The Von Hippel-Lindau syndrome is caused by mutations – or genetic changes – in the VHL gene. This gene encodes for the VHL protein, which normally binds the HIF protein and breaks it down, thereby blocking the release of growth factors (mainly for vessels).
Now if the VHL gene is altered, the VHL protein will not be produced correctly and will then be unable to bind to the HIF protein and break it down. This will cause the HIF protein to accumulate, thereby leading to an increased release of growth factors (mainly for vessels), which promotes tumor growth and enhances the blood supply to the tumors.
Most of the people affected inherited the genetic change from a parent. Around 80% of patients have a parent who also suffers from Von Hippel-Lindau syndrome. Heredity is autosomal dominant. The remaining cases (20%) are due to a spontaneous or new mutation, called a de novo mutation.