Neurofibromatosis
- What is Neurofibromatosis?
- Is there any treatment?
- What is the prognosis?
- What research is being done?
The neurofibromatoses are genetic disorders of the nervous system that primarily affect the development and growth of neural (nerve) cell tissues. These genetic disorders cause tumors to grow on nerves and produce other abnormalities such as skin changes and bone deformities. Although many affected persons inherit the neurofibromatosis disorder, between 30 and 50 percent of new cases arise spontaneously through mutation (change) in an individual's genes. Once this change has taken place, the mutant gene can be passed on to succeeding generations. Scientists have classified the disorders as neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2). NF1 is the more common type of the neurofibromatoses. In diagnosing NF1, a physician looks for changes in skin appearance, tumors, or bone abnormalities, and/or a parent, sibling, or child with NF1. Cause of neurofibromatosis, particularly those on the skin, are often evident at birth or during infancy and almost always by the time a child is about 10 years old. NF2 is less common. NF2 is characterized by bilateral (occurring on both sides of the body) tumors on the eighth cranial nerve. The tumors cause pressure damage to neighboring nerves. To determine whether an individual has neurofibromatosis disease, a physician looks for bilateral eighth nerve tumors and similar signs and symptoms in a parent, sibling, or child. Affected individuals may notice hearing loss as early as the teen years. Other early neurofibromatosis symptoms may include tinnitus (ringing noise in the ear) and poor balance. Headache, facial pain, or facial numbness, caused by pressure from the tumors, may also occur.
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What are the signs and symptoms of NF1?
To diagnose neurofibromatosis 1, a doctor looks for two or more of the following:
- Six or more light brown spots on the skin (often called “cafe-au-lait” spots), measuring more than 5 millimeters in diameter in children, or more than 15 millimeters across in adolescents and adults;
- Two or more neurofibromas, or one plexiform neurofibroma (a neurofibroma that involves many nerves);
- Freckling in the area of the armpit or the groin;
- Two or more growths on the iris of the eye (known as Lisch nodules or iris hamartomas);
- A tumor on the optic nerve (optic glioma);
- Abnormal development of the spine (scoliosis), the temple (sphenoid) bone of the skull, or the tibia (one of the long bones of the shin);
- A first degree relative (parent, sibling, or child) with neurofibromatosis type 1.
Many children with neurofibromatosis 1 have larger than normal head circumference and are shorter than average. Hydrocephalus, the abnormal buildup of fluid in the brain, is a possible complication of the disorder. Headache and epilepsy are also more likely in individuals with NF1 than in the normal population. Cardiovascular complications are associated with neurofibromatosis type 1, including congenital heart defects, high blood pressure (hypertension), and constricted, blocked, or damaged blood vessels (vasculopathy) being effects of neurofibromatosis. Children with NF1 may have poor linguistic and visual-spatial skills, and perform less well on academic achievement tests, including those that measure reading, spelling, and math skills. Learning disabilities, such as attention deficit hyperactivity disorder (ADHD), are common in children with neurofibromatosis 1.
How is neurofibromatosis type 1 treated?
Since doctors don’t know how to prevent or stop neurofibromas from growing, surgery is often recommended to remove them. Several surgical options exist, but there is no general agreement among doctors about when surgery should be performed or which surgical option is best. Individuals considering surgery should carefully weigh the risks and benefits of all their options to determine which surgical treatment is right for them. There are also surgical and chemical techniques that can reduce the size of eye tumors (optic gliomas) when vision is threatened. In addition, some bone malformations, such as scoliosis, can be surgically corrected. In the rare instances when tumors become cause of neurofibromatosis that is malignant (3 to 5 percent of all cases), treatment may include surgery, radiation, or chemotherapy.
Neurofibromatosis disease treatments for other conditions associated with neurofibromatosis type 1 are aimed at controlling or relieving symptoms. Effects of neurofibromatosis like headache and epileptic seizures are treated with medications. Since there is a higher than average risk for learning disabilities, children with neurofibromatosis type 1 should undergo a detailed neurological exam before they enter school. Once these children enter school, if teachers or parents suspect there is evidence of a learning disability (or disabilities), they should request an evaluation that includes an IQ test and the standard range of tests to evaluate verbal and spatial skills. Children with learning disabilities are eligible for special education services under the provisions of the Individuals with Disabilities Education Act (IDEA).
What are the signs and symptoms of NF2?
To diagnose neurofibromatosis 2, a doctor looks for the following:
- Bilateral vestibular schwannomas, or
- A family history of NF2 (parent, sibling, or child) plus a unilateral vestibular schwannoma before age 30
- Glioma,
- Meningioma,
- Schwannoma,
- Juvenile posterior subcapsular lenticular opacity (juvenile cortical cataract).
Neurofibromatosis 2 is best managed at a specialty clinic with an initial screening and annual follow-up evaluations. Improved diagnostic technologies, such as MRI (magnetic resonance imaging), can reveal tumors as small as a few millimeters in diameter, which allows for early treatment. Vestibular schwannomas grow slowly, but they can grow large enough to completely engulf the eighth cranial nerve. Early surgery, to completely remove the tumor while it’s still small, might be advisable to preserve hearing and balance. There are several surgical options, depending on tumor size and the extent of hearing loss. Some techniques preserve the auditory nerve and enable individuals to retain some hearing; other techniques may involve removing the nerve and replacing it with an electronic auditory implant in the brainstem to restore hearing. Surgery is available to correct cataracts and retinal abnormalities. A strategy of watchful waiting might be more appropriate for slowly growing brain and spinal tumors, which have higher risks of surgical complications.
Is there any treatment?
Treatments for both neurofibromatosis 1 and neurofibromatosis 2 are presently aimed at controlling symptoms. Surgery can help some NF1 bone malformations and remove painful or disfiguring tumors; however, there is a chance that the tumors may grow back and in greater numbers. In the rare instances when tumors become malignant (3 to 5 percent of all cases), neurofibromatosis disease treatment may include surgery, radiation, or chemotherapy. For NF2, improved diagnostic technologies, such as MRI, can reveal tumors as small as a few millimeters in diameter, thus allowing early treatment. Surgery to remove tumors completely is one option but may result in hearing loss. Other options include partial removal of tumors, radiation, and if the tumors are not progressing rapidly, the conservative approach of watchful waiting. Genetic testing is available for families with documented cases of NF1 and NF2. New (spontaneous) mutations cannot be confirmed genetically. Prenatal diagnosis of familial neurofibromatosis disease is also possible utilizing amniocentesis or chorionic villus sampling procedures.
What is the prognosis?
In most cases, symptoms of neurofibromatosis 1 are mild, and patients live normal and productive lives. In some cases, however, NF1 can be severely debilitating. In some cases of neurofibromatosis 2, the damage to nearby vital structures, such as other cranial nerves and the brainstem, can be life-threatening.
What research is being done?
Several years ago, research teams located the exact position of the NF1 gene on chromosome 17. The product of the NF1 gene is a large and complex protein called neurofibromin. One portion of this protein is similar to a family of proteins called GAP (guanosine triphosphatase-activating protein). Scientists have demonstrated that GAP proteins play a significant role in tumor suppression in certain cancers. The similarity of the NF1 protein to GAP proteins suggests that the neurofibromatosis 1 protein may have a similar switching role in the cause of neurofibromatosis. Scientists theorize that defects in the gene may lessen or inhibit the normal output of its protein and allow the irregular cell growth that may lead to tumor development. Intensive efforts have led to the identification of the NF2 gene on chromosome 22. The neurofibromatosis 2 gene product is a tumor suppressor protein. Basic studies in molecular genetics may lead one day to nonsurgical or pharmacologic treatments aimed at retarding or suppressing tumors associated with the neurofibromatoses. The Interinstitute Medical Genetics Research Program at the NIH Clinical Center conducts NF2 family history research. Using specimens from some of the families, scientists have isolated and sequenced the NF2 gene and have described two different patterns of clinical features in NF2 patients. Investigators are continuing to study these patterns to see if they correspond to specific types of gene mutations.
Information Obtained From National Institute Of Health