The neurofibromatoses (NF) are genetic disorders of the nervous system. At this time two

distinct forms are known: NF1 and NF2. One baby in every four thousand is born in the

United States with NF1. It is one of the most common genetic disorders, affecting some

one hundred thousand americans. NF2 is less common and occurs in only one and every

forty thousand births. In both forms of NF severity of symptoms vary greatly.

The effects can be severely disabling, mildly disfiguring or can even go undetected.

Several other names for this disorder have been used in the past but recent advancements

in understanding the disorder made some of those terms obsolete.

NF1 was previously known as peripheral neurofibromatosis, or von Recklinghouasen’s

disease after the doctor who first described it in 1882. NF2 was called bilateral acoustic

nuerofibromatosis, central neurofibromatosis, or vestibular schwannoma.

NF is found in every racial and ethnic group throughout the world and

affects both sexes equally. Both neurofibromatosis1 and neurofibromitosis2 are caused

by abnormal genes. This disease cannot be "caught" from someone who has it already. .

A common early sign of NF1 is six or more tan spots on the skin. They are

called "cafe-au-lait" (French for "coffee with milk") spots. These spots are

often present at birth, and may increase in size and number with age. They

also may become darker. More than half of affected children have some signs

of NF1 by 2 years of age.

Benign tumors (lumps), under the skin or deeper, may appear at any age but

especially during adolescence. The tumors, which grow on nerves, are made

up of cells that surround nerves and other cell types, and are called

neurofibromas. An affected person may have any number of neurofibromas,

from none to hundreds. The tumors, which vary in size, may or may not be

painful. A person also may have a single neurofibroma without having NF.

Some tumors may grow on the optic (eye) nerves and in rare cases may

interfere with vision. Tiny tan or brown "Lisch nodules" (small tumors) often

appear on the iris (colored part of the eye), but these cause no trouble. They

usually show up around age 6 to 10 years and may help a doctor diagnose

NF1. NF2 is characterized by tumors that grow on what is referred to as the

8th cranial nerve (one of 12 pairs of nerves that enter or emerge from the brain). These

tumors often cause pressure on the acoustic (hearing) nerves, resulting in hearing loss.

Persons with NF2 also may develop other tumors of the brain or spinal cord, and

sometimes develop cataracts at an early age. Persons with NF2 have few, if any, cafe-au-

lait spots or tumors under the skin. Symptoms of NF2 may not begin until after puberty.

NF1 and NF2 are caused by two separate abnormal genes. The abnormal gene in each

form of NF can either be inherited from one parent who has the disorder or can result

from a new mutation (change) in the gene. Thus, NF can occur in a person who has no

family history of the condition. About 50 percent of NF1 and NF2 cases are caused by

new mutations. An individual with NF caused by a new mutation can have the same

variety of signs and symptoms as a person who inherited it from an affected parent.

Inheritance of the gene is "autosomal dominant", so that the child of a parent with NF has

a 50-50 chance of inheriting the NF gene and showing at least some signs of

neurofibromatosis sooner or later. The child also has a 50-50 chance of inheriting the NF

gene's normal partner (since genes come in pairs) and remaining free of NF.

In most cases of NF1, symptoms are mild and affected individuals live a normal life.

Some individuals have many skin neurofibromas (lumps on the nerves) on the face and

body. Neurofibromas also can grow inside the body. Neurofibromas may increase during

puberty and pregnancy because of hormonal changes. Scoliosis (a progressive curvature

of the spine) is common in NF and can begin at an early age.

Some children with NF1 have learning disabilities, speech problems and/or seizures, and

may be hyperactive. Some affected children and adults have large heads. This usually

does not reflect a serious medical problem. Eye tumors may cause bulging of the eye, or

visual difficulties. A variety of bone defects may be present at birth, including bowing of

the legs below the knee. Children with NF1 appear to be at increased risk of certain

cancers, though these are rare.

Symptoms of NF2 may include hearing loss, ringing in the ears, dizziness, balance

problems, headaches or seizures. Early removal of small auditory nerve tumors

sometimes helps to preserve hearing. A diagnostic technique called magnetic resonance

imaging has improved early diagnosis of tumors.

There is no way of predicting the degree of severity either form of NF will have.

As with many other genetic disorders, psychological problems may occur in NF patients.

Some become lonely and withdrawn because they feel "different" from others. They may

be concerned about whether or not to have children. They often are worried about further

complications.

There is no cure for NF, but there are ways to treat some of its effects. Painful or

disfiguring skin tumors can be removed by surgery. However, they may grow back.

Tumors on the eye or ear nerves sometimes can be removed or treated with radiation or

chemotherapy. Scoliosis may be treated by surgery, a brace, or both.

There are a number of multidisciplinary NF clinics throughout the United States that

address specific medical concerns and routine NF-related health care issues of

individuals and families affected by NF.

Recent research advances may lead to improved treatments for NF1 and NF2.

Researchers have found the gene for NF1 on the 17th chromosome, and the gene for NF2

on the 22nd chromosome. Scientists are using this information to develop precise tests

aimed at definitively diagnosing these disorders, even before an individual develops

symptoms. Early diagnosis should allow doctors to treat symptoms sooner, possibly

preventing some serious complications. Researchers also have identified the protein

products these genes dictate, and are beginning to understand the functions of these

proteins. This may lead to the development of drugs to treat some of the symptoms of

these disorders.

In rare instances, cases of NF occur that are not consistent with NF1 or NF2, or have

features of both. Very little is known about these rare conditions.

NF1 and NF2 usually can be diagnosed on the basis of signs and symptoms alone.

However, genetic testing is available and can be used in some cases for prenatal

diagnosis and to help evaluate individuals with a family history of these disorders who do

not yet show symptoms.

There are two major types of genetic testing. The first is called linkage analysis, and is

used for families in which there are more than two affected members. Linkage analysis

requires blood tests on multiple family members, and it tracks the chromosome that

harbors the disease-causing gene through two or more generations. In general, linkage

testing is more than 95 percent accurate in predicting whether or not an individual has

NF. The second test, direct gene mutation analysis, does not require the testing of other

family members. However, it is not useful in all cases, since it misses about one-third of

the mutations that cause NF1 and NF2. These methods are supposed to improve over the

next few years. NF is not a rare disorder, it is the most common neurological disorder

caused by a single gene. NF can lead to disfigurement; blindness; deafness; skeletal

abnormalities; dermal, brain and spinal tumors; loss of limbs; malignancies; and learning

disabilities. The NF gene has been implicated in the development of several of the most

common and most serious human cancers.

Because NF1 and NF2 are genetically-determined disorders which affect more than

100,000 Americans; this makes NF more prevalent than Cystic Fibrosis, Hereditary

Muscular Dystrophy, Huntington’s Disease, and Tay Sachs combined.

To be diagnosed with NF1 you must have two of the following symptom’s:

six or more café au lait macules over 5 mm in greatest diameter in prepubertal

individuals and over 15 mm in greatest diameter in postpubertal individuals,

two or more neurofibromas of any type or one plexiform neurofibroma,

freckling in the axillary or inguinal regions, optic glioma ,

two or more Lisch nodules (iris harmartomas) ,and a distinctive osseous lesion such as

sphenoid dysplasia or thinning of long bone cortex with or without pseudoarthrosis .