David A Thompson, MD
Fellow of the American Academy of Orthopaedic Surgeons
http://orthodoc.aaos.org/handmd
Guilford Orthopaedic & Sports Medicine Center
1915 Lendew Street
Greensboro, NC 27408 USA
Phone: 336-275-3325  | Fax: 336-275-5346
Copyright 2013 American Academy of Orthopaedic Surgeons
Neurofibromatosis

Neurofibromatosis is a disease that affects the development and growth of nerve cell tissues. It causes tumors to grow on nerves and can affect many systems in the body including the skin, skeleton, and brain. The tumors, called neurofibromas, are usually benign (noncancerous) and grow on nerves within the body, as well as on and under the skin.

Neurofibromatosis can cause skin changes, bone deformities, and other problems. In many cases, symptoms are present at birth or develop during childhood. Some people have symptoms that are mild or not noticeable at all. In other people, neurofibromatosis causes significant disability.

There is no cure for neurofibromatosis. Many symptoms, however, can be treated and managed. Children with more severe symptoms will naturally require more medical attention than children who have mild symptoms. In many cases, neurofibromatosis symptoms worsen as a patient ages.

Types of Neurofibromatosis

Neurofibromatosis Type 1 (NF1)

Neurofibromatosis Type 1 is the more common form of the disease, occurring in 1 in 3,000 to 4,000 births. Also known as von Recklinghausen disease, NF1 mostly affects nerves of the outer parts of the body (peripheral nervous system).

Symptoms begin at birth or early in life. People with NF1 may develop:

  • Multiple birth marks. Six or more light brown-colored birthmarks (cafe-au-lait spots) may be located anywhere on the body. 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.
  • Other skin abnormalities in NF1 include freckling in the armpit and groin areas (called axillary and inguinal freckling).

Light brown-colored birthmarks (café-au-lait spots) are a common sign of NF1.
  • Multiple neurofibromas. These tumors are usually small, painless, and slow growing. They may form nodules on the skin or masses deep in the body. Tumors may appear at any age, but often first occur around adolescence.
  • Tumors caused by NF1 sometimes affect the brain 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 (called a 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 arms or legs.

    Most NF1 tumors are benign; however, a small number become cancerous.

Neurofibromas and café-au-lait spots in a patient with NF1.
Reproduced with permission from Crawford AH, Schorry EK: Neurofibromatosis in children: the role of the orthopaedist. J Am Acad Orthop Surg 1999; 7:217-230.
  • Lisch nodules in the eyes. Lisch nodules are small brown tumors that often appear on the colored part of the eye (iris) in people with NF1. Lisch nodules cause no medical problems and may appear around 6 to 10 years of age.
  • Other complications. Learning disabilities affect many children with NF1. A child may be delayed in learning to walk or talk. Some children also show signs of mental retardation and/or speech problems, as well as short stature, oversized head (macrocephaly), hypertension; and an increased risk of cancer (malignancy).

In addition, NF1 can cause orthopaedic problems, including bone abnormalities. The most common orthopaedic problems in children with NF1 include:

  • Scoliosis. Scoliosis is a sideways curve of the spine. Instead of a straight line down the middle of the back, a spine with scoliosis curves, sometimes looking like a letter "S" or "C."
  • Scoliosis in children with NF1 can range from mild to severe curves. In many cases, the spinal curves progress slowly, at a similar rate as curves seen in children with idiopathic scoliosis. This type of scoliosis in children with NF1 is called nondystrophic.

    A less common form of scoliosis that affects children with NF1 is dystrophic scoliosis. It affects a smaller portion of the spine, but the curves worsen rapidly and can lead to serious deformity.

    In addition, children with NF1 may have kyphosis, which is a spinal curve that results in an abnormally rounded back.

(Left) Normal spine anatomy. (Right) Scoliosis can make the spine look more like the letters "C" or "S."
    (Left) An x-ray taken from the front of a patient with anterolateral bowing of the tibia. (Right) The same patient's leg in an x-ray taken from the side.
    Reproduced with permission from Lewis TR: Congenital pseudarthrosis of the tibia. Orthopaedic Knowledge Online Journal 2012. Accessed Apr 22, 2013.
  • Congenital pseudarthrosis of the tibia. Neurofibromatosis Type 1 can cause bones to grow abnormally. The tibia (shinbone) is the bone most commonly affected. In a small percentage of children with NF1, bowing of the tibia is one of the first signs of the disease, most often occurring before a child is two years old.
  • The tibia typically bows toward the front and to the outside of the leg (called an anterolateral bow). If the child has no other symptoms and has not yet been diagnosed with NF1, tibial bowing should prompt the pediatrician to fully evaluate the child for the disease. Although anterolateral bowing of the tibia may occur in patients without neurofibromatosis, it is associated with the disease 50% of the time.

    The bowing of the tibia makes it more vulnerable to a break, or fracture. Often, this fracture does not heal well due to the deformity of the bone, and may lead to a persistence of the fracture, known as a pseudarthrosis. Prevention of this sort of break is very important, as a pseudarthrosis of the tibia is very difficult to treat and requires surgery.

Neurofibromatosis Type 2 (NF2)

Neurofibromatosis Type 2 is less common, occurring in 1 in 25,000 to 40,000 births. Also known as bilateral acoustic neurofibromatosis, NF2 mostly affects the central nervous system, causing tumors of the brain and spinal cord.

Hearing loss that begins in the teens or early twenties is often the first symptom of NF2. People with NF2 may develop:

  • Auditory nerve tumors. Most people affected by NF2 develop tumors on the nerves needed for hearing (auditory nerves). Although the tumors are usually benign (noncancerous), they often lead to progressive hearing loss as they grow.
  • Other complications. Affected people may also have ringing in the ear(s), headaches, facial pain/numbness, and trouble with their balance.
Cause

NF1 and NF2 are genetic disorders. A separate abnormal gene causes each form of the disease.

Approximately half of the cases of neurofibromatosis are inherited. The other half are caused by a spontaneous mutation (change) of the gene.

Doctor Examination

Medical History and Physical Examination

Before a physical examination, your doctor will talk with you about your general health and current condition — or that of your child's, if you are a parent or family member. He or she will want to know what symptoms are present and when they began.

During the physical examination, your doctor will look for changes in skin appearance and the presence of tumors or bone abnormalities. Because neurofibromatosis is often inherited, your doctor may also want to examine close family members (parents, siblings, and children) to look for signs of neurofibromatosis.

Tests

Imaging and laboratory tests can help your doctor diagnose neurofibromatosis, as well as determine a treatment plan.

  • X-rays. These tests create clear pictures of dense structures, like bone. Your doctor may order x-rays to look for skeletal deformities.
  • Magnetic resonance imaging (MRI) scans. These scans create better pictures of soft structures. Your doctor may use MRI to find soft tissue tumors when they are still small. Tumors along the nerves of the eyes and ears may be easier to treat when discovered early.
  • Biopsy. In a biopsy, a tissue sample of the tumor is taken and examined under a microscope. This test is used to check for cancer cells.
General Treatment

Because there is no cure for neurofibromatosis, treatment focuses on managing the symptoms and preventing complications. Many types of medical specialists may be involved in the treatment of neurofibromatosis, depending on the patient's symptoms. A team approach with knowledgeable caregivers and involved patients and families should help to optimize care.

General Guidelines for Treatment

  • 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.
  • 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 eyesight.
  • Adults with neurofibromatosis often need yearly evaluations of the nervous system and hearing.
  • Some people with neurofibromatosis have ongoing 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.

Treatment of Tumors

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.

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

Surgery. Your doctor may remove a tumor by cutting it out of the body.

Radiation. Beams of energy (radiation) can shrink tumors and destroy cancer cells.

Chemotherapy. Chemotherapy is a drug treatment used to kill a tumor and any spread of cancer. It is often used initially to shrink a tumor and make it easier to remove with surgery.

Treatment for Orthopaedic Problems

The majority of people with NF1 will only experience moderate symptoms throughout their lives. Only a small percentage of NF1 patients will have orthopaedic problems that require treatment.

Scoliosis Treatment

Scoliosis associated with neurofibromatosis may require more intensive treatment than scoliosis that is not associated with the disease.

Bracing. If your child has a curve of 15° to 25° and is still growing, your doctor may recommend wearing a brace. Although bracing will not straighten scoliosis curves, it may slow the progress of the curves or prevent them from getting worse.

Spinal fusion. To treat severe scoliosis caused by NF1, a doctor may recommend surgery.

The operation for scoliosis is a spinal fusion. This is essentially a "welding" process. The basic idea is to realign and fuse together the curved vertebrae so that they heal into a single, solid bone. Implants made up of screws, rods, hooks, or wires will keep the bones in place while the fusion heals.

(Left) This x-ray shows a severe scoliosis curve in a 14-year-old boy with NF1. (Right) The same patient's spine after spinal fusion surgery.
Reproduced with permission from Feldman DS, Jordan C, Fonseca L: Orthopaedic manifestations of neurofibromatosis type 1. J Am Acad Orthop Surg 2010; 18:346-357.

Treatment for Pseudarthrosis of the Tibia

Children with NF1 who have tibial bowing require special braces that are intended to protect the bone from fracture. If the bone breaks, surgery is frequently required.

During the operation, the bone fragments are first repositioned (reduced) into the best alignment possible, then held together with special implants.

These fractures, often delayed in their healing and referred to as pseudarthroses, are difficult to treat, and the surgeon may need to apply special bone grafts to stimulate healing. Refracture is common. If the bone does not heal despite several surgical interventions, then the surgeon, patient, and patient's family may need to consider amputation.

(Left): An x-ray of a pseudarthrosis of the tibia in a 5-year-old child. (Right): The fracture is held together with a rod inside the bone.
Reproduced with permission from Lewis TR: Congenital pseudarthrosis of the tibia. Orthopaedic Knowledge Online Journal 2012. Accessed Apr 22, 2013.
Living with Neurofibromatosis

Some people with neurofibromatosis and other genetic disorders may experience emotional or psychological issues as a result of their illness. They may become isolated and withdrawn because they feel different from others. They may have emotional and/or social pain concerning their appearance. They may experience fear of the complications and they may even wonder whether to have children.

Many parents of children diagnosed with neurofibromatosis may also be suffering with feelings of shock, anger, sadness, confusion, guilt, and anxiety.

Family counseling, genetic counseling, and support groups may help people with neurofibromatosis and their families. These options can provide support, answer questions, and help with plans for the future.

Statistic Source: Neurofibromatosis Fact Sheet. The National Institute of Neurological Disorders and Stroke. Publication date May 2011.

Last reviewed: May 2013

Reviewed by members of the Pediatric Orthopaedic Society of North America

AAOS does not endorse any treatments, procedures, products, or physicians referenced herein. This information is provided as an educational service and is not intended to serve as medical advice. Anyone seeking specific orthopaedic advice or assistance should consult his or her orthopaedic surgeon, or locate one in your area through the AAOS "Find an Orthopaedist" program on this website.
Copyright 2013 American Academy of Orthopaedic Surgeons
Related Links
Scoliosis Frequently Asked Questions (http://orthoinfo.aaos.org/topic.cfm?topic=A00626)
Fractures (Broken Bones) (http://orthoinfo.aaos.org/topic.cfm?topic=A00139)
Nonunions (http://orthoinfo.aaos.org/topic.cfm?topic=A00374)
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