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ODHHS Information
Neurofibrimatosis and Hearing Loss
(Source: Boystown Research Registry)  
Neurofibromatosis is a name given to a group of conditions that have several characteristics in common. "Neuro" refers to nerves, and "fibromatosis" refers to a growth that is fiber-like inside. Thus, a common characteristic of the neurofibromatosis disorders is the growth of round fibrous lumps along the nerves. These tumors are rarely cancerous, but can cause problems if they push on the nerves or other parts of the body or if they are visible on the skin. Another characteristic of the neurofibromatosis disorders is cafe au lait (kaffay-oh-lay) spots, which are light brown spots on the skin. They get their name from the color, which is similar to "coffee with cream". The different forms of neurofibromatosis have different characteristics, and different risks for hearing loss.
All types of Neurofibromatosis are caused by an autosomal dominant gene. Since all genes come in pairs, a person with neurofibromatosis would have one gene for neurofibromatosis and one "normal" gene, and each of their children would have a 50-50 chance of inheriting the neurofibromatosis gene. At least 9 different forms of neurofibromatosis have been described (1, 2). Some of these may be caused by different genes, but some of these may actually be different forms of the same gene. However, we do know that at least two forms of neurofibromatosis are genetically separate, because they are caused by genes on different chromosomes. These have been called Neurofibromatosis Type I (NFI) and Neurofibromatosis Type II (NFII).

Neurofibromatosis Type I has also been called Von Recklinghausen´s Disease (VRNF) or Peripheral Neurofibromatosis. It used to be said that John Merrick, "The Elephant Man", had VRNF, but now it is felt that he had a different condition called Proteus syndrome, which explains why his condition was so much more severe than is usually seen with NFI.
NFI is the most common type of NF. About one in every 3,000 newborns have NFI, and it accounts for 90% of the people with Neurofibromatosis. In about half of the cases of NFI, the person with NFI is the only one in their family with the gene; in other words, a normal gene changed ("mutated") to produce an NFI gene. Genes often change, but usually they are harmless changes that we never notice. Occasionally, however, a change in a gene will produce a disease, and for some reason the "normal" gene is particularly susceptible to changes which produce an NFI gene.
This fact sheet does not go into a complete description of all of the characteristics of NFI, but will briefly review the major findings to give an impression of the condition. We recommend that you talk to your doctor and consult the references at the end of this sheet if you want more information.
Genetic tests are being developed to diagnose NFI, but at this time, the diagnosis depends on a group of symptoms. This can be difficult because in NFI, there are a number of different signs, and a person with the gene may only have a few of the signs. Also, the signs of NFI develop with time. To help solve these problems, a committee was set up by the National Institutes of Health (NIH) to decide on the criteria that all doctors should use to diagnose NFI(3).
Usually the first signs of NFI are the cafe au lait spots. These spots are fairly common in all people, but people with NFI have more of them, so the number and size are important in making the diagnosis. There must be more than 6 spots, and in children before puberty, the spots must be larger than 5mm (about 1/4 inch). After puberty the spots must be larger than 15mm. Neurofibromas can be quite numerous and can occur anywhere, but are common in the skin of the face and trunk. They tend to appear around puberty. They can be removed surgically, but may grow back. Axillary freckling is another common finding and refers to freckles in the armpits; not a serious problem, but quite characteristic for NFI! Lisch nodules are tiny bumps on the iris of the eye which are very common in NFI. Usually an eye doctor needs to do a particular examination to see them. Optic gliomas are growths along the optic nerve that goes from the eye to the brain. These may eventually cause vision problems, so if they are present, a doctor needs to monitor them to see if they grow. Some people with NFI also have problems with the shape of their bones. Scoliosis, or curvature of the spine, is a common complication of NFI. Other types of tumors may also occur.
Hearing loss can occur in NFI, but is not common, and deafness is rare. A sensorineural loss may be due to a structural problem in the inner ear, or a neurofibroma may actually block the outer or middle ear resulting in a conductive loss. These types of losses are different than the loss due to acoustic neuromas (tumors of the auditory nerve) in NFII. It has also been noted that children with NFI have an abnormality in the way their brains receive nerve impulses from the ears, but at this time there is no proof that this causes hearing problems.
Although there are many possible complications of NFI, and people especially fear the disfiguring neurofibromas, it is important to realize that 2/3 of the people with NF do not have any serious complications. There are excellent support organizations for people with NF, where they can get more information about the condition and keep up with the latest in research. Information about support groups is provided at the end of this fact sheet.
The gene for NFI has been found to be on chromosome 17, and now the gene itself has been identified. Hopefully, this will eventually lead to a cure. The localization of the gene means that early diagnosis is also possible in some cases. The gene is large and there are many different mutations or changes in the gene that produce the same disease Each family will need to be studied to determine which type of gene mutation they have in order to tell if someone in that family has the gene. Alternatively, linked markers (that is, genes that are very close to the NFI gene on chromosome 17) can be used to tell if someone in the family inherited the chromosome with the NF gene. When no one else in the family has NFI, the diagnosis would be more difficult. If NFI is suspected in a child, it may be necessary to screen for a number of possible gene mutations until the right one is found; a negative answer could either mean the child does not have NFI, or the mutation was not found.

Neurofibromatosis Type II has also been called Central Neurofibromatosis or Bilateral Acoustic Neurofibromas (BANF). This form is much less common than NFI, and the gene is thought to be present in 1 in every 50,000 newborns. The primary feature is the presence of acoustic neuromas, which are tumors which grow on the nerve that carries the sound information from the cochlea to the brain. (This nerve is called the auditory and vestibular nerve complex, or cranial nerve VIII). Through pressure on the nerve, the tumor can gradually produce deafness. In at least 90% of the cases of NFII, the neuromas are bilateral, that is, the nerves from both ears are involved.
As with NFI, diagnostic criteria have been set out by the NIH Consensus Committee (3). Cafe au lait spots also occur in NFII, and there may be some neurofibromas of the skin, although these findings are less common than in NFI. Other tumors of the brain and spinal cord are more common in NFII, although optic gliomas are not usually found. A common early sign of NFII is a particular type of cataract, called a subcapsular cataract. NFII usually isn´t diagnosed until hearing loss is noticed, generally in the teens, but it can be earlier or later.
Problems in understanding speech may be noticed before the hearing loss is apparent, and tinnitus (ringing in the ears) may be present. Depending upon the size and location of the neuroma, the facial nerve and the vestibular system may also be affected, leading to paralysis of part of the face and balance problems. The hearing loss is progressive, and may produce complete deafness. Surgery to remove the tumors can be difficult, and some may not be totally removable. Early diagnosis is important, since smaller tumors may be easier to remove and hearing may be preserved. Also, if the diagnosis is made, examination can be done to be sure that there are not other tumors in other parts of the body.
The gene for NFII has been found to be on chromosome 22. Mutation in a tumor suppressor gene on chromosome 22 has been linked to NFII. It is now possible to identify within affected families those who are carriers and those who are not carriers of the gene. In those who carry the NFII mutation, the tumors are caused by the loss of the normal gene on the other chromosome in the affected tissue. Hopefully, this discovery will lead us to a means of preventing tumor growth for those who are carriers.

Comparison of some of the features of NFI and NFII
Clinical features           NFI  NFII--------------------------------------cafe au lait spots          ++   -cutaneous neurofibromas     ++   +skeletal problems           +    -lisch nodules               +    -optic glioma                +    -axillary freckling          +    -subcapsular cataracts       -    +acoustic neuroma        unilateral          -    +        bilateral           -    ++--------------------------------------  + = present, ++ = very common, - = rare

Selected References
1. Riccardi, V.M., Eichner, J.E. (1986). Neurofibromatosis: Phenotype, Natural History, and Pathogenesis. Baltimore: The Johns Hopkins Univ. Press.
2. Gorlin, R.J., Cohen, M.M., Levin, L.S. (1990). Syndromes of the Head and Neck: Third Edition. New York: Oxford University Press.
3. National Institutes of Health Consensus Development Conference (1988). Neurofibromatosis Conference Statement. Arch. Neurology 45: 575-578.
4. Kitamura K., Senba, T., Komatsuzaki, A. (1989). Bilateral internal auditory canal enlargement without acoustic nerve tumor in von Recklinghausen neurofibromatosis. Neurofibromatosis 2: 47-52.
5. Pensak, M.L., et al., (1989). Neuroaudiologic abnormalities in patients with Type 1 Neurofibromatosis. Laryngoscope 99:702-706.
6. Xu, G., et al., (1990). The neurofibromatosis type 1 gene encodes a protein related to GAP. Cell 62: 599-608.
7. Sainz.J., et al., (1994). Mutations of the neurofibromatosis type 2 gene and lack of the gene product in vestibular schwannomas. Human Molecular Genetics 3: 885-891.

Support Groups
National Neurofibromatosis Foundation, INC.
141 Fifth Ave, Suite 7-S
New York, NY 10010
(800) 323-7938, TDD & V (212) 460-8980
25 chapters
Neurofibromatosis, Inc.
8855 Annapolis Rd, Suite 110
Lanham, MD 20706-2924
(800) 942-6825, TDD (410) 461-5213, V (301) 577-0016
10 chapters

Date Originally Created: Winter of 1990.
The information presented here first appeared in publications of the Boys Town National Research Register for Hereditary Hearing Loss, the National Institute on Deafness and Other Communication Disorders (NIDCD), Hereditary Hearing Impairment Resource Registry (HHIRR), or the Boys Town Research Registry for Hereditary Hearing Loss.
The Boys Town Research Registry for Hereditary Hearing Loss
The Boys Town Research Registry for Hereditary Hearing Loss (Registry) is designed to foster a partnership between families, clinicians and researchers in the area of hereditary hearing loss/deafness through three primary functions. First, the Registry disseminates information to professionals and families about clinical and research issues related to hereditary deafness/hearing loss. Second, the Registry collects information from individuals interested in supporting and participating in research projects. This information is used to support the third function of the Registry - matching families with collaborating research projects.
For more information, contact:
Research Registry for Hereditary Hearing Loss
555 N. 30th Street
Omaha, NE 68131
800 320-1171 (V/TDD)
402 498-6331 (FAX)