"Neurofibromatosis Type 2" – What Is It?
Neurofibromatosis type 2 (NF2) or central neurofibromatosis is a genetic, i.e., hereditary, disease that typically appears in young adulthood and is associated with the development of benign central nervous system tumors. A characteristic feature of patients with NF2 is the development of benign tumors of the 8th cranial nerve, typically on both sides, so-called bilateral vestibular schwannomas, formerly called acoustic neuromas. As the 8th cranial nerve supplies hearing and balance, these tumors increase hearing loss and sometimes balance disorders or gait instability. Other benign tumors, brain tumors, and spinal tumors can also occur. A deterioration in vision, triggered by a particular form of lens opacity (juvenile cataract), is also characteristic. NF2 is one of the tumor predisposition diseases.
How Is "Neurofibromatosis Type 2" Diagnosed?
Manchester Criteria for the Diagnosis of NF2
NF2 can be clinically diagnosed based on the following criteria:
- Bilateral vestibular schwannomas (VS)
or
a positive family history of NF2 (first-degree relatives= parents, siblings, children)
plus - Unilateral VSy
or
2 of the following: Meningioma/glioma/neurofibroma/swannoma/juvenile cataracts
Clinical Signs
Tinnitus (ringing in the ears) and increasing hearing loss in young adulthood are often the first symptoms that lead to a visit to the doctor. Balance problems, unsteady gait, headaches, numbness, or even paralysis of a facial nerve are also described.
Around 30% of patients develop symptoms in late childhood. At this age, initial symptoms are more often caused by benign tumors of the meninges (so-called meningiomas). Furthermore, damage to a nerve caused by schwannomas can lead to pain or loss of function. Sometimes, visual impairment caused by juvenile cataracts is the first sign that leads to a diagnosis.
The clinical signs are highly variable and subtle, with the first symptoms usually only appearing in young adulthood. Typical findings are listed below:
- Skin tumors are found in just over two-thirds of all patients. These are predominantly schwannomas, although neurofibromas are also rarely reported. These tumors present themselves in three forms:
-
- Plaque-like schwannomas within the skin, slightly raised, pigmented (more color), and increasingly hairy
- Nodular tumors under the skin, which may appear as a spindle-shaped, rough swelling
- Neurofibromas that are located directly in the skin
- The irregularly bordered café-au-lait stains (CALF) typical of NF1 are also found more frequently in NF2 than in healthy people but are far less pronounced than in NF1.
- Schwannomas, neurofibromas, meningiomas, and gliomas are benign tumors originating from cells surrounding, protecting, insulating, and nourishing the nerve, the so-called nerve sheaths.
- Juvenile subcapsular lens opacity (cataract) is a particular form of lens opacity that occurs in adolescence and can lead to a deterioration in vision.
What Is the Risk of Cancer?
Typical is the development of benign nerve sheath tumors, primarily schwannomas, which grow on both sides along the 8th cranial nerve and can lead to tinnitus (ringing in the ears), hearing loss, and impaired balance. These nerve sheath tumors also grow in other areas, e.g., along peripheral nerves in the skin or the central nervous system, brain, or spinal cord. Other benign tumors of the nervous system include meningiomas, astrocytomas, and low-grade ependymomas, which are located in the spinal canal and can cause pain and neurological deficits and lead to gait instability. Around half of these findings are diagnosed by chance and usually do not cause symptoms.
What Is Known About the Development of "Neurofibromatosis Type 2"?
Neurofibromatosis type 2 is a genetic disease caused by a mutation, a change in the genetic material—the affected gene codes for a merlin protein, sometimes known as schwannomin. Merlin is mainly found in nerve tissue and acts as a tumor suppressor, i.e., it counteracts tumor development by inhibiting growth.
NF2 occurs in about 1 in 25-33:000 people. Just over a third of the diseases are inherited and passed on from parents to their children; the inheritance is autosomal dominant. This means the probability of passing on the disease (inheritance) is 50%. Slightly less than 2/3 of diseases are due to a spontaneous or new mutation, known as a de novo mutation. This means that the genetic change has arisen in the patient themselves.
Genetic testing is possible and is recommended to confirm the diagnosis for all individuals with a clinical diagnosis and all patients with tumors typical of NF2 (meningiomas, schwannomas). Genetic testing of potentially affected but non-symptomatic family members is recommended from 10-12.
Is There Any Treatment Option Available?
In the case of growing vestibular schwannomas (VS) and impending hearing loss, surgery, and radiation are considered treatment options if the risk of increasing damage from the tumor itself is greater than the risk of surgery or radiation. In children, radiation should be avoided if possible, as there is a risk of so-called secondary tumors developing. In the rapidly growing VS, excellent treatment results are being achieved with a drug not yet approved in Germany for this indication, bevacizumab (trade name Avastin). A brainstem or cochlear implant can be considered in cases of deafness.
Diagnosis of " Neurofibromatosis Type 2" What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Diagnosis of " Neurofibromatosis Type 2" What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Medical Measures for Early Detection
The aim is to detect developing complications early to achieve the best treatment results. Regular medical check-ups are recommended for this purpose (AACR 2016 examination recommendations):
- Annual medical history and clinical check-up, audiometry (sound and speech audiometry)
- Annual cranial MRI (recommended twice a year in the year of diagnosis to record tumor growth rate) from the age of 10 (earlier in the case of high-risk genotype and clinical symptoms)
- Spinal MRI from the age of 10 every 2-3 years (as soon as tumor growth is detected, first check-up recommended after 6 months to record tumor growth rate)
- Consider whole-body MRI
- There is no recommendation for routine screening with F-FDG-PET/CT or MRI in the absence of symptoms
Neurofibromatosis Type 2 – What You Can Do Yourself
You Should Pay Attention to This
If you have the impression that your child’s hearing is worse in one or both ears if he or she complains of increased headaches, morning sickness, becomes tired quickly after reading, or complains of numbness or paralysis in the face (asymmetry of facial features), or if you notice a dropped hand or foot drop, please make an appointment with your eye specialist, pediatrician or in an NF special outpatient clinic.
Further Information
- Link to the website of the “Children’s Tumor Foundation”
- Link to German website of Neurofibromatosis Association
Patients can also register for the KPS register at any time or have this done by the doctors in charge.
Any further questions?
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