Because Neurofibromatosis Type II (NF2) is an autosomal dominant condition, the siblings and children of a person with NF2 have as much as a 50% chance of also having NF2. However, this is not always the case. About half of the time, a person with NF2 is the first person in their family to have a mutation. This is called a de novo, or new mutation. When this happens, any future children of the person diagnosed will have a 50% chance of inheriting the NF2 mutation, but the parents and siblings would not be at risk.
Another scenario that can change who in the family might need testing is called mosaicism. When people are born with a genetic mutation, that mutation is typically present in every cell of their body. Of those with a de novo NF2 mutation, between 25-30% have a mutation that is mosaic, meaning the mutation is not present in every cell of their body, only some cells. Mosaicism can make testing difficult because it can be impossible to know which cells in the body might have the mutation and which cells do not. For example, most often, genetic testing is done on blood cells called leukocytes. But, if the DNA in the leukocytes does not show a mutation in the NF2 gene, it could be because that mutation is present in other cells, like nervous system cells, and is still causing the features of NF2 in those cells. In these cases, when a person’s symptoms or features are still very suspicious for NF2, but the blood DNA testing does not find a mutation, it is possible to test a person’s tumor for NF2 mutations. It can also be a challenge to figure out what the risks are for the children of a person with a mosaic form of NF2, which can also be called segmental NF2. This is because the egg or sperm cells of the parent, may not carry the mutation. Because a negative blood DNA test can be misleading, it is very important for anyone who has features of NF2 to meet with a physician or genetic counselor who has expertise in this condition and can properly explain these types of test results so nothing is missed.
A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website. Genetic counselors can be found on the National Society of Genetic Counselors website.
