Genetics

The three forms of neurofibromatosis (NF) are genetic conditions. Although they are distinctly different conditions, NF1 and NF2 are both inherited in what is called an autosomal dominant manner. The genetics of Schwannomatosis is more complex, but families in which the condition is inherited have shown an autosomal dominant pattern of inheritance as well.

Around half of people diagnosed with NF1 or NF2 will have inherited the condition from one of their parents. The other half are the first in their family to have the condition. When this occurs it is considered to be the result of a new or spontaneous change in the spelling of the gene. This is sometimes referred to as a sporadic mutation.

Each time a person with NF1, NF2 or Schwannomatosis has a child, that child has a 1 in 2 (or 50%) chance of inheriting the condition.

This picture shows autosomal dominant inheritance through an example of how these conditions are inherited. We all have two copies of most genes, and each gene is an instruction to the body, a bit like a recBBipe. In genetic conditions with autosomal dominant inheritance, like NF, one copy of a particular gene has a spelling mistake. This means that the intended instruction does not get through, so the recipe is not quite right. In the picture below, the copy of the NF gene with the spelling mistake is shown as NF, while the copy of the gene that functions normally is shown as nf. So, a person who has the combination NFnf would have the condition and is represented in black, and a person with the combination nfnf would not have the condition and is represented in grey. Every time a person has a child they will pass on only one of their two copies of the gene so that the child has one copy from mum and one copy from dad.

Parents with a child affected by NF1, NF2 or Schwannomatosis but who do not have the condition themselves have a much lower chance of having another affected child (much less than 50%). Their chance is much less, in fact, almost the same as that of any couple in the general population.

Schwannomatosis is most commonly (in 85% of affected people) caused by a spontaneous gene change. However, because it is a very rare condition, more is still to be determined about the genetics of this condition.

Some people only have features of NF1, NF2 or Schwannomatosis on only one part of their body, although this is much less common. These people may be diagnosed with segmental or mosaic NF1, NF2 or Schwannomatosis. For people with this diagnosis the chance of passing on the condition to their children may be as low as it is for the general population, but this depends on which part of the body is affected. If the affected area includes the ovaries or testes, then the chance could be as high as 50%.

Genetic Counselling

Genetic counselling can help families affected by NF to talk about and understand; a new diagnosis, the decision-making process in regards to starting a family, having another child, genetic testing and health management for those who have the condition.

One aim of genetic counselling is to provide couples and individuals with the information they need to make an informed decision about an aspect of their condition through provision of information, issue clarification, and the presentation of alternative options. Genetic counsellors will not make the decision for you, or tell you what decision to make, instead they will help you to make a decision which is right for you.

Genetic counsellors often work closely with clinical geneticists (genetic doctors), and are linked in with numerous other specialists. A genetic counsellor may be available at your diagnostic or ongoing management appointments. They are a great point of contact if you have concerns or questions.

Click here for a list of genetics services around Australia and speak with your GP or specialist if you are interested in a referral to a genetic clinic.

Genetic Testing

While the diagnosis of NF1 and NF2 is usually based on clinical findings, there are now genetic tests available for people affected by or with a family history of NF. Clinical diagnosis remains the standard for diagnosis due to there being few clear links between the type of spelling mistake in the gene a person has and the symptoms or features of NF that they will present with. That is, there is no known clinical benefit to doing the genetic test. For this reason, genetic testing is mainly used for families who want to pursue pre-implantation genetic diagnosis (PGD) or prenatal diagnosis. As the technology becomes more accessible, choices for genetic screening will expand. Options should be discussed with a clinical geneticist or genetic counsellor. Policies surrounding the provision and funding of genetic testing can vary between genetics services.

Genetic testing can be useful if an affected parent wishes to use that information for prenatal diagnosis. Chorionic villous sampling, or amniocentesis, can sometimes determine if a woman’s unborn child has the condition. This would only be performed if the parents wish to discontinue the pregnancy should the test reflect a positive diagnosis of NF1 or NF2. In the case of NF1, the gene test does not provide information concerning further possible complications of NF in the individual. These tests would be offered once the specific spelling mistake in the gene is identified within the family.

Another option for couples affected by NF1 or NF2 looking to have a family is Pre-implantation Genetic Diagnosis (PGD). While this is a costly procedure, it can be used to ensure that a couple has children who are not affected by NF1 or NF2. This procedure involves the use of assisted reproductive technology such as in-vitro fertilisation (IVF) to produce embryos which are then genetically tested for the known mutation in the family, and then only healthy embryos are transferred into the woman’s uterus and allowed to develop normally.

Further information about the genetics of NF and genetic testing can be found on the NSW Health Centre for Genetics Information website.