Summary

The VHL gene test is requested along with other tests when a doctor suspects that someone has Von Hippel-Lindau syndrome. It may also be ordered to predict if a family member has an inherited mutation or variant in the VHL gene. VHL is the only gene known to be the cause of Von Hippel-Lindau syndrome.

Why get tested?

Von Hippel-Lindau syndrome is a rare inherited disorder. The features of the disease include an abnormal growth of blood vessels in certain parts of the body which form benign growths known as angiomas. These may develop in the brain, spinal cord, eyes, ear, adrenal glands, pancreas, kidney, and reproductive tract. The growths are usually benign, but some may be cancerous. People with Von Hippel-Lindau syndrome are at increased risk of developing cancers of the kidney and pancreas. Features of the condition may vary greatly between people, and even between those in the same family. The age of onset of symptoms may also vary, although tumours usually first appear in young adulthood. 

Inheritance
Von Hippel Lindau syndrome results from a mutation in a gene known as the VHL gene.  Genes come in pairs and a child inherits one gene from each parent. Although many genetic disorders require faulty genes to be inherited from both parents, this is not the case with the VHL gene. Since the VHL gene is a dominant gene, it only takes one faulty copy, inherited from either a mother or father, to cause Von Hippel Lindau syndrome. This means that if one parent has a mutation on the VHL gene their children have a 50 per cent chance of inheriting the mutation. 

What the VHL gene does

The VHL gene provides instructions for making a protein that functions as part of a group of proteins that work together. This protein made by the VHL gene is classified as a tumour suppressor, which means it prevents cells from growing and dividing too rapidly or in an uncontrolled way.

The group of proteins is the VCB-CUL2 complex, and they target other proteins to be broken down when they are no longer needed. One of the targets is a protein called hypoxia-inducible factor 2-alpha. HIF controls several genes that are involved in cell division, the formation of new blood vessels, and the production of red blood cells.

More than 370 inherited mutations in the VHL gene have been identified in people with Von Hippel-Lindau syndrome. The mutations either prevent the production of any VHL protein or lead to the production of an abnormal version of the protein.

Having the test

Sample 
Blood 

Any preparation?
None

Your results

Having a VHL gene mutation increases your risk of developing tumours in certain parts of the body including the eyes, ears, brain, spinal cord, adrenal glands, pancreas, kidneys and reproductive tract. Not everyone with Von Hippel-Lindau disease will develop cancer over their lifetime.

The genetic testing methods we have available at the present time can detect more than 80 per cent of all VHL mutations. Once a mutation has been identified in one family member, genetic testing for VHL in other family members is 100 per cent accurate. It is important to have genetic counselling before undergoing genetic testing.  

Family members at risk of developing Von Hippel-Lindau syndrome are offered surveillance and early intervention to reduce the risk or severity of the disorder.

Relatives of those with Von Hippel-Lindau syndrome can also be tested for the same mutation to determine whether they would benefit from regular screening. If a relative is found not to have inherited the mutation, then no further screening is necessary. If a person does not have the faulty VHL gene, they have the same chance of developing cancer as the general population, unless there are other factors that increase this risk.

The test is covered by Medicare when ordered by a specialist doctor.