What is Neurofibromatosis Type 2?
Neurofibromatosis type 2 (NF2) is a genetic disorder that one can inherit from their parents. This condition is marked by the growth of multiple tumors within the central nervous system, which includes the brain and spinal cord. It’s important to understand this condition to properly manage it and maintain a good quality of life.
What Causes Neurofibromatosis Type 2?
The condition known as NF2 can be inherited from parents in some patients. It acts like a dominant trait, which means only one copy of the faulty gene is needed for the disease to occur. This gene can come from either the mother or the father, and there’s a 50% chance of a parent passing on the gene to their children.
However, not everyone with NF2 has a family history of the disease. In some cases, the disease is caused by a new mutation in the NF2 gene that wasn’t present in the genes of the parents.
The NF2 gene is found on chromosome number 22 and its role is to provide instructions for making a protein called merlin. This protein acts as a tumor suppressor, which means it helps control cell growth and prevent tumors from forming. Specifically, merlin is found in special cells called Schwann cells, which are part of the nervous system. When the NF2 gene is faulty, this can lead to the development of NF2.
Risk Factors and Frequency for Neurofibromatosis Type 2
The condition known as NF2 is not very common, it affects approximately 1 out of every 25,000 to 40,000 people.
Signs and Symptoms of Neurofibromatosis Type 2
Neurofibromatosis type 2 (NF2) is a condition that often starts showing symptoms when a person is around 20 years old. The most common symptom is the development of a type of brain tumor called vestibular schwannoma. These tumors often develop on both sides of the brain in people with NF2. Symptoms of these tumors could include ringing in the ears, loss of hearing, and balance problems.
NF2 can also cause changes to the skin. The most common change is the development of raised, often darker, patches on the skin. Other changes can include tumors beneath the skin, which are usually schwannomas rather than neurofibromas.
There are also cases of people with NF2 developing meningiomas, which are tumors that grow on the tissue that covers the brain and spinal cord. These tumors can cause headaches, seizures, and neurological symptoms depending on where they are located. People with NF2 tend to develop meningiomas earlier in life compared to people with sporadic meningiomas. In fact, around 20% of children with meningiomas have NF2.
In addition to these symptoms, people with NF2 may have an increased risk of developing tumors on their spinal cord which may cause pain, muscular weakness and paresthesia (tingling or prickling sensations).
Diagnosis of NF2 is based on certain criteria, which include he presence of:
- Bilateral vestibular schwannomas (tumors on both sides of the brain) in patients under 70
- Single (unilateral) vestibular schwannoma in patients under 70 who have a direct relative with NF2
- At least 2 of the following as well as first-degree relative with NF2 or negative LZTR1 testing: meningioma, schwannoma (non-vestibular), neurofibroma, glioma, cerebral calcification, cataract, or single (unilateral) vestibular schwannoma
- Mutliple meningiomas and either a unilateral vestibular schwannoma, or at least two of the following: schwannoma (non-vestibular), neurofibroma, glioma, cerebral calcification, cataract
- Demonstration of NF2 gene mutation through blood test or identification of an identical mutation from two separate tumors in the same individual
Testing for Neurofibromatosis Type 2
If your doctor suspects you have Neurofibromatosis type 2 (NF2), a genetic disorder that causes tumors to form on nerve tissue, they will need a detailed overview of your clinical and family history. A physical examination will be conducted to check for skin tumors or plaque-like lesions. Your doctor will also conduct an eye examination looking for cataracts and any issues with your optic nerve.
To further investigate the presence of tumors, your doctor will employ Magnetic Resonance Imaging (MRI), an imaging technique used to create detailed images of the organs and tissues within your body. MRI helps your doctor to evaluate the condition of schwannomas (tumors that occur on nerve sheaths) and meningiomas (tumors that occur in the membranes surrounding the brain and spinal cord).
In the case of vestibular schwannoma, a particular type of nerve tumor, your MRI would reveal it residing in the internal auditory canal, sometimes causing the canal to widen. Larger tumors may extend into the area where your brain connects with your spinal cord, creating an “ice cream cone” appearance. On your MRI images, these tumors appear less intense on T1-weighted images and more intense on T2-weighted images, with intense contrast enhancement.
Meningiomas are common brain tumors that materialize outside the brain. People with NF2 usually develop these at an earlier age, and they tend to have multiple occurrences. If meningiomas are detected in children, NF2 diagnosis is usually considered. On MRI, they appear like dural-based lesions (lesions on the outer layers of the brain and spinal cord) and exhibit intense enhancement.
In patients with NF2, multiple spinal tumors, including schwannomas, meningiomas, and ependymomas, can be diagnosed with MRI. Schwannomas are most common and usually emerge from the upper part of the spinal cord, giving them a dumbbell-like shape. Meningiomas and ependymomas display typical appearances, largely visible in the neck or upper functioning region of the spinal cord.
Treatment Options for Neurofibromatosis Type 2
Patients with Neurofibromatosis Type 2 (NF2), a condition that causes noncancerous tumors to form along the nerves, need to be managed by a team of different doctors. This includes cancer specialists (oncologists), nerve specialists (neurologists), doctors who specialize in using imaging technologies to detect diseases (neuroradiologists), eye doctors (ophthalmologists), experts on inherited medical disorders (geneticists), and specialists who treat nervous system diseases with surgery (neurosurgeons).
To track the progress of any tumors, it’s recommended that patients have a brain MRI scan every year. If no tumor is found in the initial scan, then they can have one every two years. If a tumor is found, they should get an MRI twice in the first year, and then once a year after that.
If small tumors known as vestibular schwannomas are found but aren’t causing any symptoms, these can be monitored with routine MRI scans. If these tumors become large and start to cause problems, surgery is the main treatment. Meningiomas, another type of tumor, are traditionally treated with surgery as well. If someone isn’t fit for surgery, radiation therapy may be used instead. Meanwhile, tumors on the spinal cord, known as ependymomas, are usually less severe and can be observed over time. Surgery is only needed if these tumors start to cause symptoms.
A new treatment option for many types of tumors is an immunotherapy drug called Bevacizumab. It’s a type of lab-made antibody that seeks out and blocks a protein called vascular endothelial growth factor (VEGF) that helps tumors to grow. Some researchers have found that this treatment can lead to a decrease in the size of the tumors and an improvement in hearing in NF2 patients.
What else can Neurofibromatosis Type 2 be?
When diagnosing Neurofibromatosis type 2 (NF2), it’s important to distinguish it from another condition – Schwannomatosis. This is a different type of neurofibromatosis, separate from NF1 and NF2. Usually, Schwannomatosis isn’t inherited and appears randomly in around 80% of cases, but in 20% of cases, it does run in families. Unlike NF2, Schwannomatosis involves the formation of multiple schwannomas (tumors in the protective lining of nerve cells) in the peripheral nervous system, specifically avoiding the vestibular nerves that link the inner ear with the brain. Schwannomas that aren’t located in the vestibular nerves are quite rare but can also occur in patients with Schwannomatosis.
What to expect with Neurofibromatosis Type 2
The future health of these patients is uncertain. If the tumors are found late, the results are not good, and the quality of life is decreased.
Possible Complications When Diagnosed with Neurofibromatosis Type 2
Possible complications from a brain tumor can vary, and often depend on how close the tumor is to important parts of the brain. Some of the potential issues that might come up include:
- Muscle weakness
- Hydrocephalus (a buildup of fluid in the brain)
- Deficits in cranial nerves (problems with the nerves that control sight, smell, taste and other functions)
Preventing Neurofibromatosis Type 2
Doctors should ensure that the patient fully understands everything about their health condition, including potential complications, and how hard it might be to completely cure it. If the condition is genetic, then talking with a genetics counselor before deciding to have a baby could help them make the best decisions for their health and that of their future child.
