Neurofibromatosis By: Gurneet Bhela

Neurofibromatosis (NF)

____________________________________

BY: Gurneet Bhela

Neurofibromatosis is autosomal dominant genetic disorder that affects the nervous system also including the brain, spinal cord, nerves, skin, and other body systems in the body. People affected by this disorder develop non-cancerous tumours along their nerves, nerve tissue and under the skin. The non-cancerous tumours formed are called neurofibromas which disturb cell growth within the nervous system. There are two types of Neurofibromatosis- NF1 and NF2. The severity of both types of neurofibromatosis varies greatly. NF1 is more common and the chromosome that is affected is chromosome 17. NF-1 is caused by a mutation of a gene on the long arm of chromosome 17 which encodes a protein known as neurofibromin which plays an important role in cell signaling. For NF2 chromosome 22 is affected. NF2 is caused by mutations of the "Merlin" gene which influences the form and movement of cells.

Neurofibromatosis is an inherited disorder therefore an affected person has 1 chance in 2 of passing it on with each pregnancy but in some cases Neurofibromatosis can actually be the result of a spontaneous change (mutation) in the genetic material of the sperm or egg at conception even in families with no previous history of Neurofibromatosis.

A doctor who treats NF1, such as a neurologist, geneticist, dermatologist, or developmental pediatrician will diagnose this condition. NF1 is can sometimes be diagnosed in younger children who appear to have certain symptoms of spots on the skin that are at least ½ inch in size. But the spots are not enough for a complete diagnosis so when the grow continues to grow at the age of 10 Neurofibromas will begin to become evident on various parts of the body, beginning with the arms and then spreading to other parts.

For a child to be diagnosed with NF1 he/she must have at least two of the following symptons:

• café-au-lait spots of a certain number, size, and location
•  the appearance of two or more neurofibromas
•  an optic glioma (tumor along the main nerve of the eye that is responsible for sight)
•  certain skeletal abnormalities
•  a family member with NF1
• freckling under the arms or in the groin

café-au-lait spot

NF2 is usually not diagnosed until a child is older. Hearing loss in the late teens and early twenties is often among the first symptoms of the disorder, and is caused by tumors growing on the auditory nerves (which carry electrical impulses from the inner ear to the brain).

Tests like magnetic resonance imaging (MRI) and X-rays may be used to screen for tumors or evidence of skeletal problems. A child's head circumference will be measured because kids with symptoms of NF can have a circumference that's larger than normal for their age.

To diagnose NF2, doctors will check for any evidence of hearing loss. Audiometry (hearing tests) can be used as well as imaging tests to look for tumors in the nerves of the ears, spinal cord, or brain.

Genetic testing is available for people with a family history of either NF1 or NF2. Although testing is still not 100% sensitive, recent advances have increased sensitivity to over 90%. Prenatal testing may be used to identify the disorder of NF-1 in the fetus. Preimplantation genetic diagnosis and Chorionic villus sampling can be used to screen for Neurofibromatosis.

Preimplantation genetic diagnosis

NOTE: Preimplantation genetic diagnosis: a technique using in vitro fertilization to ensure that a baby does not possess a known genetic defect of either parent

Chorionic villus sampling: is a form of prenatal diagnosis to determine chromosomal or genetic disorders in the fetus

People diagnosed with Neurofibromatosis have a normal life span.  Neurofibromas on or under the skin can increase with age and cause cosmetic and psychological issues.

Once a person has developed Neurofibromatosis there is no cure that can completely reverse the genetic disorder. Instead the treatments for neurofibromatosis focus on controlling the existing symptoms. For a more complex case where the symptoms are high and dangerous, options for treatment are necessary. Surgery can be performed to remove problematic growths or tumors, chemotherapy or radiation if a tumor has turned malignant or cancerous, surgery for bone problems and therapy. These treatments can be used for both NF1 and NF2 depending on the individual’s progress. Although this treatment is not able to cure the disease, it is still possible to live a normal healthy life if the symptoms are regularly monitored and controlled so it is important to be diagnosed at an earlier age.

There are no ethical issues concerning the treatment of this disease but it is a rare genetic that deserves to raise awareness for. Recently, non-profit and charitable organizations have started to bring awareness and education about Neurofibromatoses to mainstream media in order to better connect those affected with helpful resources to lead more productive and satisfying lives.

In terms of further studies regarding Neurofibromatosis, there are many organizations who have the goal to help provide better therapies for affected patients, provide outstanding clinical care and also educating families about this genetic disorder. I believe Neurofibromatosis is a more complicated disease because it is concerned with the nervous system which makes it more difficult to study the body’s nerves. But the focus of study should be directed towards how this mutation occurs in the chromosomes and how it changes the genes of a person’s appearance very rapidly. There is a need to study the cause rather than the result; further studies need to be targeted to understand which changes in the NF1 gene that leads to various symptoms and associated features. The two chromosomes are connected to the function of the brain and nervous system so perhaps studying how brain productivity and function changes and to what scale compared to a healthy human body will be useful for finding a potential cure.

                                                           A question for thought:

Why do you think the symptoms for NF1 and NF2 are quite different from each other even though they are both a genetic disorder of Neurofibromatosis? If you were a scientist, doctor or researcher which type of Neurofibromatosis do you think would be more important to study further NF1 or NF2?

                                                      

References:

http://en.wikipedia.org/wiki/Neurofibromatosis_type_I

http://chealth.canoe.ca/condition_info_details.asp?disease_id=329

http://kidshealth.org/parent/general/aches/nf.html

http://www.webmd.com/pain-management/neurofibromatosis?page=2