Neurofibromatosis Type 1 Skin and Brain

Neurofibromatosis Type 1 (NF1) is a genetic condition that affects approximately 1 in 3,000 people. In the Netherlands, around 4,000 to 6,000 people have NF1. The symptoms of NF1 can manifest in various ways, even within the same family. Many people with NF1 do not feel ill. Symptoms can range from mild skin issues to learning, emotional, and behavioral problems. While NF1 cannot be cured, symptoms can be treated.

The diagnosis of NF1 can be confirmed through DNA testing, where a mutation in the NF1 gene is sought in the blood. This test is done for several reasons. First, to confirm that it is indeed NF1. If no mutation is found in the blood, it may indicate a different syndrome, such as Legius, Noonan, or LEOPARD syndrome. Second, to determine the type of mutation, as some mutations may cause the condition to be more severe or milder than others. Third, for family testing, to check whether family members also carry the NF1 mutation. Additionally, DNA testing is used for prenatal diagnosis during pregnancy via chorionic villus sampling. It is also used for pre-implantation genetic diagnosis (PGD) during in vitro fertilization to determine whether the embryo has NF1.

NF1 is a genetic condition caused by a change in the NF1 gene. This condition is dominantly inherited, meaning that a child has a 50% chance of inheriting NF1 from an affected parent. Half of the people with NF1 inherit it from a parent, while the other half acquire it through a new mutation.

For parents of a child with a new mutation, the chance of having another child with NF1 is low. However, there is a small chance of a specific genetic situation called germline mosaicism, where the risk for NF1 in the next child is again 50%. Sometimes, the mutation is present only in a part of the parent's body. It is important to seek advice from a clinical geneticist well before pregnancy.

• Café-au-lait spots: Light brown pigment spots on the skin.
• Freckles: Especially in the armpits and groin area.
• Neurofibromas: Benign lumps on, in, or under the skin.
• Lisch nodules: Pigment accumulations in the iris.
• Tumors on the optic nerve: These can cause vision problems.

• Learning, emotional, and behavioral problems: Many children with NF1 experience learning difficulties and may require additional support at school.
• Developmental delays: Children often develop more slowly than their peers, for example, in learning to walk, talk, and ride a bike.
• Intellectual disability: Around 4-8% of children with NF1 have an intellectual disability.
• Headaches and epilepsy: These are more common in people with NF1.
• Sleep problems: Issues with falling asleep and staying asleep.