Juhi Ramchandani

Neurofibromatosis

Juhi Ramchandani

Scheible 1A

Neurofibromatosis is a genetic disorder of the nervous system (NINDS, 2007). There are a total of three different types of neurofibromatoses (NINDS, 2007). The most common form is neurofibromatosis type1 (NF1), while the somewhat rareis neurofibromatosis type 2 (NF2) and the rarest being schwannomatosis (NINDS, 2007). Basically, this genetic disorder causes tumors to grow around the nerve cells in the nervous system (NINDS, 2007). The tumors, called neurofibromas are made up of fibrous substances which cover up the nerve cells (NINDS, 2007). They generally tend to be non-cancerous, yet patients are at risk of getting other forms of cancerspertaining to the nervous system (NINDS, 2007). Generally this disorder results in abnormalities such as bone deformities and skin changes (NINDS, 2007).

Neurofibromatosis type 1 (NF1), affects 1 in every 3000 to 4000 Americans (NINDS, 2007). Patients tend to inherit NF1 from their parents, but there have been cases in which the patients have spontaneously developed it (NINDS, 2007). In fact, approximately 30 to 50 percent of all NF 1 cases are spontaneous (NINDS, 2007). The NF1 mutation is located on chromosome 17 and as a result, can be passed on to future generations (Encyclopedia of Children’s Health, 2006). Neurofibromatosistype1 is a progressive disorder, meaning that its symptoms worsen over time (Encyclopedia of Children’s Health, 2006). Once a person is diagnosed with NF1, they may experience numerous symptoms (NINDS, 2007). These are generally non-life-threatening and most people with this disorder tend to have a normal life expectancy (NINDS, 2007). Scores of people with NF1 have learning disabilities (Encyclopedia of Children’s Health, 2006). They may also have freckles in the groin or armpit area and can have two or more lisch nodules or iris hamartomas (growth on the iris of the eye) (Gale Encyclopedia of Neurological Disorders, 2007). Patients may also suffer from optic glioma, a tumor growth on the optic nerve (Gale Encyclopedia of Neurological Disorders, 2007). In addition, several individuals are known for having scoliosis (abnormal development of the spine), sphenoid (abnormal development of the temple), or even an abnormal development of the bone of the skull or the tibia (one of the long bones of the shin) (Gale Encyclopedia of Neurological Disorders, 2007). Another symptom would be six or more “café-au-lait” spots (light brown spots) on the skin (NINDS, 2007). In children, these spots tend to be five or more millimeters in diameter, while in teens and adults they can be fifteen or more millimeters(Gale Encyclopedia of Neurological Disorders, 2007). Individuals may also have two or more neurofibromas or one plexiform neurofibroma (involves many nerves) in addition to having poor balance, headaches, epileptic seizures, and facial pain or numbness caused by pressure from the tumors (Gale Encyclopedia of Neurological Disorders, 2007).

Another form neurofibromatosis is neurofibromatosis type 2 (NF2) (NINDS, 2007). This disorder is somewhat rare and is diagnosed in 10 percent of all NF cases (NINDS, 2007). The NF2 mutation is located on chromosome 22 and causes several tumors to grow on the spinal and cranial (head) nerves (NINDS, 2007), in the brain,and on the spinal cord in the central nervous system (see Figure 1.1 and Figure 1.2) (Gale Encyclopedia of Neurological Disorders, 2007). A few common traits found among NF2 patients were that they tended to have hearing and visual problems (Encyclopedia of Children’s Health, 2006). Patients suffering from NF2 may experience a ringing noise in the ear (tinnitus) and hearing loss as early as in their teens due to the presence of neurofibromas in both acoustic nerves (nerves responsible for enabling sound to travel to the brain) (NINDS, 2007). Additionally, patients suffering from this disorder may also experience headaches, pain, or facial (Gale Encyclopedia of Neurological Disorders, 2007). Some were known for possessing café-au-lait macules (a lot fewer than NF1) and cataracts (abnormal clouding of the lens of the eye) and having neurofibromas both under and on the skin, but considerably less than NF1 (NINDS, 2007). It can be diagnosed through the use of a Gadolinium-enhanced MRI (Encyclopedia of Children’s Health, 2006).

Moreover, the last and rarest form of neurofibromatosis would be schwannomatosis (NINDS, 2007). Only 15 percent of all cases are inherited, meaning that this disease generally occurs spontaneously (NINDS, 2007). Further bizarre is the fact that if schwannomatosis has afflicted a relative in the past, it tends to skip a couple of generations until it afflicts someone else (NINDS, 2007). The feature that distinguishes schwannomatosis would be the development of multiple schwannomas (tumors) everywhere in the body except on the vestibular nerve (NINDS, 2007). The common, most dominant symptom would be excruciatingly intense pain which develops due to the enlargement of a schwannoma (large tumors), which causes the compressing of nerves or pressing onto an adjacent tissue (NINDS, 2007). Almost a third of patients have these tumors limited to a specific part of their body, for instance on their leg, arm, or a segment of the spine (NINDS, 2007). Everyone experiences at the minimum some degree of pain, yet they may also suffer from some other symptoms, some of which include tingling, numbness, and weakness in the toes and fingers (NINDS, 2007). The causes of this disease and its many symptoms still remain a myth to researchers all over the world (NINDS, 2007).

There have been many significant milestones in neurofibromatosis history. The first known drawing of someone who possibly may have had NF1 dates to the 13th century (Korf, 2005). In 1785, a British physician named Mark Akenside published the first English-language description of a patient suffering from NF1 manifestations (Korf, 2005). In 1822, probably the first description of NF2 was made by J. H. Wishart, a Scottish physician (Korf, 2005). He described a patient with cranial tumors (including acoustic neuroma) and several intracranial meninglomas (Korf, 2005). In 1830, Schwann identified a myelin sheath cell, later known as the most common type of cell in tumors formed during neurofibromatosis, while in 1882, a German physician and pathologistnamed Friedrich Daniel von Recklinghausen published a breakthrough monogram about the disorder that would later take his name (Korf, 2005). After observing neurofibromatosis tumors and how they were comprised of fibrous supportive tissue and nerve cells, he coined the term “neurofibroma” (Korf, 2005). Furthermore, the National Institute of Health hosted a significant consensus development conference where they provided guidelines for the treatment of NF1 and NF2 and established the nomenclature “NF1” and “NF2” as the diagnostic criteria for the two disorders (Korf, 2005). Also in 1987 was the identification of the chromosomes where the genetic data of NF1 (chromosome 17) and NF2 (chromosome 22) was located (Korf, 2005). Two independent groups identify and describe the NF1 gene and protein in 1990, while scientists did the same about the NF2 gene and protein product in 1993 (Korf, 2005).

So far, doctors have not come up with a cure for this disorder, nor are they able to stop or prevent it in any way (Encyclopedia of Children’s Health, 2006). Their main goal is to control or relieve the symptoms, which tend to be treated individually generally through surgery (recommended) (Encyclopedia of Children’s Health, 2006). Through surgery, the doctors would remove the tumors and the NF1 bone malfunctions (Encyclopedia of Children’s Health, 2006). It is not always the best option for treating the disease since there are many complications and malfunctions, like tumors growing back (Encyclopedia of Children’s Health, 2006). Another form of treatment is medication (Encyclopedia of Children’s Health, 2006). Doctors can prescribe certain medications to relieve the patients of their symptoms, like headaches with epileptic seizures (Encyclopedia of Children’s Health, 2006). If the tumors are malignant, surgery may be used to remove the tumors completely, but this may result in hearing loss (Encyclopedia of Children’s Health, 2006). Radiation or chemotherapy may also be used to treat malignant tumors (Encyclopedia of Children’s Health, 2006).

Presently, research is being conducted as to finda treatment plan or cure that would make the patients live a normal, healthylife (Encyclopedia of Children’s Health, 2006). Scientists have found that Guanosine triphosphatase-activating proteins (GAP proteins) play an important role in tumor suppression in specific cancers and that they may be used to treat this disorder (Encyclopedia of Children’s Health, 2006). New inheritance cases may be prevented through careful genetic counseling (Encyclopedia of Children’s Health, 2006). Certain clinical trials are being conducted to see how to treat the disease (Encyclopedia of Children’s Health, 2006). Drugs like R115777, pirfenidone, tipifarnib, and a combination of Methotrexate or vinblastine therapy are being studied (Encyclopedia of Children’s Health, 2006). Research is being conducted using MRI (shows brain structure), neuropsychological tests (measures certain cognitive skills), and functional MRI (shows area of brain at work) to find a connection between brain abnormalities and certain cognitive disabilities (NINDS, 2007). In addition, scientists identified two different patterns of clinical features in patients with NF2 (Encyclopedia of Children’s Health, 2006). These patterns are continuously being studied to see whether or not if they correspond to specific types of gene mutation (Encyclopedia of Children’s Health, 2006).

There have been numerous cases throughout the world in which people have developed this tumor-forming genetic disorder, thus making neurofibromatosis quite common (NINDS, 2007). It occurs equally in both sexes and in all races and ethnicities around the world (Encyclopedia of Children’s Health, 2006). Roughly 100,000 Americans are afflicted with this disorder (NINDS, 2007). So far, doctors have been unable to come up with a probable cure, but hopefully the future will hold new technology and innovative figures that may be able to battle this disease and save thousands of lives (NINDS, 2007).

References

Korf, Bruce R. and Rubenstein, Allen E. (2005). Neurofibromatosis: A Handbook for

Patients, Families, and Health Care Professionals. New York, NY: Thieme Medical Publishers.

Neurofibromatosis. Encyclopedia of Children’s Health. Retrieved December 07, 2007 from

Answers.com Web site:

Neurofibromatosis. Gale Encyclopedia of Neurological Disorders. Retrieved November 25,

2007, from Answers.com Web site:

Neurofibromatosis. Gale Encyclopedia of Neurological Disorders. Retrieved December 07,

2007, from Answers.com Web site:

Rogers, S. D. (2007). Neurofibromatosis. Grolier Multimedia Encyclopedia. Retrieved

December 7, 2007, from Grolier Online

(2007, November 19). NINDS Neurofibromatosis Information Page. Retrieved November 25,

2007, from National Institute of Neurological Disorders and Stroke Web site:

(2007, December 13). NINDS Neurofibromatosis Information Page. Retrieved December 27,

2007, from National Institute of Neurological Disorders and Stroke Web site:

Figure 1.1:

Figure 1.2: