Every day with Neurofibromatitis raises a new question

What is neurofibromatosis?

Neurofibromatosis is a name traditionally used for a group of genetic conditions that cause tumors to grow on or around nerves. These conditions can affect different parts of the body, and their symptoms and impact vary from person to person.

‍

Today, this group is often referred to collectively as NF, covering neurofibromatosis type 1 and the different types of schwannomatosis.

What are the different types?

The conditions grouped under NF include:

‍

• Neurofibromatosis type 1 (NF1): The most common type. It can cause light-brown skin patches, freckles in the armpits or groin, and tumors called neurofibromas. It may also affect learning, vision and bones.
• NF2-related schwannomatosis: Previously called neurofibromatosis type 2. It often involves tumors on the nerves responsible for hearing and balance.
• Other types of schwannomatosis: These include SMARCB1-related and LZTR1-related schwannomatosis. They cause tumors called schwannomas to grow on nerves and can cause pain and other nerve-related symptoms.

These are distinct genetic conditions. One type does not turn into another.

‍

What is neurofibromatosis type 1 (NF1)?

Neurofibromatosis type 1, or NF1, is a lifelong genetic condition that can affect the skin, nerves, eyes, bones and other parts of the body. It is caused by a change in the NF1 gene, which normally helps control cell growth.

‍

NF1 affects each person differently. Some people have mainly skin changes, while others develop tumors along nerves, pain, vision problems, bone changes or learning difficulties. Most tumors associated with NF1 are noncancerous, but they can still cause symptoms depending on their size and location.

‍

What Causes NF1?

NF1 is caused by a disease-causing change in the NF1 gene. This gene provides instructions for producing neurofibromin, a protein that helps prevent cells from growing and dividing too quickly. When neurofibromin does not work normally, tumors called neurofibromas can develop along nerves.

‍

A person is born with NF1; it is not caused by lifestyle, diet, stress or anything a parent did during pregnancy. In around half of people, the gene change is inherited from a parent with NF1. In the other half, it occurs for the first time in that person.

‍

Living With NF1

NF1 can affect appearance, comfort, mobility, education, work, relationships and confidence. Because many effects are not visible, other people may not always understand the impact of pain, tiredness, uncertainty or repeated medical appointments.

‍

Keeping a record of new lumps, changes in existing tumors, pain, headaches, vision changes and daily limitations can help make appointments more productive. Photographs may also help track visible changes over time, although they should not replace a medical examination.

‍

Forms of NF1

Most people have generalized NF1, meaning the NF1 gene change is present throughout the body. Features may develop in several areas and can change as the person grows older.

‍

Some people have mosaic NF1, previously called segmental NF1. In mosaic NF1, the genetic change occurred after conception and is present in only some of the body’s cells. Features may therefore be limited to one area or one side of the body, although the pattern can vary.

‍

NF1 is different from NF2-related schwannomatosis and other forms of schwannomatosis. Although these conditions were historically grouped together, they are caused by different gene changes and tend to produce different types of tumors and symptoms.

‍

How Is NF1 Monitored?

Monitoring is personalized according to age and symptoms. It may include skin and neurological examinations, blood-pressure measurements, eye checks, assessment of growth and bones, and discussions about pain, learning, development and emotional well-being.

‍

Scans are generally used when symptoms or examination findings suggest a deeper tumor or another complication. Routine brain or whole-body imaging is not automatically required for every person with NF1, and the benefits and limitations should be discussed with the specialist team.

‍

How Is NF1 Treated?

There is currently no single treatment that removes the underlying genetic condition. Care focuses on monitoring NF1, managing symptoms and treating individual complications when necessary.

‍

Cutaneous neurofibromas may be removed when they cause pain, irritation or significant distress. Surgery may also be considered for some plexiform neurofibromas, although complete removal can be difficult if the tumor surrounds important nerves or structures. Pain, bone problems, vision changes and learning difficulties may each require support from different specialists.

‍

Targeted Treatment for Plexiform Neurofibromas

Medicines called MEK inhibitors may be considered for certain symptomatic plexiform neurofibromas that cannot be safely or completely removed with surgery. These treatments act on a cell-signaling pathway affected by the NF1 gene change and may reduce tumor size or related symptoms in some people.

‍

MEK inhibitors do not cure NF1 and are not appropriate for every neurofibroma. They require specialist supervision and regular monitoring for possible side effects. The treatments available and the circumstances in which they are used may differ between healthcare systems.

‍

Who is at risk of developing NF1?

The main risk factor for NF1 is having a disease-causing change in the NF1 gene. A person with NF1 has a 50% chance of passing the gene change to each child, regardless of the child’s sex.

‍

Someone can also develop NF1 without any family history because a new gene change can occur. The condition is not linked to lifestyle choices, and there is currently no established way to prevent it.

‍

Most neurofibromas are noncancerous. However, people with NF1 have an increased risk of certain tumors, including malignant peripheral nerve sheath tumors, which can develop from a nerve-related tumor. Warning signs may include rapid growth, new persistent pain, pain that wakes a person at night, a change from soft to hard or new weakness or numbness.

‍

Other possible complications include vision loss from an optic pathway glioma, spinal or bone problems, seizures, blood-vessel abnormalities, high blood pressure and hormone-related conditions. Some people also have a higher risk of particular cancers, but the individual level of risk varies.

‍

What are the symptoms of NF1?

NF1 affects each person differently, and symptoms may appear or change over time. Common features include café-au-lait spots, freckling in the armpits or groin, and neurofibromas on or under the skin, which may cause itching, tenderness or discomfort.

‍

Plexiform neurofibromas grow along nerves and can sometimes cause pain, swelling, numbness, weakness or problems with movement, vision, breathing or swallowing. NF1 may also affect the eyes, bones and nervous system, leading to vision changes, scoliosis, headaches, seizures, high blood pressure or chronic pain.

‍

Learning, attention and coordination difficulties are also common and may affect reading, memory, concentration or planning.

‍

Rapid tumor growth, persistent pain, new weakness, numbness or vision changes should be discussed promptly with the healthcare team.

‍

How is NF1 diagnosed?

NF1 is often diagnosed using a combination of physical features, medical history and family history. Diagnostic features can include multiple café-au-lait macules, freckling in the armpits or groin, neurofibromas, a plexiform neurofibroma, characteristic eye findings, certain bone changes or a parent with NF1.

‍

Genetic testing can identify a disease-causing change in the NF1 gene and may be helpful when the diagnosis is uncertain, when a young child has not yet developed enough features or when family planning is being considered. A negative test does not always completely rule out NF1, so results should be interpreted by an appropriate specialist.

‍