Introduction

Neurofibromatosis is a condition that arises from the distortion of specific genetic information. This causes multiple brain and skin-related complications (in most cases from birth) including tumours. These tumours are mainly non-cancerous but can become cancerous depending on other factors. Genetic information is essential for an organism to develop and function properly. It is passed by parents to the next generation and stored in the Deoxyribonucleic Acid (DNA).¹ Each person has a unique DNA sequence; whenever any change occurs in this sequence, referred to as a mutation, the body may function abnormally.^{1, 2} This happens in Neurofibromatosis and is followed by uncontrolled cell growth and tumour formation.^3,4,5

Neurofibromatosis affects the population irrespective of ethnicity, race or even gender. Neurofibromatosis is categorised into three types:

1. Neurofibromatosis type I (NF1)
2. Neurofibromatosis type II (NF2)
3. Schwannomatosis (SWN)

The most common is NF1, which affects over 96% of people with neurofibromatosis and is characterised by a type of mark on the skin surface. Furthermore, other issues linked to the heart, back and the ability to concentrate are also seen.

NF2 is observed in approximately 3% of the people suffering from neurofibromatosis. It is characterised by problems related to the ears, balance and eyesight. Additionally, some people with NF2 may experience loss in muscle mass.

The least common type of neurofibromatosis is SWN, which affects around 1% of people with neurofibromatosis and has characteristics similar to NF2. 

NF1 affects people from birth, while the other two types of neurofibromatosis become evident as age progresses. Regular checkups can help the person affected become aware of the severity of the condition and manage their symptoms.

A few advanced techniques such as gene therapy are instilling hope in people for a neurofibromatosis cure.⁶

Types of neurofibromatosis that affect children and their symptoms

Neurofibromatosis found in children is the same for adults NF1, NF2 and SWN. They have the same symptoms however they have some that are different.

Neurofibromatosis type I (NF1)

Neurofibromatosis type I (NF1), also known as Von Recklinghausen disease, amongst all three, is one of the most widespread genetic disorders. Although it affects people right after birth, one-third to half of the people with neurofibromatosis acquire it after birth. Additionally, 1 out of 3,500 newborns suffers from this condition. 

There are many symptoms of NF1, some are:

• Café au lait spots: These are light brown patches found across the skin. These congenital (from birth) marks can have a diameter of around half a centimetre. The marks themselves are not threatening, but their presence suggests the existence of the mutated gene in the body.
• Bumps on the skin: These measure almost the same size as a pea. In a few cases, they may be larger and non-cancerous bumps present, formed by nerves in the spine and brain. These bumps become visible during or after adolescence but can be present since birth.
• Small brownish spots on the armpits or groin: This sign appears within the first five years of life.
• Pigmented Nodular growth in the iris of the eyes: This is also known as Lisch nodules or iris hamartomas. They happen during later phases of childhood but they are harmless and do not cause any vision issues.
• Optic nerve glioma: This is a type of tumour found in the region of the nerves that connect the eyes to the brain. It becomes evident at the age of 6 and can affect vision but most are asymptomatic. 
• Bone deformities: Unusual development of the tibia, which connects the knee with the ankle region and the sphenoid, the eye socket.
• Children with NF1 usually end up shorter but with larger heads. They also have cardiovascular complications like high blood pressure and suffer often from seizures.
• One of the most important aspects of NF1 is that it affects a child's ability to focus whilst performing an activity and makes them unable to comprehend the three-dimensional arrangement of an object or their surroundings.^3,9

Neurofibromatosis type II (NF2)

• NF2 is less common than NF1 as it affects one out of 40,000 newborns.¹¹
• Everyone has a “special” layer of cells that surrounds and protects the brain, however, those with NF2 get numerous non-cancerous tumours on this layer that cause multiple complications related to the brain, spinal cord and skull. 
• NF2 drastically affects a person’s vision and hearing ability. Issues related to balance are also observed
• Those affected by NF2 might feel a lack of sensation and weakness on the sides of their body. In a few cases, loss of muscular mass has also been reported.³

What causes neurofibromatosis?

To manage the growth of cells, a special kind of complex molecule, called neurofibromin, is found in the genetic information of the human body.³ Whenever any mutation, i.e. change in the sequence of the genetic information, happens in the gene which controls neurofibromin; the protein’s function is altered leading to uncontrollable cell growth.^9,10 This renders the formation of non-cancerous tumours at any specific site in the body. However, in some cases, these tumours reach a cancerous stage.^3,4,5,6 Moreover, mutations are not always inherited from parents and can spontaneously appear in someone’s DNA sequence. Nonetheless, the mutation is likely to be passed on to the children in almost 50% of the cases.³

How is neurofibromatosis diagnosed?

Along with all the symptoms, the doctor asks about the presence of NF1 or NF2 in any family members, especially parents. Then, to distinguish the symptoms from other medical conditions, a doctor may work in collaboration with another specialist, for instance, a doctor who specialises in the eyes. They can confirm if the vision-related issues, like nodular growth in the coloured part of the eyes, are because of Neurofibromatosis. ⁵ Furthermore, a genetic expert can identify the issue by finding the change in the person’s genetic information to confirm the presence of Neurofibromatosis. Other techniques such as MRI, blood tests and X-ray scans can also be useful for confirming the disorder.^7,8,12

Treatment of neurofibromatosis

Neurofibromatosis cannot be cured, so treatment is based on improving the symptoms of those affected by this disease. Skin spots generally do not need any treatment as they disappear over time. In comparison, skin bumps, which are nerve-related yet non-cancerous, are removed through surgery. For those who develop scoliosis due to neurofibromatosis, it can be treated through lifestyle changes or with surgery. Due to current technological advancements, gene therapy may hold some hope for future treatment of neurofibromatosis.³

How to manage neurofibromatosis

The most important way to manage neurofibromatosis in children is to have regular checkups, especially whole-body MRI scans that are helpful in the confirmation of NF1. Additionally, to help manage its symptoms:¹²

• A detailed skin examination
• Issues related to eyesight should be handled with serious care
• Hearing and balance-related problems must not be ignored
• The behaviour of the person with neurofibromatosis should be evaluated regularly, family support can also help the affected child
• Assessment of physical development is certainly crucial
• If a child is struggling to learn new things, a child psychologist might be helpful
• If a rise in blood pressure is observed in a child with Neurofibromatosis, then exercise and a healthy diet might help^3,6

Summary

Neurofibromatosis is a genetic condition that causes multiple brain and skin-related issues, which start as non-cancerous and may later become cancerous tumours. Genetic mutations occur during pregnancy and hence are transferred from parent to child. It causes various complications such as dark patches or spots on the skin, vision problems, hearing and balance concerns, focus and learning issues, problems related to various bones in the body, and many more. Neurofibromatosis cannot be cured, however, its symptoms can be treated or managed. With the advancement in technology, it may be possible to correct the mutation, which could cure neurofibromatosis.