The genes involved in NF are important in controlling and stopping cell growth and division. If there is a gene mutation that causes the gene not to function correctly, cells continue to divide and a tumor forms. Therefore the genes are referred to as tumor suppressor genes because in their normal form they stop uncontrolled cell division.
NF1/NF2: Approximately half of individuals with NF1 or NF2 inherit the condition from one of their parents. The other half develop it as the result of a spontaneous (also called new or de novo) change in one of the NF genes in the egg cell or sperm cell during conception. Both NF1 and NF2 follow autosomal dominant inheritance. This means that individuals with either of these conditions have a 50% chance of passing the condition on to their offspring. If a child inherits the NF gene, they will always show symptoms of the condition, however, it is difficult to predict the severity, especially in NF1. This is called variable expressivity. If a child of someone with NF does not inherit the NF gene, they do not have NF and therefore cannot pass it on to their future children. That is to say, NF cannot “skip a generation.”
Schwannomatosis: The inheritance of schwannomatosis is less well understood and appears to involve more than one gene. Regardless, the majority of cases of schwannomatosis appear to occur by chance and are not inherited. However, once an individual has schwannomatosis, it may be inherited as an autosomal dominant condition and therefore, the chance of someone with schwannomatosis having a child with the condition may be 50%. Contrary to NF1 and NF2, not all individuals in a family with schwannomatosis will develop tumors or show signs of having the condition. This is called reduced penetrance.
Segmental NF and mosaic NF are similar in that there is a mixture of cells with and without the NF gene change. It is thought that this is the result of a genetic change that occurred after conception leading to a combination of normal and abnormal cells. Individuals with segmental or mosaic types of conditions are at risk of having children with the genetic change in all of their cells and therefore may be more severely affected than the parent.
In segmental NF, the area that is involved is typically confined to a specific area of the body such as an arm, half of the body or along the spine.
Contrary to segmental NF, in mosaic NF the affected area may not be confined to a specific area and may appear as a milder case of the condition or may affect various areas throughout the body.
For more information, please contact a genetic counselor or talk with your NF provider.