Von Hippel-Lindau (VHL) syndrome: VHL gene, tumour risk and surveillance

VHL syndrome is an inherited tendency to develop both cancerous and non-cancerous tumours and cysts. Guy's and St Thomas' lists the places they can arise: the back of the eye (retina), kidneys, the back of the brain (cerebellum), spinal cord, adrenal gland, inner ear (endolymphatic sac) and pancreas. Cancer Research UK describes abnormal collections of blood vessels in the brain, spine and back of the eye, and says most tumours are benign, though some people have an increased risk of pancreatic neuroendocrine tumours and kidney cancer.

There is no single typical story. The Trust says most people with VHL syndrome will develop one of these tumours, and different members of the same family can be affected differently. Having the gene change does not mean a person will definitely develop any particular tumour or cyst, though most will have some symptoms by the age of 65.

Genes come in pairs, one copy from each parent. The VHL gene normally protects the body by controlling the growth of cells. A person with VHL syndrome has a mutation in one copy and a normal second copy, and the Trust explains that a mutation in one copy is enough to cause an increased risk of VHL-related tumours and cysts.

Cancer Research UK includes VHL among the inherited cancer conditions and gives it as a rare condition caused by a change in the von Hippel-Lindau gene. It sits alongside conditions such as Birt-Hogg-Dube syndrome and tuberous sclerosis in its list of inherited syndromes that can involve kidney tumours.

VHL is autosomal dominant. Only one copy of each gene pair is passed to a child. If a person has a mutation in one copy, the Trust says there is a 1 in 2 (50%) chance of passing on that mutation to each child, regardless of the parent's gender or the child's gender.

The usual route into testing is through a family. The Trust describes predictive testing as being for people where genetic testing has already shown a VHL mutation in the family. A blood sample can show whether a relative inherited the same mutation. Because every first-degree relative has a 1 in 2 chance, finding a mutation in one person gives the family a way to know who needs surveillance and who does not.

The Trust stresses that deciding to be tested is personal, can be difficult and complex, and that not everyone chooses it. If someone decides against testing they may still be eligible for regular screening, and the team will discuss this. It lists questions worth thinking through: the timing and whether the result will change immediate treatment, how it might feel to find a mutation, how to share the information in the family, the effect on children and relationships, and employment or insurance.

Cancer Research UK, for inherited cancer conditions in general, says a genetic counsellor helps people think through advantages and disadvantages, and that children under 18 cannot usually be tested for cancer risk genes. Predictive gene tests in VHL take 4 to 6 weeks once the blood sample has been received and all the information needed is available, according to the Trust, and results are followed by further appointments if appropriate.

People with VHL syndrome are cared for by a multidisciplinary team and are eligible for regular screening for VHL-related tumours. The Trust sets out the schedule it follows.

• From infancy and early childhood: an annual eye examination.

• From 8 years of age: annual blood or urine tests for hormones called metanephrines, which check for adrenal tumours.

• From adolescence: MRI scans of the head every 12 to 36 months.

• From 14 to 16 years of age: annual abdominal scans, annual hearing tests and an annual neurological assessment by a neurologist.

• At all ages: awareness of symptoms. The Trust asks people to tell their GP about any symptom that might be due to a VHL-related tumour or cyst.

The Trust says support is available from a clinical psychologist, the GP and the VHL UK Ireland Charity, and that its genetics clinician will go through the options. Regardless of the result of testing there may be an opportunity to take part in research, which a genetics clinician or research nurse can discuss.