Schwannomatosis and NF2

About schwannomatosis and NF2

There are many different types of schwannomatosis (SWN), each designated by its specific
genetic variant. To date, the following types are known:

  • NF2-related schwannomatosis
  • Schwannomatosis linked to SMARCB1
  • LZTR1-linked schwannomatosis
  • 22Q-linked schwannomatosis
  • Schwannomatosis NOS (not otherwise specified)
  • Schwannomatosis NEC (not classified elsewhere)

SWN is the least common and most recently identified form of NF. SWN is a generic term for
several genetic conditions that cause benign tumours to develop on the nerves.
Approximately one in 20,000 births will eventually be diagnosed with schwannomatosis (all
types), and one in 70,000 people will be diagnosed with NF2-related schwannomatosis
(NF2-SWN).

SWN is a genetic disease caused by pathogenic variants of a gene located on chromosome 22. The signs and symptoms of SWN generally develop between adolescence and adulthood, although they can occur at any time. The disease affects all populations, sexes, and ethnic groups equally.

Symptoms of SWN

As the name suggests, the most common tumours are called schwannomas. Individuals will develop these benign tumours on the nerves of the central nervous system (brain, spine) and on the peripheral nerves, which are the nerves of the rest of the body. These tumours develop when Schwann cells (part of the envelope called the nerve sheath, which insulates the nerves) grow abnormally. These tumours can affect patients in a number of ways, such as hearing loss, eye problems or pain that can be difficult to manage. There are at least three genes, NF2, LZTR1 and SMARCB1, known to cause schwannomatosis, and more genes may be discovered in the future. These genes are thought to help regulate cell growth and division. Cells can multiply excessively and form tumours if these genes don’t work properly.

Depending on the type of schwannomatosis, a common symptom is chronic pain, which can occur anywhere in the body. It is thought to be caused at least in part by schwannomas pressing on the nerves.

Treatments for SWN

Although there is currently no official cure for schwannomatosis, and no drug has been shown to be effective in treating schwannomas, promising advances have been noted in ongoing research. However, pain management is generally an integral part of care. People with schwannomatosis are best served in an NF clinic, where multidisciplinary specialists experienced in schwannomatosis can administer pain management protocols that have proven effective for people with this disease. In addition, the psychological impact of living with chronic pain can lead to depression and anxiety, which must be monitored in any individual with schwannomatosis.

NF2-related schwannomatosis (NF2-SWN)

NF2-related schwannomatosis (NF2-SWN), otherwise known as neurofibromatosis type 2, affects around one in 25,000 people worldwide. As mentioned above (schwannomatosis section), it is a genetic disease caused by pathogenic variants of a gene located on
chromosome 22. It manifests as non-cancerous (benign) tumours called vestibular schwannomas on the eighth cranial nerve, which is the nerve that carries sound and balance information to the brain. Like NF1, NF2 schwannomatosis is inherited from one parent in half
of all cases. In the other half of patients, NF2-related schwannomatosis occurs without a parent: in this case, the sufferer is said to have contracted the genetic disorder through spontaneous mutation. What’s important to know is that people with this type of NF, whether they inherited it from a parent or contracted it through spontaneous mutation, have a 50% chance of passing the disorder on to each of their children.

Symptoms of NF2-SWN

Like NF1, NF2-related schwannomatosis causes symptoms that vary widely from patient to patient. In most sufferers, the first symptoms appear in early adulthood, towards the end of adolescence. However, in 1 in 10 patients, symptoms appear in late childhood.

Schwannomatosis linked to NF2 can manifest itself as mild symptoms, meaning that symptoms may be present in a person for many years before the true nature of the problem is detected, or as more severe symptoms, even within the same family.

Patients with this type of NF are at high risk of developing not only auditory nerve tumours (vestibular schwannomas), but also brain tumours (meningiomas), spinal cord tumours (meningiomas or ependymomas) and eye symptoms. To shed some light on all these
tumour types, let’s take a closer look at the symptoms they can cause.

Symptoms related to brain tumours (meningiomas)

  • Epileptic seizures
  • Various problems depending on the location of the tumour, e.g. headache, weakness or reduced sensation

Symptoms related to auditory nerve tumours (vestibular schwannomas)

This nerve is linked to hearing and balance. Most often, sufferers develop tumours on the auditory nerves on both sides. Symptoms include:

  • Hearing impairment or loss
  • Tinnitus (ringing in the ears)
  • Balance problem
  • Sagging face (facial asymmetry) caused by facial muscle weakness
  • Difficulty swallowing (dysphagia)

Symptoms related to spinal cord tumours (meningiomas or ependymomas)

  • Weakness or reduced sensation in arms or legs
  • Leaking urine or stools

Eye symptoms

  • Loss of sight
  • Reduced vision due to various causes, such as cataracts

Hearing or visual loss and balance disorders are really the main consequences of NF2-SWN.

If you ever experience one or more symptoms resembling NF2 schwannomatosis, it’s very important to tell your family doctor, who will be able to refer you to an NF specialist.

Should you need to consult a team of NF specialists, they will determine whether you have the disease on the basis of a number of criteria, such as the various symptoms you have, whether the disease runs in your family, and so on. If requested, you may even undergo a
genetic test to determine whether there is a mutation in the NF2 gene.

Treatments for NF2-SWN

Currently, the only treatments available for NF2 tumours are surgery, certain drugs or radiotherapy. The majority of people with NF2 will undergo at least one surgical procedure at some point in their lives.

However, patients with NF2-related schwannomatosis have recourse to one of these treatments only if the tumours are causing significant disorders. The aim is to reduce the size of the tumours or eliminate them.

Some targeted therapies, and rarely radiotherapy, can slow or even stop tumour growth. Provided the patient has one or more non-operable, non-cancerous tumours, they may benefit from these treatments.

Pain management is also usually an integral part of care in patients with tumours that cannot be surgically removed.

If, after reading this information, you have any doubts about your condition, don’t hesitate to seek medical advice! If you are ever diagnosed with NF2, the sooner you are treated, the less likely you are to suffer serious complications.