Neurofibromatosis

Definition

Neurofibromatosis (NF), or von Recklinghausen disease, is a disorder that causes development of multiple soft tumors (neurofibromas). These tumors occur under the skin and throughout the nervous system (cells which control body movement and sensation).

Description

Neural crest cells are primitive cells that exist during fetal development. These cells eventually turn into cells that form nerves throughout the brain, spinal cord, and body. Collectively, this system of nerve cells is called the nervous system, which coordinates movement and sensation. Some nerve cells carry impulses from the brain to muscles or other peripheral structures, hence the name peripheral nervous system. Another group of nerve cells called the central nervous system are capable of transmitting sensation back to the brain for interpretation (such as feeling cold or hot).

In neurofibromatosis, a genetic defect causes these neural crest cells to develop abnormally. This results in numerous tumors and malformations of the nerves, bones, and skin.

Genetic profile

A defective gene causes both forms of neurofibromatosis. NF-1 is due to a defect on chromosome 17; NF-2 results from a defect on chromosome 22. Both of these disorders are inherited as a dominant trait. This means that anybody who receives just one defective gene will have the disease. However, a family pattern of NF is only evident for about half of all cases of NF. The other cases of NF occur due to a spontaneous mutation (a spontaneous and permanent change in the structure of a specific gene). Once a spontaneous mutation has been established in an individual it is then possible to be passed on to any offspring. The chance of a person with NF passing on the NF gene to their child is 50%. There are different pathologic alleles (variations of the mutant gene). The frequency of spontaneous (new) mutations is very high and causes for this are still unknown.

Demographics

Neurofibromatosis-I occurs in about one of every 4,000 births. Neurofibromatosis-I is one of the most common genetic disorders that is dominantly inherited. Two types of NF exist, NF-1 (90% of all cases), and NF-2 (10% of all cases).

Signs and symptoms

NF-1 has a number of possible signs and can be diagnosed if any two of the following are present:

• The presence of café-au-lait (French for coffee-with-milk) spots. These are patches of tan or light brown skin, usually about five to 15 mm in diameter. Nearly all patients with NF-1 will display these spots.

• Multiple freckles in the armpit or groin area.

• Ninety percent of patients with NF-1 have tiny tumors called Lisch nodules in the iris (colored area) of the eye.

• Neurofibromas. These soft tumors are the hallmark of NF-1. They occur under the skin, often located along nerves or within the gastrointestinal tract. Neurofibromas are small and rubbery, and the skin overlying them may be somewhat purple in color.

• Skeletal deformities, such as a twisted spine (scoliosis), curved spine (humpback), or bowed legs.

• Tumors along the optic nerve (the nerve cells which transmit a visual stimulus to the back part of the brain called the occipital lobe, for interpretation), which cause vision disturbance occurs in about 20% of patients.

• The presence of NF-1 in a patient's parent, child, or sibling.

• Hypertension or elevated blood pressure.

There are very high rates of speech impairment, learning disabilities, and attention deficit disorder in children with NF-1. Other complications include the development of a seizure disorder (an abnormal firing of nerve cells in muscles, causing severe contractions, sometimes involving the whole body), or abnormal accumulation of fluid within the brain (a condition called hydrocephalus). A number of cancers are more common in patients with NF-1. These include a variety of types of malignant brain tumors, as well as leukemia, and cancerous tumors of certain muscles the adrenal glands or the kidneys (Wilms' tumor).

Patients with NF-2 do not necessarily have the same characteristic skin symptoms (café-au-lait spots, freckling, and neurofibromas of the skin) that appear in NF-1. The characteristic symptoms of NF-2 are due to tumors along the acoustic nerve. Interfering with the function of this nerve results in the loss of hearing; and the tumor may spread to neighboring nervous system structures, causing weakness of the muscles of the face, headache, dizziness, poor balance, and uncoordinated walking. Cloudy areas on the lens of the eye (called cataracts) frequently develop at an unusually early age. As in NF-1, the chance of brain tumors developing is unusually high.

Diagnosis

Diagnosis is based on the broad spectrum of clinical signs previously described, which usually can be detected by careful physical examination, ophthalmologic evaluation (visualizing the structures in the eye) and audiogram (test to measure hearing ability). Diagnosis of NF-1 requires that at least two of the listed signs are present. Diagnosis of NF-2 requires the presence of either a mass on the acoustic nerve or another distinctive nervous system tumor. An important diagnostic clue for either NF-1 or NF-2 is the presence of the disorder in a patient's parent, child, or sibling. A test to detect a protein (the end-products of a gene) relevant to NF-1 mutagenesis has been created, but accuracy for this procedure has not been established.

Monitoring the progression of neurofibromatosis involves careful testing of vision and hearing. X ray studies of the bones are frequently indicated to detect for the development of deformities. CT scans and MRI scans are performed to track the development/progression of tumors in the brain and along the nerves. Auditory evoked potentials (the electric response evoked in the cerebral cortex by stimulation of the acoustic nerve) may be helpful to determine acoustic nerve involvement, and EEG (electroencephalogram, a record of electrical impulses in the brain) may be required for patients with suspected seizures. Regular blood pressure monitoring is also advised.

Treatment

There are no available treatments for the disorders that underlie either type of neurofibromatosis.

Prognosis

Prognosis varies depending on the tumor type, which develops. As tumors grow, they begin to destroy surrounding nerves and structures. Ultimately, this destruction can result in blindness, deafness, increasingly poor balance, and increasing difficulty with the coordination necessary for walking. Deformities of the bones and spine can also interfere with walking and movement. When cancers develop, prognosis worsens according to the specific type of cancer.

Prevention

There is no known way to prevent the approximately 50% of all NF cases that occur due to a spontaneous change in the genes (mutation). New cases of inherited NF can be prevented with careful genetic counseling. A person with NF can be made to understand that each of his or her offspring has a 50% chance of also having NF when a parent has NF. Special tests can be performed on the fetus (developing baby) during pregnancy to determine if the fetus will be born with this disorder.

THIS IS GENERAL INFORMATION ON DISEASE. PLEASE CONTACT YOUR DOCTOR FOR MORE DETAILS AND TREATMENT.

Compiled by –Santosh  Ghodinde ,Community Pharmacist, Dhanwantari Medical, Panvel.