Neurofibromatosis is a genetic disease caused by a mutation, i.e. a change in the genetic material. The affected gene encodes for neurofibromin, which is a protein important for suppressing tumors. In other words, it counteracts the development of tumors. For this reason, the risk of cancer goes up when neurofibromin is lacking.
With around 1 in 3000 people affected, NF1 is the most common type of neurofibromatosis. Around half of the cases are passed down by parents to their children; heredity is therefore autosomal dominant. Penetrance is nearly complete; in other words, the disease always manifests with clinical symptoms, though without a good genotype-phenotype correlation. This means that the symptoms of the disease may be very different even within a family that has the same mutation. It is therefore impossible to predict the severity of the disease. The other half of the cases are due to a spontaneous or new mutation, called a de novo mutation.
In addition, there is also segmental NF1, where the disease is restricted to just a certain part of the body, such as a leg. This is also called a mosaic form of NF1. In such cases, the mutation does not affect all of the cells in the body, but only some. This means that healthy and affected cells are found side-by-side.
A genetic examination is generally possible and is recommended to confirm the diagnosis, especially in children, in whom the disease is only apparent through the characteristic skin changes. The mutation can be found with a clinically confirmed diagnosis in 95% of those affected. If this is not the case, it is recommended to conduct further genetic diagnostics to check for the presence of a disease similar to NF1.