Getting to know Neurofibomatosis

Neurofibromatosis can affect the body in many ways, and it can affect different people in very different ways. In some it may be nothing more than a nuisance, but in others it can cause important medical problems. It is natural to have lots of questions when a person is told that he or she has a condition such as neurofibromatosis. How will this affect my health? Will it change my appearance? Why did it happen? What can be done about it? What should I tell my friends? Can I pass it on to my children? These are important questions; anyone affected with neurofibromatosis should have the facts about the condition. This brochure has been written to explain what is known about neurofibromatosis, and what can be done to help deal with it.

Neurofibromatosis (commonly abbreviated NF) is a genetically-inherited disorder in which the nerve tissue grows tumors (neurofibromas) that may be benign or may cause serious damage by compressing nerves and other tissues. This disease affects male and female equally. This kind of disorder is resulted by gene mutation and affects all neural crest cells in our body such as Schwann cells, melanocytes and endoneurial fibroblasts. Cellular elements from these cell types proliferate excessively throughout the body, forming tumors; melanocytes also function abnormally in this disease, resulting in disordered skin pigmentation. The tumors may cause bumps under the skin, colored spots, skeletal problems, pressure on spinal nerve roots, and other neurological problems.

Neurofibromatosis is an autosomal dominant disorder, which means this kind of disease can develop starting with only one copy of the affected gene. If both parents has this disease the children will have this disease for sure and when only one parent has it, the child will have a 50% of chance in getting this disease.

Neurofibromatosis is considered as a member of the Neurocutaneous syndrome.

Classifications

            This disorder is divided into three categories, NF 1, NF 2, Schwanommatosis; based on the different types of gene mutation, and the type of protein that is missing. NF 1 is caused by gene mutation on chromosome 17. It causes the lack of the Neurofibromin protein. NF2 is caused by gene mutation on chromosome 22. It causes the lack of the Merlin protein. Schwanommatosis is caused by gene mutation on chromosome 22 as well, but the missing protein is different from NF2. The missing protein is called SMARCB1.

Types of Disease	Protein missing
NF1	Neurofibromin (a regulator of the GTPase activating enzyme (GAP))
NF2	Merlin (cytoskeletal protein)
Schwanommatosis	SMARCB1

All three types of NF can cause several types of tumors to grow.

Including:

Gliomas - Tumors made of glial cells.

Meningiomas - Tumors arising from cells of the meninges (the protective layer surrounding the brain and spinal cord)

Schwannomas - tumors made of schwann cells, arising from the myelin sheath that protects our nerves.

Each type of tumors have different characteristics, growth rate and reaction to every treatment methods.

That's why it is VERY important to study and understand the natural history of Neurofibromatosis when treating a patient with this genetic disorder, because using the wrong type of surgical approach for the wrong type of tumor can cause detrimental and irreversible effects on the patient.

I would emphasize this: NF patients who are treated by doctors familiar with this conditon, whose condition is carefully monitored and planned in the long-term, can live full and active lives. In more developed countries like the U.S. patients can live active and high achieving lives despite battling Neurofibromatosis. Some NF patients in the U.S. even run marathons and climb Mount Kilimanjaro to raise awareness for this genetic disorder. On the other hand, other patients who were treated by doctors that lack the experience or knowledge in the treatment of NF can become paralyzed and even lose their life after one or two surgeries.

Many would emphasize on how tragic and devastating this condition is, to get a reaction from their readers or listeners. But I personally prefer to emphasize that what we really need is for doctors to treat us carefully. Plan our treatments carefully and not remove our tumors forcibly just because the tumors exist. Not every tumor that exist has to be removed. If the risk of removing a tumor far outweighs the benefit of removing it, the doctor should consider alternative treatment methods.

More often than not, patients fail to do their own research and understand about a particular tumor or their options, and blindly agree to their doctor's decision to operate on a tumor. This is very common in less developed countries, even in Malaysia. So my other emphasis would be to encourage the public to understand their health and condition, and not to simply rely on their doctors.

Signs and symptoms:

Patients with neurofibromatosis can be affected in many different ways. Morbidity is often a result of plexiform neuromas, optic gliomas, or acoustic neuromas, but mortality can also be associated with malignant transformation of the neuromas, such as neurofibrosarcomas (often there is a malignant transformation in less than 3% of the cases of NF1). Neurofibromatosis also increases the risk of leukemia particularly in children; Children with NF-1 have 200 to 500 times the normal risk of developing leukemia compared to the general population. Since the tumors grow where there are nerves, they can also grow in areas that are visible, causing considerable social suffering for those affected. The tumors can also grow in places that can cause other medical issues that may require them to be removed for the patient's safety. Affected individuals may need multiple surgeries (such as reduction surgery, or Gamma knife surgery), depending on where the tumors are located. For instance, those affected with NF 2 might benefit from a surgical decompression of the vestibular tumors to prevent deafness.

Diagnostic Features of Neurofibromatosis

There is no medical test available to definitively diagnose neurofibromatosis. The only way to tell that a person is affected is to examine him or her to see if there are signs of the disorder. There are several features that your doctor will look for, and it is generally agreed that anyone having at least two of the features on this list has NF1.

• 6 or more cafe-au-lait spots ( Brown patches)
• freckling under the arms or in the groin
• 2 or more neurofibromas
• Lisch nodules (tiny, tan bumps) on the iris of the eye • optic nerve tumor (optic glioma)
• characteristic bone abnormality
• family history of NF1

Diagnosis:

Prenatal testing:

Embryo: For embryos produced by in vitro fertilization it is possible via pre-implantation genetic diagnosis (PGD) to screen for NF-1. PGD has about 95-98% accuracy but requires that the partner with NF2 have a recognizable genetic mutation, which is only the case for about 60% of people with a clinical diagnosis of NF2. PGD cannot be used to detect Schwannomatosis‎, because the gene for it has not yet been identified.

Fetus: Chorionic villus sampling or amniocentesis can be used:

• To detect Neurofibromatosis type I‎.
• To detect Neurofibromatosis type II‎ with 95% accuracy.
• Cannot be used to detect Schwannomatosis‎, because the gene for it has not yet been identified.

Treatment:

There is no cure for the condition itself, the only therapy for patients with neurofibromatosis is a program of treatment by a team of specialists to manage symptoms or complications. Surgery may be needed when the tumors compress organs or other structures. Less than 10% of people with neurofibromatosis develop cancerous growths; in these cases, chemotherapy may be successful. Genetic screening and counseling is available for family with NF.