Do you have strange spots or lumps on your body? Let's talk about Neurofibromatosis (NF)!

Do you have those coffee-colored spots on your skin that you've probably seen since you were a child? Or do you sometimes have small, lumpy things that appear in places on your body? Maybe these aren't just spots or lumps. Today we're going to talk about a condition that can be like that, and it's a bit complicated but understandable. That's Neurofibromatosis , or NF for short.

What is Neurofibromatosis (NF)?

Simply put, Neurofibromatosis (NF) is a group of conditions that affect our nervous system and genes . It affects our brain, spinal cord, nerves, and skin. The symptoms you experience can vary from person to person, and they also vary depending on the type of NF you have. But the most common symptoms are birthmarks and tumors that are usually non-cancerous (benign). You can also inherit the condition from your family, which is your genes. But surprisingly, in about 50% of cases, it can occur randomly, without any family history.

What are the main types of Neurofibromatosis (NF)?

There are three main types of these NFs. Let's see what they are.

1. Neurofibromatosis type 1 (NF1)

This is the most common type of NF. It occurs when:

• Café au lait spots: These look like coffee-colored spots. They can appear anywhere on the body.
• Neurofibromas: Small tumors that form on nerves.
• Freckles on the armpits and groin: They look like small dots.
• Optic nerve tumors: These can develop in the nerves that connect to the eye.
• Bone deformities: For example, things like scoliosis.

Imagine, there is a little girl named Nimali. When she was born, she had several milky coffee-colored spots on her body. As she grew a little older, small spots also appeared on her armpits. It was only when she showed them to a doctor that she learned that she had NF1.

2. NF2-associated Schwannomatosis (formerly called Neurofibromatosis type 2 (NF2))

This type happens:

• Slow-growing neuromas: These also form along nerves.
• Hearing impairment: Hearing loss may occur.
• Vision changes: Things like cataracts can occur.
• Numbness or weakness: You may feel like your limbs are numb (peripheral neuropathy).

3. Schwannomatosis (SWN)

This is the rarest type . There are several subtypes of this, depending on the genetic mutation. Sometimes there may be no symptoms at all. But if symptoms do appear, here are some things that can happen:

• Slow-growing nerve tumors (Schwannomas): These can sometimes develop in only one part of the body.
• Chronic pain.
• Numbness and inflammation in the fingertips.

How common is Neurofibromatosis (NF)?

Roughly speaking, NF1 accounts for about 96% of all NF cases. That means that about one in 3,000 babies born each year worldwide has it. NF2 accounts for about 3%, that is, about one in 33,000 babies born. Schwannomatosis (SWN) is even less common, occurring in about 1%.

What are the symptoms of Neurofibromatosis (NF)?

As we mentioned earlier, symptoms vary depending on the type of NF. Some people may have no symptoms at all, while others may have severe symptoms. However, there are two main features that are common to all three types:

• Tumors: These are lumps of tissue that form when cells come together. Different types of NF tumors are made up of different types of cells. These tumors are often slow-growing and are not cancerous (benign) . However, very rarely, some tumors can become cancerous. These tumors that form on nerves are called Neurofibromas .

• Skin growths: These include birthmarks, such as the café au lait spots we discussed earlier, as well as moles that develop in the armpits and groin areas. Sometimes, small, soft, pea-sized lumps (cutaneous neurofibromas) can also develop on the skin surface.

The most important thing is not to be afraid that you have NF just because you have a couple of spots like this. However, if you have any doubts, it is best to seek medical advice.

In addition to these main symptoms, other symptoms may appear:

• Hearing or vision loss.
• Scoliosis.
• Muscle weakness.
• Numbness or tingling in the limbs.
• Body aches and headaches.
• Behavioral changes, such as Attention-Deficit/Hyperactivity Disorder (ADHD).
• Learning difficulties.
• Conditions like seizures.

What does someone with Neurofibromatosis (NF) look like?

This really varies from person to person. Some people may see small, round lumps (about a centimeter across, about the size of a pea) on their skin. These are neurofibromas. Some people may have more than two of these lumps, or they may have a large lump (plexiform neurofibroma) that is made up of several nerves under the skin.

We talked about café au lait spots. These can range in size and shape from flat, light brown to dark brown. You'll usually see six or more of these spots.

It's normal to have spots on our face. But in NF, these spots are most commonly seen in the armpits and groin areas . They look like small, reddish-brown dots.

At what age do symptoms of Neurofibromatosis (NF) appear?

This also varies from person to person. Some symptoms may be present at birth. Some may appear as you get older, in your teens, or as adults. For example, neurofibromas can be present on the skin of some babies at birth. But most often they appear in the teenage years. Café au lait spots are common in the first few years of a child's life. Freckles on the groin and armpits can appear between the ages of 3 and 5. Symptoms of schwannomatosis usually begin in adulthood, around the age of 30.

What causes Neurofibromatosis (NF)?

The main reason for this is a change (mutation) in our genes . Let's look at what causes each type:

• Neurofibromatosis type 1 (NF1): We have a gene called NF1 in our body. This controls the production of a protein called neurofibromin. The function of this protein is to suppress the formation of tumors.
• NF2-associated schwannomatosis/Neurofibromatosis type 2 (NF2): This is caused by a gene called NF2 (merlin) . This also controls another protein called neurofibromin. This protein also suppresses the formation of tumors.
• Schwannomatosis: This can be caused by mutations in the genes SMARCB1 or LZTR1 . However, in many cases, the exact gene that causes this condition cannot be identified.

Simply put, if there is a mutation in any of these four genes, the proteins don't receive the instructions needed to control the growth of our cells. That's when tumors start to form in the body.

You can inherit either NF1 or NF2 from your parents, which is called an autosomal dominant pattern . This means that you only need to get a copy of the altered gene from one of your parents to get the condition. However, about half of people with NF1 develop it spontaneously, without any family history. This can also happen to people with NF2. About 85% of people with schwannomatosis develop the condition spontaneously, without any family history.

What are the risk factors for Neurofibromatosis (NF)?

This condition can develop in anyone, but if someone in your family has one of these NF conditions, you are more likely to develop it too.

What are the possible complications of Neurofibromatosis (NF)?

NF can cause some complications. Some of them are:

• Hearing loss.
• Decreased vision.
• Persistent pain.
• Learning and behavior problems.
• Cardiovascular conditions - for example, hypertension, congenital heart conditions.
• Self-esteem issues due to skin conditions.
• A higher risk of developing cancer than the general population, including breast cancer and soft tissue cancer (sarcoma).

Important: Most NF tumors are not cancerous. However, very rarely, some NF tumors can become cancerous. Therefore, it is very important to have regular medical checkups.

How is Neurofibromatosis (NF) diagnosed?

A doctor will examine you and perform the necessary tests to diagnose NF. They will first examine your skin to check for signs of café au lait spots or neurofibromas. They will also check for scoliosis, blood pressure, vision, and hearing. They will also ask about your health and family medical history. So, if you know that someone in your family has NF, be sure to tell your doctor.

The criteria for diagnosing each type of NF are different. Although a clinical examination can often make the diagnosis, some tests can help determine the cause of your symptoms. Imaging tests, such as an MRI, X-ray, or CT scan, can show how the condition has affected your nervous system. Genetic testing can also help identify the gene mutation that is causing your symptoms. However, doctors have not yet identified all the genes that cause the condition.

Sometimes, symptoms are not diagnosed until years after they appear. Some people are diagnosed as adults. This is because NF symptoms develop over time, in stages.

What are the treatments for Neurofibromatosis (NF)?

This is very important: Your NF treatment should be under the guidance of a multidisciplinary team of doctors with expertise in NF patients . This team usually includes:

• Neuro-oncologists.
• Neurosurgeons.
• Ear, nose and throat surgeons (ENT surgeons).
• Plastic surgeons.
• Psychotherapists.
• Audiologists.
• Genetic counselors.

Although there is currently no cure for NF, there are many advances in the diagnosis and treatment of NF-related tumors. Your doctor will guide you to the best treatment for your condition.

If you have no symptoms, or your symptoms do not interfere with your daily life, you may not need any treatment. In that case, your doctor will ask you to come in for checkups once or twice a year to monitor the progress of the disease.

The doctor may recommend treatments such as:

• Tumor removal: Surgery can remove tumors on the skin and elsewhere in the body.
• Medications: The drug selumetinib has been approved by the US Food and Drug Administration (FDA) to stop the growth of tumor cells in children between the ages of 2 and 18 with NF1 who have plexiform neurofibroma tumors that cannot be removed by surgery, or whose tumors have caused disability or disfigurement.
• Surgery to correct bone growth abnormalities: If you have scoliosis or other bone growth abnormalities, your doctor may recommend a brace or, in severe cases, surgery.
• Chemotherapy: This treatment is given for malignant tumors. Chemotherapy destroys cancer cells.
• Radiation therapy: Radiation therapy can be used to control tumor growth in cancers such as breast cancer, soft tissue cancer called sarcoma, malignant peripheral nerve sheath tumors (MPNST), or glioma (a brain tumor).

If your hearing or vision is affected by NF, your doctor may recommend assistive devices such as hearing aids or corrective lenses.

Are there any side effects of the treatment?

Every treatment can have some side effects. Your doctor will talk to you about these side effects before you start treatment.

Possible side effects of surgery:

• Bleeding.
• Infection.
• Neurofibromas coming back after removal.
• Nerve damage.

Side effects of chemotherapy:

• Fatigue.
• Diarrhea or constipation.
• Hair loss.
• The food is tasteless.
• Nausea and vomiting.

What is the life expectancy of someone with Neurofibromatosis (NF)?

Neurofibromatosis (NF) usually doesn't have a significant impact on your life expectancy. However, depending on the location of the tumors, some of your daily activities, such as hearing and vision, may be difficult to do without assistance. If left untreated, some complications, such as cancer, can be life-threatening.

Can Neurofibromatosis (NF) be prevented?

There is currently no known way to prevent NF. If you are planning to start a family, it is a good idea to talk to a genetic counselor to learn more about the risk of having a child with a genetic condition.

When should I see a doctor?

See a doctor if you or your child notice any of these NF symptoms on their skin:

• Having six or more café au lait spots.
• Skin lumps appear for no reason.
• Having spots in the armpits or groin.

Other symptoms that require seeing a doctor:

• Changes in your hearing and/or vision.
• Pain without reason.
• Muscle weakness.
• Numbness or tingling in the fingers and toes.

If you have NF, your doctor will likely recommend that you come in for regular checkups (usually every 6 to 12 months) to monitor your symptoms. Be sure to schedule an additional appointment if you develop new symptoms or if an existing symptom gets worse.

What questions should I ask my doctor?

• What is causing my symptoms?
• What is the risk of my future children inheriting this condition?
• What kind of treatment do you recommend?
• Are there any side effects of the treatment?
• How often should I come for follow-up tests?
• Are there any clinical trials I can access?
• Should I see a fertility specialist?

Neurofibromatosis is a condition that affects your nervous system and skin. It can affect you in different ways. You may have symptoms that interfere with your daily activities, or you may have no symptoms at all. Often, depending on how your symptoms develop as you get older, it can take years to get an official diagnosis. Once you get this diagnosis, knowing exactly what's going on can be a huge relief. Your medical team can help you learn more about how this condition can affect you and possibly your future family. Although there is no cure, there are treatment options.

The most important thing to remember (Take-Home Message)

Neurofibromatosis (NF) is not something to be afraid of, but it is something to be aware of.

• If you have unusual spots, lumps on your skin, or a lot of spots in your armpits/groin, see a doctor .
• There are different types of NF, and the symptoms are different for each.
• This is a genetic condition, but it doesn't always run in families.
• Although there is no cure, there are many treatments available to help control symptoms and live a better life .
• It is very important to receive treatment under the supervision of a specialist medical team.
• It is essential to have regular medical checkups and be alert to new symptoms.

If you have any further questions about this, don't hesitate to talk to your doctor. They will be happy to help you.

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