Generality
Neurofibromatosis type 2 is a genetic, sometimes hereditary disease that arises due to a mutation of the NF2 gene and causes acoustic neuromas, benign skin tumors, benign tumors of the genus schwannoma, benign tumors of the ependymoma genus and benign tumors of the genus meningioma.
Brief review of neurofibromatosis
Neurofibromatosis is the name of a particular group of genetic and, sometimes, even hereditary, conditions that alter the normal processes of growth and development of nerve cells and determine the onset of tumors mostly benign at brain level, spinal cord, nerves cranial and peripheral nerves.
To be precise, in the neurofibromatosis group there are three diseases, different both in their causes and in their symptoms, whose names are: type 1 neurofibromatosis, type 2 neurofibromatosis and schwannomatosis.
What is neurofibromatosis type 2?
Neurofibromatosis type 2, or NF2, is the neurofibromatosis resulting from a very precise mutation of the NF2 gene, located on chromosome 22 .
Epidemiology
According to statistics, one person every 35, 000 would be born with type 2 neurofibromatosis.
In a scale related to the prevalence of neurofibromatosis in the general population, neurofibromatosis type 2 is located in the middle, under neurofibromatosis type 1 (which is the most common) and above schwannomatosis (which is the most rare).
Causes
As anticipated, type 2 neurofibromatosis is due to a specific mutation of the NF2 gene, located on chromosome 22.
In a person, the aforementioned mutation can be hereditary - that is, transmitted by one of the parents - or acquired spontaneously during embryonic development - that is, after the fertilization of the oocyte by the spermatozoon and during the process of embryogenesis.
Type 2 neurofibromatosis, therefore, is part of the genetic diseases that can also be hereditary.
What are the functions of NF2? What happens when it has changed?
Premise: the genes present on human chromosomes are DNA sequences that have the task of producing fundamental proteins in biologic processes indispensable to life, including cell growth and replication.
Under normal conditions (ie when there are no mutations), the NF2 gene produces a protein called merlina or schwannomina, whose function is to regulate the growth of nerve cells.
The NF2 mutation that leads to type 1 neurofibromatosis results in the failure to produce merlin and an abnormal proliferation without control of nerve cells (because it is less a fundamental regulator of their growth).
It is precisely because of this abnormal proliferation and without control of the nerve cells that benign tumors typical of type 2 neurofibromatosis are formed.
Is the hereditary form or the non-hereditary form more common?
Hereditary type 2 neurofibromatosis is as common as, more or less, non-hereditary neurofibromatosis type 2; indeed, statistical studies have shown that the number of hereditary cases is approximately equal to the number of non-hereditary cases.
Inheritance of neurofibromatosis type 2
Type 2 neurofibromatosis is an example of an autosomal dominant disease ; for an inexperienced reader of genetics, this means that:
- A parent carrying the mutation is sufficient to have the disease in question in part of the offspring;
- The disease and its symptoms are also manifested in the presence of only one mutated gene allele (no matter whether maternal or paternal), as this mutated allele is always dominant over the healthy one;
- The probability that a couple, in which only one of the two components is the carrier of the mutation responsible for the disease, generates a sick child is equal to 50%.
Symptoms and complications
Typically, type 2 neurofibromatosis demonstrates itself with characteristic symptoms and signs towards the end of adolescence .
The complete NF2 symptomatology includes:
- Hearing and balance problems;
- Skin plates;
- Problems related to the presence of schwannomas;
- Problems related to the presence of ependymomas;
- Problems related to the presence of meningiomas.
Hearing and balance problems
Particularly benign brain tumors, known as acoustic neuromas or vestibular schwannomas, cause hearing and balance problems . The acoustic neuroma, in fact, is a neoplasm that affects and functionally alters the VIII cranial nerve (or vestibulocochlear nerve ), that is one of the main nerve structures responsible for controlling balance and hearing.
In addition to causing hearing and balance problems, the presence of acoustic neuromas is often also responsible for other symptoms, including: tinnitus, dizziness, vomiting, dysphagia, facial numbness and vomiting.
The acoustic neuroma is, by far, the most common type of benign tumor in neurofibromatosis type 2 patients; in fact, its response occurs in more than 90% of clinical cases.
Skin plates
Skin plates are benign tumors of the skin, belonging to the category of neurofibromas, which measure at most 2 centimeters in diameter and are of a typical dark color.
Present in about half of patients with type 2 neurofibromatosis, skin plaques are primarily an aesthetic problem.
If they grow close to important nerves, skin plaques may be responsible for pain.
Problems related to the presence of schwannomas
A schwannoma is a benign tumor that originates from the Schwann cells of the nerves of the peripheral nervous system (cranial nerves, spinal nerves, etc.).
In those suffering from NF2, schwannomas can affect a variety of nerves and cause symptoms such as:
- Vision problems, including an early form of cataract (juvenile cataract);
- Numbness and tingling in various parts of the body;
- Weakness of the facial muscles;
- Lack of coordination;
- Neuropathic pain.
Problems related to the presence of ependymomas
An ependymoma is a benign or malign brain and spinal cord tumor that originates from so-called ependymal cells .
In NF2 carriers, ependymomas are generally benign, capable of causing lower back pain, muscle weakness and numbness in the arms and legs.
Problems related to the presence of meningiomas
A meningioma is a benign tumor of the brain, which grows at the level of the meninges .
In patients with NF2, the presence of meningiomas may be responsible for: headache, vomiting, epilepsy, double vision, sudden personality changes, reduced vision, speech impairment, lack of memory, etc.
Statistical studies say that ependymomas are tumors that characterize about half of the cases of type 2 neurofibromatosis.
Complications of type 2 neurofibromatosis
Type 2 neurofibromatosis can give rise to several complications, including:
- Complete deafness. It is due to a worsening of one or more acoustic neuromas;
- Facial paralysis. It depends on severe schwannomas of the VII cranial nerve (or facial nerve), which is responsible for controlling the muscles of the face.
Sometimes, it is a complication of the acoustic neuroma;
- Fall in sight. It is a consequence of juvenile cataract;
- Peripheral neuropathy. It is the result of the possible damage schwannomas can cause to peripheral nerves, in an advanced phase of type 2 neurofibromatosis.
Peripheral neuropathy causes symptoms such as pain, tingling and muscle weakness at the level of the limbs;
- Formation of malignant neoplasms starting from benign ones. It can affect skin plaques, but also ependymomas.
Diagnosis
As a rule, the diagnostic procedure for the detection of type 2 neurofibromatosis includes:
- A careful objective examination, to delineate the symptomatic picture;
- A thorough history, to understand the possible causes of the symptoms;
- Investigations on the family history of the patient, to clarify whether the present pathological condition may have an hereditary origin or not;
- Acoustic tests, to assess the degree of impairment of the hearing subject's faculty;
- Eye exams, to look for problems like cataracts;
- Radiological examinations, such as X-rays, CT and nuclear magnetic resonance, referred to encephalon, spinal cord and peripheral nerves, to confirm the presence of benign tumors only previously suspected, based on the present symptoms;
- A genetic test to obtain diagnostic confirmation.
Curiosity
Currently, there is the possibility of carrying out a genetic test, for the research of neurofibromatosis type 2, also in prenatal age; clearly, a similar genetic test is indicated only if there is a concrete risk of NF2 (eg: one of the two parents carries the disease in question).
When does an individual suffer from type 2 neurofibromatosis? The diagnostic criteria
According to the medical community, an individual suffers from type 2 neurofibromatosis, if he falls into one of these four situations:
- Bilateral acoustic neurinoma, ie present on both vestibulocochlear nerves;
- Family history of NF2 combined with unilateral acoustic neuroma or the presence of at least two meningiomas, ependymomas, skin plaques and schwannomas, and the presence of cataracts;
- Unilateral acoustic cataract neurinoma combined with at least two meningiomas, ependymomas, schwannomas and skin plaques;
- Two or more meningiomas combined with monolateral acoustic neuroma or cataract and at least two ependymomas, schwannomas and skin plates.
Therapy
Type 2 neurofibromatosis is an incurable disease.
However, this aspect does not exclude that there are treatments aimed at alleviating the symptomatology ( symptomatic therapy ) and therapeutic approaches with preventive aims towards the numerous possible complications.
How to prevent the worst complications?
The prevention of the most serious complications of type 2 neurofibromatosis is based on periodic monitoring of skin plaques, visual problems and brain tumors, especially ependymomas. The periodic monitoring of the aforementioned problems, in fact, allows the early identification of any deterioration, so as to remedy it, with an ad hoc treatment, before the situation degenerates beyond all limits.
Important
For patients with NF2 or those who care for them, experts recommend contacting the doctor immediately whenever there is a sudden and significant deterioration in symptoms.
Symptomatic therapy
Symptomatic therapy against neurofibromatosis type 2 includes:
- Removal of the acoustic neuroma or of neuromas . Currently it is possible to provide for the removal of an acoustic neuroma by means of a traditional surgery or through the so-called stereotactic radiosurgery;
- The installation of a cochlear implant, to restore the sense of hearing in patients in whom the acoustic neuroma (or the intervention for its removal) has had serious consequences on the hearing faculties;
- Cataract surgery, aimed at restoring at least part of the patient's visual abilities;
- Pharmacological treatment against peripheral neuropathy . Drugs for peripheral neuropathy include antiepileptics (gabapentin or pregabalin), antidepressants (amitriptyline or nortriptyline), opioid-type painkillers and capsaicin in cream;
- Radiation therapy against tumors transformed into malignant and non-surgically removable;
- Pharmacological treatment against epilepsy . Medicines for epilepsy from type 2 neurofibromatosis include topiramate and carbamazepine.
Prognosis
Type 2 neurofibromatosis is a condition that is not only incurable, but also potentially very debilitating; therefore, in his presence, the prognosis can never be positive.
However, it is important to recognize that current symptomatic treatments and periodic monitoring of health status can be of considerable help to patients, appreciably improving their quality of life.
Prevention
Type 2 neurofibromatosis is an impossible condition to prevent.
