Neurofibromatosis – Types, Symptoms, Causes, Diagnosis and Treatment


A genetic disorder of the nervous system, neurofibromatosis (NF) affects the formation and growth of nerve cells. This disorder brings about the growth of tumours on the nerves in the human body. People tend to get this disorder either from their parents or when a mutation takes place in the genes. Most of the time, people who possess it, pass it on to their children. Generally, these tumours are benign, however, they can turn cancerous (malignant) in some rare cases .

The last day of February is celebrated as Rare Disease Day globally, so on this Rare Disease Day (February 28), let's understand the genetic rare disorder neurofibromatosis, its types, symptoms, causes, diagnosis and treatment methodology.

Neurofibromatosis is a rare kind of genetic disorder. This ailment causes benign tumours of the nerves in various parts of the body. Although, only a few people with this disorder show signs of neurological problems, most of the others seem to be superficially affected .

This disorder is usually diagnosed during childhood or early adulthood. Most of the time, the symptoms are mild but however, there could be complications that can lead to learning impairment, heart problems, loss of vision and hearing loss.

There are basically three kinds of neurofibromatosis disorders. These are neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis. These are genetic disorders that are complex in nature and can affect different organs of the body. The most common attribute of these disorders is the tendency for noncancerous tumours to develop on the spine, brain, nerves and skin. Nevertheless, the severity of the symptoms could vary from person to person .

The focus of the treatment lies with the aim of encouraging healthy growth in children. Early management of complications can provide great relief. Surgery is the choicest treatment option when large tumours press on a nerve. Therapies such as stereotactic radiosurgery can also be effective in managing the symptoms.

This is the most common kind of neurofibromatosis and one of the most common genetic conditions that is observed in at least 1 in 3,000 births. In most of the cases, this condition is inherited from a parent. In the rest, the ailment occurs as a result of a mutation (either new or spontaneous) or when there is a loss of a part of the neurofibromatosis 1 gene.

As we know, the human cells are made up of 23 chromosomes (these house genetic information). The neurofibromatosis 1 gene is present on the 17th chromosome. A protein called neurofibromin is produced by the gene. This is responsible for multiple functions such as regulating cell growth and improving the health of the brain and the bone.

The symptoms of this disorder vary from person to person and even among family members who possess this condition.

The most common signs of this disorder are the brown, flat spots on the skin. These are referred to as the café-au-lait spots . They are usually present from birth. With age, there could be an increase in size and number. Sometimes, they fade away later in one's life. People with this condition will ideally have multiple spots.

People with this condition could also show signs of freckling around the armpit and groin region. This usually becomes pronounced with age.

Occurrence of neurofibromas is also common with this condition. Neurofibromas are non-cancerous, slow-growing tumours. These ideally develop in the protecting covering of nerve cells (nerve sheath). The following are the three main types of neurofibromas and their respective features:

Some of the other aspects of neurofibromatosis type 1 that need to be considered are as follows.

Less common than type 1, neurofibromatosis type 2 occurs in about 1 in 40,000 births. Only a few people with this condition possess café-au-lait spots (seen in type 1 patients). People with type 2 have higher chances of developing tumours on the eighth cranial nerve (located on the sides of the head and responsible for transmitting hearing and balance signals from ears to the brain).

The tumours in the eighth cranial nerve are also known as acoustic neuromas or vestibular schwannomas. This causes problems with balancing, progressive hearing loss and ringing-like sensation in the ears.

When tumours occur on other cranial nerves, it could cause problems with swallowing and other issues such as facial weakness, double vision and facial numbness. They can occur on nerves throughout the body. They develop from Schwann cells and are therefore also referred to as schwannomas.

Meningiomas are also common in people with the type 2 condition and can cause tumours to arise from the linings of the brain and spinal cord.

A rare form of cataract - subcapsular lenticular opacity - causes clouding of the lens in the eye and is common in people with NF2.

This rare form of neurofibromatosis was first observed in the year 1990. It affects about 1 in 40,000 people. People with this ailment, develop multiple schwannomas. This involves tumours that consist of Schwann cells. People with this condition, do not develop other types of tumours such as meningiomas, ependymomas or neurofibromas. This genetic condition occurs when there are changes in the genes INI1 and LZTR1.

When NF2 leads to the growth of schwannomas in the nerves of the body, then the following signs might be noticed:

Neurofibromatosis is caused by mutations that are either passed on by a parent or spontaneously occurred at conception. The gene involved in this genetic disorder depends on the type of neurofibromatosis.

NF1: The NF1 gene (located on chromosome 17) produces a protein known as neurofibroma. When a mutation occurs, the mutated gene causes a loss of neurofibromin. This leads to uncontrolled growth of cells .

NF2: The NF2 gene (located on chromosome 22) produces a protein known as merlin (which is responsible for suppressing tumours). When a mutation occurs, there is a loss of merlin. This leads to uncontrolled cell growth .

Schwannomatosis: Mutations of the genes SMARCB1 and LZTR1 (responsible for suppressing tumours) are the known cause behind schwannomatosis .

Apart from taking the medical and family history of the patient into consideration, the following tests are conducted to diagnose neurofibromatosis:

A person should possess at least two of the following symptoms to receive a diagnosis of NF1 :

To be diagnosed with NF2, a person must have

There is no cure available for this genetic disorder. However, treatment options available focus on controlling the symptoms. Moreover, many symptoms such as the presence of café au lait spots do not require any specific treatment. Nevertheless, when treatment becomes necessary, the following options are available :

The way a person's life progresses after the diagnosis of neurofibromatosis depends on the type of NF he or she has. Most of the times, the symptoms of NF1 are quite mild and people who have this disorder are able to lead a productive life in spite of the ailment and its associated symptoms. However, the problem arises when the pain and deformity due to the condition lead to significant disability. Regular checkup with the doctor along with possible treatment approaches can relieve the suffering caused due to the symptoms to a great extent .

In case of people with NF2, how well one leads the life after having this disorder basically depends on the person's age at onset of the disease and also on the number and location of tumours present. In some rare cases, it can be life-threatening .

People with schwannomatosis usually face severe pain and this can be very debilitating .

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