Fifth Anniversary Issue - What We Have Learned

Five years ago when three families got together to form the VHL Family Alliance, our greatest concern was to assemble knowledgeable medical information about what was then quite a mysterious, little known condition.

In June of 1993 the gene was found, beginning a new era of DNA diagnosis. In addition to being able to diagnose VHL through a collection of signs and symptoms, the possibility now existed to identify people with no clear set of clinical affects. By 1998, this technology is fairly well established in a few well-equipped centers, and is available to physicians and families worldwide.

Major studies on VHL have been conducted over the last 5-10 years at the University of Freiburg, Germany; the U.S. National Institutes of Health; and the French VHL Study Project in Paris.

What we knew as of 1993 was that everyone with clinically diagnosed VHL has a change in the VHL gene. What we do not know is: what percentage of people with a change in the VHL gene ever develop clinical symptoms of VHL? Have we perhaps been looking at the tip of the iceberg -- only recognizing the people with clinically significant symptoms?

We often see wide variations among siblings in the same family, with the same copy of the VHL gene -- one sibling with a very light case, another sibling with a very severe case. Now we are finding an increasing number of adults in their 50’s and older who have the VHL mutation, but few if any clinical affects. In the last year we have seen two sisters diagnosed in their 80’s, one 76-year-old, one 60, one 49 -- all with no presenting clinical symptoms. These diagnoses were all made through DNA diagnosis, usually to understand the source of VHL in a child or grandchild.

We are realizing now that VHL is a genetic risk factor, like the genes for breast and colon cancer. It is a predisposition factor. It does not automatically create a certain set of effects. It is clear that there are some "modifier effects" among our other genes and in diet and environment which we do not yet understand.

It's as though you have been given ten tickets for the lottery. You don't know if you're going to win anything or not. But you shouldn't simply throw them away -- you should watch for results just to make sure. Knowing that you have a change in the VHL gene is an early warning sign which you can use to your advantage to take protective action so that you never experience the worst effects of VHL.