Epilepsie onderzoek meisje 2022 32

The genetic condition Neurofibromatosis Type 1

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. 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. NF1 is not curable, but symptoms can be treated.

Diagnosis

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

Inheritance and desire for children

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 of 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.

Characteristics of NF1

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

Neurological symptoms

  • Learning, emotional, and behavioral problems: Many children with NF1 have 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.

Skeletal abnormalities

In some people with NF1, there is abnormal bone development. This is often noticeable at birth, usually in the skull or limbs. Sometimes, newborns may have a curvature of the lower leg or forearm, which can lead to a pseudo-joint and loss of function. This can be treated with a brace or surgery. There may also be sphenoid dysplasia, where part of the bone at the back of the eye socket is missing, causing facial asymmetry and potential eye problems.

Approximately 1 in 10 people with NF1 have scoliosis, a sideways curvature of the spine, which can worsen during puberty. Additionally, people with NF1 are often shorter than their family members and may have a larger head circumference, which typically has no medical significance. They also often have lower bone density, which can be improved with vitamin D, especially in children under four years old and adults during months with an ‘R’.

Endocrine symptoms

  • Early or late puberty: This is more common in children with NF1 and may require hormonal treatment.
  • Growth hormone deficiency: Treatment with growth hormone may be necessary.

Malignancies (cancer)

People with NF1 have an increased risk of certain types of cancer, particularly malignant tumors in deep (plexiform) neurofibromas, also known as MPNST. About 1 in 10 people with NF1 develop this form of cancer. Warning signs include severe, increasing pain and neurological deficits such as difficulty walking, reduced strength in an arm or leg, or reduced sensation in the skin.

A certain type of leukemia is also more common in children with NF1. Regular physical examinations by a doctor are important. Additionally, breast cancer appears to occur earlier in women with NF1. Therefore, women between 35 and 50 years are advised to have an annual mammogram via their general practitioner.

Psychological and social aspects

People with NF1 can experience not only physical symptoms but also psychosocial problems. It is important to discuss these issues with healthcare providers. Families with NF1 often need support for behavioral issues and school choice. Parents can be doubly burdened if they also have NF1. Social interactions can sometimes be difficult, leading to isolation and loneliness. Contact with others in similar situations can be helpful.

Many people with NF1 are concerned about their appearance and may receive unwanted attention, which can lead to avoidance behavior. Adolescents often experience psychosocial problems and may benefit from psychological support and contact with peers who also have NF1. They may struggle with finding work, living independently, and forming friendships. Loneliness is common. It is important to discuss these issues with the general practitioner or specialized NF1 physician. NF1 should not be a barrier to obtaining a driver's license, but it may require additional medical evaluations.

Medical care for NF1

The care network for NF1 consists of specialized care provided by experienced doctors and professionals. People with NF1 should be regularly monitored by a lead NF1 physician, who works closely with treatment and expertise centers. Check-ups follow a set schedule and focus on all aspects of NF1, including development and socio-emotional health. It is important to eat healthily, exercise regularly, and take vitamin D during the winter months. Annual blood pressure checks are recommended, and for women between 35 and 50 years old, an annual mammogram through the general practitioner should be scheduled. Membership in the NF association (NFVN) can provide additional support and information.