Von Hippel-Lindau disease (VHL): symptoms, screening and care in the UK

Von Hippel-Lindau disease is a rare inherited condition in which a fault in one gene predisposes a person to growths in several organs. Guy’s and St Thomas’ NHS Foundation Trust describes it as an inherited condition that causes an increased risk of developing malignant (cancer) and benign (non-cancer) tumours and cysts. It is often shortened to VHL, and clinicians may also refer to VHL syndrome.

The gene involved is called VHL. Genes are coded messages that give instructions for how cells in the body grow and function, and the trust explains that the job of the VHL gene is to protect us by controlling the growth of cells. When one copy carries a harmful change, the protective effect is reduced and the risk of tumours and cysts rises.

The word syndrome is used because the problem is not a single lump in one place. VHL is better thought of as a lifelong tendency to develop a pattern of related growths that need coordinated monitoring, which is why care is led by a specialist genetics service and a multidisciplinary team rather than by one organ specialist.

According to the trust, the tumours can affect different parts of the body. The list it gives is:

• the back of the eye (retina)

• the kidneys

• the back of the brain (cerebellum)

• the spinal cord

• the adrenal gland

• the inner ear (endolymphatic sac)

• the pancreas

The NHS pages on related conditions help explain why particular organs are checked. The NHS describes a phaeochromocytoma as a rare tumour of the adrenal glands that can cause the glands to produce too much of the hormones that control heart rate, blood pressure and metabolism, often resulting in problems such as heart palpitations and high blood pressure. It says that up to 1 in every 3 occurs as part of an inherited genetic disorder, such as von Hippel-Lindau syndrome or neurofibromatosis type 1, and that a doctor may recommend genetic testing to see if you have one of these disorders.

The NHS says symptoms of a phaeochromocytoma tend to be unpredictable, often occurring in sudden attacks, and can include headaches, heavy sweating, palpitations, high blood pressure, a pale face, feeling or being sick, feeling anxious or panicky, and shakiness. Some people have no symptoms at all, which is one reason regular hormone testing forms part of VHL screening.

For the kidneys, the NHS notes that you may be more likely to get kidney cancer if you have certain inherited genetic conditions, and Cancer Research UK lists von Hippel-Lindau disease among the inherited conditions that increase the risk of kidney cancer. The NHS stresses that any symptoms of kidney cancer should be checked by a GP.

Not every growth is dangerous. Many are benign cysts or slow-growing lesions, but because they sit in sensitive places such as the eye, brain or spinal cord, early detection allows treatment before they cause harm. Your specialist team explains which findings need watching and which need treatment.

The trust explains that genes come in pairs and we inherit one copy from each parent. Someone with a VHL mutation also has one normal copy, and only one copy of each gene pair is passed on to a child. A person with a mutation in one copy therefore has a 1 in 2 (50%) chance of passing it to each child.

Predictive testing is offered where genetic testing has already been carried out in the family and has confirmed a mutation in a VHL syndrome gene. It involves a blood sample to check whether you have inherited the same mutation. The trust says it discusses what the test could mean before it is offered, and that results take 4 to 6 weeks once the blood sample and all necessary information have been received.

There are two possible answers. If you have not inherited the family mutation, your own risk of VHL-related tumours and cysts is not higher than anyone in the general population, and you cannot pass the mutation on to your children. If you have inherited it, you have an increased chance of developing the tumours and cysts, though not a certainty.

Choosing to be tested is a personal decision. The trust invites people to think about timing, the psychological impact of knowing, how they would share the result within the family, the possible effect on employment or insurance, and their own coping strategies. Not everyone chooses testing, and the trust says that those who decline may still be eligible for regular screening.

People with a diagnosis are cared for by a multidisciplinary team, which the trust says includes a range of specialist health professionals such as doctors, nurses, physiotherapists and pharmacists. They are eligible for regular screening to look for VHL-related tumours. The schedule published by the trust is:

There is no single treatment for VHL because treatment depends on which growths are present and how they behave. Many are monitored and treated only when they reach a size or position that threatens function. For a phaeochromocytoma, the NHS says most people will need surgery to have it removed, with alpha blockers (and sometimes beta blockers) given for several weeks beforehand to stabilise heart rate and blood pressure, and that most tumours can be successfully removed by surgery.

Outlook varies a great deal, including between members of the same family. The trust notes that different members of the same family can be affected differently, and that most people with VHL syndrome will develop one of these tumours. Regular surveillance is intended to find problems at an early stage, when they are usually easier to treat.

Support is available beyond the clinical team. The trust names clinical psychologists, your GP and the charity VHL UK Ireland among the sources of support, and it recognises that receiving results can be a challenging time.

The trust recommends being vigilant about your body and letting your GP know if you are concerned about any symptoms of VHL-related tumours and cysts. Persistent headaches, unsteadiness, changes in vision, numbness or weakness, or episodes of sweating, palpitations and anxiety should be mentioned to your GP or genetics team rather than put down to something else, especially if there is VHL in the family.

Sudden severe symptoms, such as sudden loss of vision, a severe sudden headache or weakness on one side of the body, need emergency care via 999 or A&E. If you have a family history but no diagnosis, ask your GP about referral to a clinical genetics service.