Diagnosis of NF1

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Neurofibromas, the most common tumors in NF, are benign growths which typically develop on or just underneath the surface of the skin but may also occur in deeper areas of the body. Neurofibromas, which are composed of tissue from the nervous system (neuro) and fibrous tissue (fibroma), usually develop around puberty although they may appear at any age. The tumors are not contagious. Nodule-like surface tumors are known as dermal neurofibromas. Plexiform neurofibromas grow diffusely under the skin surface or in deeper areas of the body.

 

The presence of multiple neurofibromas is an important diagnostic sign of NF. Single neurofibromas may occasionally occur in people who do not have NF. The number of neurofibromas varies widely among affected individuals from only a few to thousands. There is no way at present to predict how many neurofibromas a person will develop. Dermal neurofibromas rarely, if ever, become cancerous. Such a change, called a malignant transformation, may occur, although very rarely, in plexiform tumors. Therefore, it is important that patients be in the care of an NF specialist. Some neurofibromas, depending on their location and size, can be removed surgically if they become painful or infected, or cosmetically troublesome. A new tumor sometimes appears where one has been removed, particularly if that tumor was not removed completely. There is no evidence that removal of growths will increase the rate of appearance of new growths, or can cause incompletely removed tumors to change from benign to cancerous.

Café-au-lait spots, the most common sign of NF, are the flat, pigmented spots on the skin, which are called by the French term for coffee (café) with milk (lait) because of their light tan color. In darker-skinned people, café-au-lait spots appear darker in color than surrounding skin. People with NF almost always have six or more café-au-lait spots. (Fewer café-au-lait spots may occur in people who do not have NF; in fact, about 10% of the general population has one or two café-au-lait spots). The size of the spots that identify NF varies from 1/4 inch (5 mm) in children and 3/4 inch (15 mm) in adults to several inches in diameter or larger. In general, with few exceptions, tumors are not more likely to appear where there are spots. Café-au-lait spots are usually present at birth in children who have NF or, generally, appear by two years of age. The number of spots may increase in childhood and occasionally later in life. The spots may be very light in color in infants and usually darken as the child gets older. Smaller pigmented spots, which may be difficult to distinguish from ordinary freckles, may also be present in people with NF. In those who do not have NF, freckling usually occurs in areas of skin exposed to sun. With NF, café-au-lait spots and freckling are present in other areas as well, including the armpit (axilla), where small spots are called axillary freckling, and the groin. Axillary freckling is not seen in every person with NF, but when present it is considered strong evidence of NF.

Iris nevi (also called Lisch nodules) are clumps of pigment in the colored part of the eye (iris). Iris nevi, which usually appear around puberty, can be distinguished from iris freckles (commonly seen in people without NF) by a simple and painless procedure called a slit-lamp examination, which is typically performed by an ophthalmologist. Iris nevi do not cause medical problems and do not affect vision. The presence of iris nevi can occasionally be helpful in confirming the diagnosis of NF.

How Do I Know I Have NF1?

Only a knowledgeable physician can answer that question. In the language of experts, the diagnostic criteria for NF1 are having two or more of the following criteria, provided that no other disease accounts for the findings.

  1. Family history of NF1
  2. 6 or more light brown ("cafe-au-lait") spots on the skin
  3. Presence of two or more pea-sized bumps (neurofibromas) on the skin or one or more plexiform neurofibroma (larger areas on the skin that look swollen)
  4. Freckling under the arms or in the groin area
  5. Pigmented bumps on the eye's iris (Lisch nodules)
  6. Skeletal abnormalities such as tibial dysplasia (bowing of the legs), or thinning of the shin bone
  7. Tumor on the optic nerve that may interfere with vision

Laboratory tests are now available in most cases to determine whether a person has NF 1 and 2. Gene linkage testing is available for families with NF1 and NF2. Direct gene testing is currently available for NF1 and may be available in the near future for NF2. These tests may be used for presymptomatic diagnosis. To find out whether you qualify for such tests, consult your nearest NF clinic or center. Occasionally, the signs of NF are not easy to identify. For example, café-au-lait spots may be so pale that they are not noticeable in ordinary light. For this reason, members of families in which NF has occurred are often concerned about whether they may have the NF gene, even if they have no obvious signs of the disorder. An examination by a physician familiar with the signs of NF is the best way currently available to determine whether NF is present. Examination of the skin may be helped by use of an ultraviolet light (Wood's lamp) which can occasionally identify very light café-au-lait spot pigmentation and can also help to differentiate this from pigmentation due to fungal infections of the skin. An examination that reveals no signs of NF can be considered reassuring, since it is extremely rare for an individual to inherit the gene and to show no detectable sign of the disorder.

Variability of NF

NF is an extremely variable disorder. The severity of NF ranges from extremely mild cases in which the only signs of the disorder in adulthood may be multiple café-au-lait spots and a few dermal neurofibromas, to more severe cases in which one or more serious complications may develop. The complications of NF are discussed in the next section. There is no way to predict who will have a mild case and who will develop serious complications. The majority of people with NF (probably 60%) have mild forms of the disorder. Another 20% have correctable problems and another 20% have serious and persistent problems. Many of the serious problems in NF mentioned below are evident at birth or develop prior to adolescence. These may include congenital defects of the bone, scoliosis, optic glioma and neurological impairment leading to learning disability or mental retardation. People with NF who have reached adulthood without having these problems are unlikely to develop them.

Complications of NF1

  1. Disfigurement.

    NF1 can result in disfigurement in a number of ways. Skin neurofibromas may develop on the face or on exposed areas of the arms or legs. The larger and deeper plexiform neurofibromas may grow around the eye or eyelid, or affect growth of one side of the face. Scoliosis, or curvature of the spine (see below), can affect appearance when it is severe. Growths can occur around the nipple (periareolar neurofibromas) which may be distressing. Rarely, an overgrowth of skin or bone causes enlargement of an arm or leg.

    In some people, the size or number of neurofibromas increases during puberty and pregnancy, reflecting a possible hormonal effect.

    There is no evidence that diet, exercise or vitamins affect the growth of neurofibromas.

    While disfigurement, and fear of disfigurement, are often major concerns for those with NF1, not everyone reacts the same way to complications that affect appearance. Some people find that café-au-lait spots or a minimum number of skin neurofibromas are hard to live with, while others are able to tolerate more severe involvement. Those who are upset by the problems of disfigurement often find support and discussion groups to be helpful. If surgery is desired, primarily to improve appearance, a plastic surgeon may be consulted to determine whether a particular tumor can be removed. Plexiform neurofibromas around the eye are often managed jointly by an eye (ophthalmic) surgeon and a plastic surgeon.

  2. Scoliosis.

    Lateral curvature of the spine, known as scoliosis, is common in NF1. In most cases it is mild. Scoliosis usually appears in early childhood. A child with scoliosis will need periodic spine X-rays and physical examinations to determine whether corrective measures are needed. In some cases, a brace may be used to prevent progression of the problem. More serious cases may require corrective surgery.

  3. Learning Disabilities.

    Learning disabilities, often first noticed when the child starts school, are specific problems with reading, writing and the use of numbers which occur in children who have normal intelligence. Learning disabilities are more common in children with NF1 than in other children, and may be associated with hyperactivity. A child suspected of having a learning disability can be evaluated by a psychologist, child neurologist or professional with special knowledge of this problem. Many school systems provide referrals to specialists in these fields.

  4. Large Heads.

    Children and adults with NF1 often have large head circumference, which usually does not indicate any significant medical problem. Very rarely, large head circumference results from hydrocephalus, a serious problem which may require surgery. Imaging of the brain with CT scan or MRI can help determine if head enlargement is serious or not. Head circumference in children with NF1 should be measured periodically.

  5. Optic Gliomas.

    An optic glioma is a tumor of the optic nerve (the nerve which controls vision). This tumor, which fortunately is uncommon, usually appears in childhood and is first noticed because of poor or failing vision or bulging of the eye. Children with NF1 should have routine eye examinations by an ophthalmologist, neurologist or physician familiar with this problem. Treatment for this condition includes surgery and radiation therapy.

  6. Congenital Defects of Bone.

    The variety of bone defects seen in NF1 are usually evident at birth. Most are uncommon. Defects can occur in almost any bone, but are seen most often in the skull and limbs. They include:

    • Congenital absence of the orbital wall, the bone normally surrounding the eye. Its absence may cause slight bulging of the skin around the eye.
    • Bowing of the leg bones below the knee (tibia or fibula). These bones may be thinner than normal and bowed. If a fracture occurs, healing may be slow or incomplete. Incomplete healing, called pseudarthrosis, may also affect the bones in the forearm (radius or ulna), but this occurs very rarely. This is a difficult problem, which requires the supervision of an orthopedic surgeon.
  7. High Blood Pressure (Hypertension).

    People with NF1 can have hypertension for reasons completely unrelated to NF1. However, two rare problems associated with NF1 may result in hypertension: renal artery stenosis (blockage of the artery to the kidney), and pheochromocytoma, a rare and usually benign tumor of the adrenal gland. Both of these problems are treatable. Because of these possible problems, it is important that routine physical exams for children and adults with NF1 include blood pressure checks.

Rare Complications of NF1

The complications mentioned below occur in 1%, or less, of people with NF1. The listing is intended to inform you of the rare complications possible in NF1, but it should be emphasized that very few people with NF1 will experience any of these symptoms.

  1. Early or late onset of puberty.
  2. Problems with growth (too short or too tall).
  3. Mental retardation.
  4. Epilepsy (seizure disorder).
  5. People with NF1 may have a somewhat higher risk for certain rare malignant tumors that occur in the brain, nerves or spinal cord, but probably have the same risk for "common" cancers (such as lung, breast, stomach, etc.) as the general population.
  6. Brain tumors (other than acoustic neuroma and optic glioma).
  7. Cerebrovascular occlusion (stroke). This refers to blockage of the blood vessels supplying the brain.
  8. Itching of the skin (pruritus). This can be treated with antihistamine medication.
  9. Hormonal Effects on Neurofibromatosis
    A number of patients request information on the effects of hormones on the symptoms of NF. There have been numerous reports of worsening of symptoms as patients experience the hormonal changes associated with puberty. In addition, patients report increases in the number and size of neurofibromas during pregnancy. Changes may also occur as a patient enters menopause. Patients wonder about the effects of birth control pills or hormone replacement therapy on their NF symptoms. There has NOT been a systematic research study to accurately describe or quantify the effect of hormones on tumors or other symptoms of NF. If you experience any changes and are concerned about the role hormones may play in your specific case of NF, you should discuss these concerns with your physician or contact a nearby NF Clinic.

Genetics Testing for NF1

Medical Genomics Laboratory at University of Alabama, Birmingham: Patients and families interested in direct gene testing for NF1 can contact the Medical Genomics Laboratory at UAB, phone  (205) 934-5562. More information on testing is available at the MGL website.

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