Neurofibromatosis (NF) is a condition that causes tumors to grow on nerve tissue, producing skin and bone abnormalities. NF is often diagnosed in childhood, occasionally in infancy but usually around 3-16 years of age. The effects of the disease vary widely. Some children might live almost unaffected by the condition. Although rare, others might be severely disabled.
Children with more severe forms of the disorder are usually diagnosed in infancy. Although there's no specific cure for NF, tumors can usually be removed and related complications can be treated. Children with NF may need some additional help in the classroom, because learning disabilities are seen in about half of children with the disease.
What Is Neurofibromatosis?
Neurofibromatosis is a neurocutaneous syndrome, it's passed down through the parents' genes, and it affects the brain, spinal cord, nerves, and skin.
Neurofibromatosis is defined by tumors, called neurofibromas, that grow along nerves in the body, or on or under the skin. As the tumors increase in size, they can press on vital areas of the body, causing problems in the way the body functions. It's not uncommon for neurofibromas to first appear during childhood, especially during puberty. One of the first noticeable signs of the disorder is almost always cosmetic disfigurement caused by these tumors (commonly called café-au-lait spots due to their distinctive light brown color). These distinctive spots can show up anywhere on the body.
Neurofibromas can often be removed. Although usually benign (noncancerous), they can sometimes become cancerous (in an estimated 5% of cases).
There are two types of neurofibromatosis, referred to as NF1 and NF2. NF1 is more common, occurring in one of every 4,000 births, and affecting an estimated 100,000 Americans. It is also known as von Recklinghausen disease.
The second type, NF2, is known as bilateral acoustic neurofibromatosis and is rarer, seen in one in 50,000 births. People with NF2 usually develop tumors on the nerves in their ears, causing hearing loss, eventual deafness, and problems with balance.
In both types of neurofibromatosis, the severity of the disorder varies greatly. In families where more than one person has NF, the disorder can progress with different physical signs and complications for each person. When NF is first diagnosed in a child, it isn't possible to know right away if the child will have a mild form of the disease or will develop severe complications.
What Causes Neurofibromatosis?
Both types of neurofibromatosis are autosomal dominant genetic disorders, which means a child has a 50% chance of inheriting the disease if either parent has NF. Neurofibromatosis can also be the result of a spontaneous change (mutation) in the genetic material of the sperm or egg at conception in families with no previous history of the disease. About half of cases of neurofibromatosis are inherited, and the other half result from genetic mutation.
There are two genes involved in causing neurofibromatosis. The NF1 gene is located on chromosome 17, and NF2 has been traced to chromosome 22. These findings are important because they may eventually lead to the development of a blood test or other genetic test to find out if a relative has NF.
Signs and Symptoms of Neurofibromatosis
NF1 is sometimes diagnosed in younger children, especially those with more severe forms of the disorder. One key to early diagnosis of mild NF is the appearance of café-au-lait spots on the child's skin.
Many people who do not have NF have a few café-au-lait spots. But if a young child has five or more of these spots, at least 1/4 inch in size (roughly the size of a dime), a doctor will likely look for other clues that may indicate NF, including neurofibromas - tumors on, under, or hanging off the skin - and Lisch nodules, tiny, noncancerous tumors on the iris (the colored part of the eye). Lisch nodules are of no clinical significance except that they help confirm a diagnosis of NF. Neurofibromas often become evident on various parts of the body, beginning at the arms, around 10 years of age. A child may also develop freckling in the folds of the skin of the armpit or groin or on other parts of the body where the skin creases.
Abnormalities of the skeleton, such as the thinning or overgrowth of the bones in the arms or lower leg, curvature of the spine (scoliosis), and other bone deformities may also be features of NF1.
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 (the nerves that carry electrical impulses from the inner ear to the brain, allowing us to hear) on one or both sides. Other symptoms of NF2 might be continuous ringing in the ears, headache, facial pain or weakness, and feeling unsteady or off balance.
How Is It Diagnosed and Treated?
Neurofibromatosis is usually diagnosed based on a combination of findings. A child must have at least two of the following signs to be diagnosed with NF1:
- café-au-lait spots of a certain number, size, and location
- the appearance of two or more neurofibromas (often resembling pea-sized bumps on the skin)
- Lisch nodules on the irises
- 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
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 children with symptoms of NF can have a larger than normal head circumference for a given age. Blood pressure will be monitored. Doctors will also take a detailed personal history, looking for signs of learning difficulties at home or at school.
To diagnose NF2, doctors will check for any evidence of hearing loss. They'll order audiometry (hearing tests) as well as imaging tests to look for tumors in the nerves of the ears, spinal cord, or brain. They'll also determine if there's a family history of NF2.
Genetic testing is now available for people with a family history of either NF1 or NF2, though such testing is still not 100% sensitive. Amniocentesis can sometimes determine if a woman's unborn child has the condition.
Treatment for NF1 includes removal of the neurofibromas for cosmetic purposes, treating the complications (see below), and getting intervention for children with learning disabilities. Children will be referred to appropriate medical specialists to monitor and treat any complications from the disease, which may include:
- seizures (up to 40% of children with NF1 have them)
- high blood pressure
- scoliosis
- speech impairment
- optic nerve tumors (which can cause vision problems leading to blindness)
- early or delayed onset of puberty
Rarely, neurofibromas can become cancerous (3% to 5% of cases). In these occurences, surgery, chemotherapy, or radiation may be necessary.
With NF2, surgeons will likely need to remove the auditory nerve tumors, which may cause deafness afterward. When parts of the auditory nerve are removed, hearing aids won't work. In 2000, the U.S. Food and Drug Administration approved an auditory brainstem implant for people with NF2 who have lost their hearing. This device transmits sound signals directly to the brain, enabling the person to hear certain sounds and speech.
Currently, researchers are conducting trials with medications in the hopes they'll be able to offer more treatment options.
Caring for Your Child
The first noticeable sign of neurofibromatosis is usually the presence of multiple café-au-lait spots. If your child has several of these spots, ask your doctor to do a thorough examination; he or she may need to screen your child for other signs of NF.
If your child has already been diagnosed with NF and you notice that a growing tumor is beginning to cause a problem, tell your child's doctor immediately.
One of the most important things you can do for your child after diagnosis of NF is to get early intervention if your child has learning disabilities. It also helps to seek out support groups that can provide your family with practical advice and support (click on the Additional Resources tab on the side of this article for more information).
Remember - most people (about 60%) diagnosed with NF1 have only relatively mild signs of the disorder, like café-au-lait spots and a few neurofibromas on the surface of the skin, which require little or no treatment. Children diagnosed with mild NF who remain fairly healthy into early adulthood are less likely to develop more serious complications of the disease later in life. Other children diagnosed with more serious forms of NF often have correctable complications and with appropriate help and support can lead happy and productive lives.
Updated and reviewed by: Louis E. Bartoshesky, MD, MPH
Date reviewed: July 2005
Reviewed by: Susan Stine, MD
