthostatic hypotension (a form of low blood pressure that occurs when you stand up).
- Vision blurring.
- Unexplained weight loss.
- Frequent urination (polyuria).
- Constipation.
- Cardiomyopathy.
- Hyperglycaemia.
Symptoms of Paragangliomas
Parasympathetic paragangliomas are often asymptomatic and can be misdiagnosed or go undetected.
Sympathetic paragangliomas may present with some of the following symptoms:
- High blood pressure (hypertension).
- Headaches.
- Unexplainable sweatiness.
- Accelerated heart rate.
- Shakiness.
- Being very pale.
- Anxiety.
- Heart palpitations.
Symptoms of Endolymphatic Sac Tumours
The symptoms of endolymphatic sac tumours may include:
- Hearing loss.
- Tinnitus (ringing in the ears).
- Vertigo (dizziness).
- Facial paralysis, weakness and/or numbess.
Symptoms of Pancreatic Neuroendocrine Tumours (pNETs)
The symptoms of pNETs often vary by subtype:
Symptoms of Kidney Cysts
The symptoms of kidney cysts may include:
- Pain in your side, back or upper abdomen.
- Fevers and/or chills.
- Blood in your urine.
- Blocked blood or urine flow through your kidneys.
- Impaired kidney function.
- Abdominal pain.
- High blood pressure.
Symptoms of Pancreatic Cysts
The symptoms of pancreatic cysts may include:
- Abdominal bloating and/or pain.
- Nausea and/or vomiting.
- Unexplained weight loss/loss of appetite.
Not everyone with the symptoms above will have cancer, but see your general practitioner (GP) if you are concerned.
Diagnosis/diagnosing
If your doctor suspects you have VHL, they may order the following tests to confirm the diagnosis and refer you to a specialist for treatment.
Physical examination
Your doctor will collect your overall medical history, as well as your current symptoms. Following this, they may examine your body to check for any abnormalities.
Genetic testing
In addition to guiding treatment, genetic testing can be used to help diagnose certain conditions. Neurofibromatosis has been linked to mutations in the VHL gene, which changes specific protein functions. These changes can lead to cell abnormalities and, in extreme cases, cancer. Your doctor may perform genetic testing to better understand your condition.
Neurological examination
A neurological examination assesses sensory and motor functions, and can generally be done in your GPs office. The doctor may check your vision, hearing, balance, coordination, strength, and reflexes, depending on the signs and symptoms you have described. Any problem that is detected in this exam can help determine which portion of the CNS needs further investigation.
Endocrine studies & blood tests
Endocrine studies involve blood and/or urine tests and imaging tests (see below) to analyse your hormone levels and detect any abnormalities. Some of these tests may include:
- General blood test to assess overall health.
- Blood catecholamine studies, which measure levels of certain catecholamine levels in your blood.
- 24-hour urine test, which measures levels of catecholamine levels in your urine.
Imaging tests
The doctor will take images of your body using magnetic resonance imaging (MRI), a computed tomography scan (CT scan), ultrasounds, and/or positron emission tomography (PET scan), depending on where it is suspected the cancer is. The doctor may also look at other parts of the body and look for signs of metastasis. Your doctor may also recommend a somatostatin receptor scintigraphy scan, which involves injecting a radioactive substance into the bloodstream which attaches to the tumour and shows where the tumour(s) are located in the body.
Biopsy
Once the location of the cancer has been identified, the doctor will perform a biopsy to remove a section of tissue using a needle. This tissue will then be sent to the lab and analysed for cancer cells.
Prognosis (Certain factors affect the prognosis and treatment options)
While it is not possible to predict the exact course of the disease, your doctor may be able to give you a general idea based on the extent of the disease, susceptibility to treatment, age, overall fitness, and medical history. It is very important to discuss your individual circumstances with your doctor to better understand your prognosis.
References
Some references are to overseas websites. There may be references to drugs and clinical trials that are not available here in Australia.