Neurofibromatosis is a disease that affects the development and growth of nerve cell tissues. It causes tumors to grow on nerves (neurofibromas) that lie on or under the skin anywhere in the body. The tumors are usually benign, which means that they are not cancerous. Even so, in some cases they can be disfiguring.

Symptoms of neurofibromatosis vary greatly, but generally they get worse over time. Some people have symptoms that are mild or not noticeable at all. In other people, neurofibromatosis causes significant disability.

Neurofibromatosis can cause skin changes, bone deformities, and other problems. The disease can cause developmental abnormalities. Patients with neurofibromatosis have a higher incidence of learning disabilities.

Neurofibromatosis has two different forms, type 1 (NF1) and type 2 (NF2). One abnormal gene causes each form.

Neurofibromatosis-1 is the more common form of neurofibromatosis, occurring in 1 in 4,000 births. Also known as von Recklinghausen disease, neurofibromatosis-1 is long lasting (chronic). It mostly affects nerves of the outer parts of the body (peripheral nervous system).

Neurofibromatosis-2 is less common, occurring in 1 in 40,000 births. Also known as bilateral acoustic neurofibromatosis, neurofibromatosis-2 mostly affects the central nervous system, causing tumors of the brain and spinal cord.

Neurofibromatosis is diagnosed through physical examination and by a complete review of the patient's medical history. Your doctor will look for changes in skin appearance and the presence of tumors or bone abnormalities. He or she may want to examine close family members (i.e., parents, siblings, and children) to look for signs of neurofibromatosis.

Symptoms begin at birth or early in life. People with neurofibromatosis-1 usually develop multiple birth marks, multiple neurofibromas, Lisch nodules in the eyes, and other complications.

Multiple Birthmarks

Several brown-colored birthmarks (caf-au-lait spots) are seen on this patient's skin.

Six or more light brown-colored birthmarks (cafe-au-lait spots) may be located anywhere on the body, including the mouth and tongue. The spots usually appear before about 9 years of age. They take various shapes and measure about 5 mm or more in size in young children and about 15 mm or more in adolescents.

Birthmarks alone do not indicate neurofibromatosis; some people who do not have neurofibromatosis may have up to three cafe-au-lait spots. Although they do not cause any medical problems, cafe-au-lait macules may increase in size and number with age, and become darker.

Other skin abnormalities in neurofibromatosis-1 include freckling in the armpit and groin areas (axillary and inguinal freckling).

Multiple Neurofibromas

In addition to several caf-au-lait spots, multiple small nodules (neurofibromas) are seen on this patient's lower back.

A person with neurofibromatosis-1 may have any number of neurofibromas-from none to hundreds. The tumors are usually small, painless, and slow growing. They may form skin nodules or masses of tissue deep in the body. Two or more lumps may appear at any age, especially around adolescence.

A single or few neurofibromas alone do not indicate neurofibromatosis; some people who do not have neurofibromatosis may have a neurofibroma. Tumors caused by neurofibromatosis-1 sometimes affect the brain and/or spinal cord. They may grow on nerves of the eye (optic glioma) and in rare instances may interfere with vision. Sometimes a tumor involves multiple nerves and grows to a very large size (plexiform neurofibroma). This is especially true on the face, arms, or legs. This type of tumor may become disfiguring, painful, or life-threatening, and it can cause weakness in the extremities.

Diagnosis of neurofibromatosis-2 may be difficult unless there is family history of the disease. Hearing loss that begins in the teens or early twenties is often the first symptom. People with neurofibromatosis-2 usually develop auditory nerve tumors or other complications.

Because symptoms of neurofibromatosis vary, the needs of the patient determine treatment. Doctors try to control symptoms and treat complications as they happen. Patients with neurofibromatosis may require coordinated care from physicians who are medical or surgical specialists. As an example, orthopaedic surgeons may help with the management of spinal deformities or limb size discrepancies. A team approach with knowledgeable caregivers and involved patients and families should help to optimize care.

There are some general guidelines.

• Children with neurofibromatosis often need regular medical evaluations to measure growth and blood pressure, and to examine skin, bones, the nervous system, vision, and hearing.
• Adults with neurofibromatosis often need yearly evaluations of the nervous system and hearing.
• Some people with neurofibromatosis have on-going medical issues, such as pain and disability. They may need life-long care from several medical and surgical specialists (i.e., orthopaedic surgeons, neurologists, dermatologists, and radiologists).
• Some people with neurofibromatosis visit multidisciplinary (many different doctors) neurofibromatosis clinics for comprehensive evaluations and management plans. They may receive treatment at the clinic or take a management plan back to their own doctor.

Sometimes, young children with abnormal spots have not yet developed neurofibromas. If this is the case, regular eye examinations and screening tools may help detect optic nerve gliomas for treatment before a child starts to lose his or her sight.

Most tumors caused by neurofibromatosis do not need treatment. But, tumors that are painful, disfiguring, rapidly growing, and impairing the function or compressing other body parts may need treatment. Some neurofibromas grow fast and may be at risk for becoming cancerous (malignant). Bone deformities may also need treatment.

The following are some of the treatment options available for abnormal tissue growth.

National Fibromatosis Foundation National Fibromatosis Foundation (http://www.nfinc.org)

National Institutes of Health National Institutes of Health (http://www.ninds.nih.gov/disorders/neurofibromatosis/neurofibromatosis.htm)

Reviewed by members of POSNA (Pediatric Orthopaedic Society of North America)