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Diseases and Disorders of the Ear

Inherited Hearing Disorders
Neurofibromitosis

Neurofibromatosis

There are two different types of neurofibromatosis: NF1 and NF2. Neurofibromatosis type 1, or von Recklinghausen’s disease, is the most common and is an inherited disorder whose symptoms are often displayed early in life.  NF2, a less common version, is also an inherited disease but develops later in life, usually starting in adolescence. This type causes non-cancerous tumors to develop. Both NF1 and NF2 are caused by different faulty genes, which may be inherited or may have spontaneously mutated during the development of the egg or sperm.

Causes of Neurofibromitosis NF2

People who are affected by NF2 have a change (mutation) in a gene that is located on chromosome 22. This gene has been called the NF2 gene and contains the information for cells to make a protein that normally stops tumor growth. Everyone has the NF2 gene but in people with NF2 the gene is faulty due to a mutation.

NF2 often affects ‘hearing’ nerves

The major feature of NF2 is the development of swellings (non-cancerous tumors) on the nerves that control hearing and balance (the auditory and vestibular nerves). The tumor that develops on the nerves is called a schwannoma. In the majority of cases, the schwannomas develop on both sides of the body (bilaterally) but not necessarily at the same time. This means the hearing loss may be of different degrees in both ears. In some cases, the schwannomas develop on only one side of the body (unilateral).

Other nerves may be affected

Different types of tumors in NF2 may affect other nerves in the body. This can impact on the control of:

Tumors may also occur in the central nervous system: that is, the brain and spinal cord.

NF2 develops later
Signs of NF2 usually develop in late adolescence but may not be obvious until adult life. Some people do not develop problems until their 40s or 50s.

NF2 genetic inheritance factors

If both parents are unaware of the NF1 or NF2 recessive genes carried by both parties, the first indication of this disorder is a gradual loss of hearing in a child. This condition may begin in adolescence for NS2 type and later in life for the NS1 type.

Often there is a family history of NF2: that is, other family members have the condition, particularly a parent. An affected parent has one chance in two (or a 50 per cent chance) in every pregnancy of passing the NF2 faulty gene on to their child.

Where there is no family history and the diagnosis of NF2 is made on clinical features, the condition results from a change in the NF2 gene (mutation) that occurred for unknown reasons. This may occur either during the formation of the egg or sperm or during (or shortly after) conception. As in NF1, these are ‘spontaneous gene mutations’. The affected person is then the first person in a family to be affected with NF. That person will be able to pass on the faulty NF2 gene to their children but the chance of that may not always be 50 per cent.

If the mutation occurred shortly after conception of the baby, not all their cells may contain the mutation – the person is said to be ‘mosaic’ for the faulty NF2 gene. The faulty gene might not be in all their egg or sperm cells and so the chance that their child will inherit the faulty gene is less than 50 per cent.

People who are ‘mosaic’ for the NF2 faulty gene often have a milder form of the condition, and the tumours tend to occur on one side of the body (unilateral rather than bilateral). Nevertheless, if a child of a parent who is mosaic does inherit the faulty NF2 gene, the child will be more severely affected by the condition, as the faulty gene would be in all the cells of their body, unlike their parent. Also, that child has a 50 per cent risk of passing on the faulty gene to his or her children.

Pathology of NS2

The major feature of NF2 is the development of swellings (non-cancerous tumors) on the nerves that control hearing and balance (the auditory and vestibular nerves). The tumor that develops on the nerves is called a schwannoma. In the majority of cases, the schwannomas develop on both sides of the body (bilaterally) but not necessarily at the same time. This means the hearing loss may be of different degrees in both ears. In some cases, the schwannomas develop on only one side of the body (unilateral).

Diagnosis NF1 and NF2

Neurofibromatosis is diagnosed using a number of tests, including:

Advice on genetic testing

Children of a parent with NF2 should be considered to be at 50 per cent risk of having NF2. Screening for the tumors can start early in the child’s life. Genetic testing to determine if a person has definitely inherited the faulty NF2 gene requires the identification of the mutation in a family member who has NF2.

Once the mutation is identified, family members who have a 50 per cent risk of having inherited the faulty gene running in the family, but who do not have any symptoms of the condition, can have ‘pre-symptomatic’ genetic testing.

Family members who have not inherited the NF2 faulty gene do not have to be screened for symptoms, as they will not develop the condition. However, the identification of the mutation is time consuming and expensive, and the mutation may not be found in the gene even if it is there. In most families with more than one affected member, the genetic test will consider ‘markers’ in the DNA that are close to the gene and the age of onset of symptoms in the family. This will predict the likelihood that the faulty gene has been inherited.