Neurofibromatosis (NF) is a genetic disease in which multiple soft tumors
(neurofibromas) develop under the skin and throughout the nervous system.
Various sized tumors may grow on the nerves in or leading away from the
brain and spinal cord (peripheral nerves) and in the vascular system
(veins and arteries) and other organ systems. There are two types of NF:
NF-1, also called vonRecklinghausen NF, and NF-2, also called acoustic NF
(sometimes bilateral acoustic NF or BAN). NF-1 is more common,
representing 90 percent of all cases, while NF-2 is diagnosed in 10
percent of NF cases.
Neural crest cells are primitive cells that are present as part of the
nervous system during fetal development. These cells eventually turn into
In both types of NF, a genetic defect causes these neural crest cells to
develop abnormally, resulting in numerous tumors and malformations of the
nerves, bones, and skin.
NF-1 affects nerves throughout the body, occurring as groups of soft,
fibrous swellings that grow on nerves in the skin, brain, and spinal cord
(central nervous system), muscles, and bone. Severe disfigurement can
result from the development of these tumors as the disease progresses and
bone deformities may occur as well.
NF-2 is a rare type of NF in which multiple tumors grow on the cranial
(head) and spinal nerves and other growths can occur in the brain and
spinal cord. Tumor growth (schwannoma) on the nerves to the ears (auditory
nerves) is most characteristic of NF-2. Disfigurement does not occur
although hearing and visual problems are typical.
NF-1 is a common genetic disorder that occurs in about one of every 4,000
births worldwide. NF-2 is rare, occurring in one of every 40,000 births.
Children with a
history of neurofibromatosis are at highest risk for having either form
of the condition.
Causes and symptoms
Both forms of neurofibromatosis are caused by a defective gene. NF-1 is
due to a defect on chromosome 17; NF-2 results from a defect on chromosome
22. Both of these disorders are inherited in a dominant fashion, which
means that anyone who receives just one defective gene will have the
disease. However, a family pattern of NF is only evident for about half of
all cases of NF. The other cases of NF occur due to a spontaneous mutation
(a permanent change in the structure of a specific gene). Once such a
spontaneous mutation has been established in an individual, however, it
can then be passed on to any offspring. The chance of a person with NF
passing on the NF gene to a child is 50 percent.
NF-1 has a number of possible signs and can be diagnosed if any two of the
following are present:
Very high rates of speech impairment, learning disabilities, and attention
deficit disorder occur in children with NF-1. Other complications include
the development of a
or the abnormal accumulation of fluid within the brain (
). A number of cancers are more common in individuals who have NF-1. These
include various types of malignant brain tumors, as well as leukemia and
cancerous tumors of certain muscles (rhabdomyosarcoma), the adrenal glands
(pheochromocytoma), or the kidneys (
Patients with NF-2 do not necessarily have the same characteristic skin
symptoms that appear in NF-1. The characteristic symptoms of NF-2 are due
to tumors along the acoustic nerve that result in nerve dysfunction and
the loss of hearing. The tumor may also spread to neighboring nervous
system structures, causing weakness of the muscles of the face,
, poor balance, and uncoordinated walking. Cloudy areas on the lens of the
eye (cataracts) frequently develop at an unusually early age. As in NF-1,
the chance of brain tumors developing is unusually high.
A history of either form of NF in the child's parent or sibling is
reason to consult a physician. The presence of any of the symptoms
associated with NF-1 or NF-2 should be investigated by a physician as
well, particularly spots on the skin or small movable lumps under the skin
and visual disturbances, memory loss, or difficulty maintaining balance.
Hearing loss may be the first sign of NF-2 but can also be due to other
Diagnosis is based on characteristic symptoms and physical examination.
Diagnosis of NF-1 requires that at least two of the characteristic signs
are present. Diagnosis of NF-2 requires the presence of either a nodule or
mass (tumor) on the acoustic nerve or another distinctive nervous system
tumor, which may only be identifiable
through imaging studies. An important diagnostic clue for either NF-1 or
NF-2 is the known presence of the disorder in a child's parent or
sibling. Gene studies may be done to detect abnormalities on chromosomes
17 and 22.
Diagnosis of NF-1 will be confirmed by manipulation of the skin to reveal
moveable, small, solid lumps (nodules) and the presence of coffee-colored
spots on the skin of the trunk and pelvis. The spots may appear in
childhood and typically become more noticeable in young adults. Two or
more nodules and six or more discolored spots are usually definitive for a
diagnosis of NF-1. Curvature of the spin (scoliosis) may be present,
elevated blood pressure, and abnormalities in height, weight, and head
size may also be noticed on physical examination.
Diagnosis of NF-2 also relies on manipulation of the skin to indicate the
presence of nodules and evaluation of hearing and vision to determine any
X rays, CT scans, and MRI scans are performed to track the
development/progression of tumors in the brain and along the nerves.
Auditory evoked potential testing (the electric response evoked in the
cerebral cortex by stimulation of the acoustic nerve) may be helpful to
determine involvement of the acoustic nerve, and EEG (
, a record of electrical currents in the brain) may be needed for children
who have possible seizures. As the disease progresses, hearing and vision
are carefully monitored and imaging studies of the bones are frequently
done to watch for the development of deformities.
There is no standard treatment for either type of neurofibromatosis. To
some extent, the symptoms of NF-1 and NF-2 can be treated individually.
Skin tumors can be surgically removed. Some brain tumors and tumors along
the nerves, can be surgically removed or treated with chemotherapeutic
drugs or x-ray treatments (radiation therapy). Twisting or curving of the
spine and bowed legs may be corrected to some degree by surgical treatment
or the wearing of a special brace. Social adjustment problems are common
among young children with physical deformities caused by the condition.
—A microscopic thread-like structure found within each cell of
the human body and consisting of a complex of proteins and DNA. Humans
have 46 chromosomes arranged into 23 pairs. Chromosomes contain the
genetic information necessary to direct the development and functioning
of all cells and systems in the body. They pass on hereditary traits
from parents to child (like eye color) and determine whether the child
will be male or female.
—A permanent change in the genetic material that may alter a
trait or characteristic of an individual, or manifest as disease. This
change can be transmitted to offspring.
—A soft tumor usually located on a nerve.
—A growth of tissue resulting from the uncontrolled proliferation
There is no known way to prevent NF cases that occur as a result of
spontaneous change in the genes (mutation). New cases of inherited NF can
be prevented with careful genetic counseling. Parents with NF can be
encouraged to understand that each of his or her offspring has a 50
percent chance of also having NF. When a parent has NF, and the specific
genetic defect causing the parent's disease has been identified,
tests can be performed on the fetus (developing baby) during pregnancy.
Procedures such as
or chorionic villus sampling allow small amounts of the baby's
cells to be removed for examination. The tissue can then be examined for
the presence of the parent's genetic defect. Some families choose
to use this information in order to prepare for the arrival of a child
with a serious medical problem. Other families may choose not to continue
Parents may worried about the development of deformities associated with
NF-1. Social workers and psychologists can be consulted about possible
counseling for children with the disease, helping them to cope with
changes in their bodies that may be hard to accept. Hearing loss and
visual disturbances associated with NF-2 are usually not reversible and
specialists can be consulted about possible therapies to improve
functioning in existing sight or hearing senses. Surgery to remove tumors
may require the provision of educational information for both parents and
children so that the procedure and possible complications are understood
ahead of time.
March of Dimes Birth Defects Foundation.
Resource Center, 1275 Mamaroneck Ave., White Plains, NY 10605. Web site:
National Neurofibromatosis Foundation Inc.
95 Pine St., 16th Floor, New York, NY 10005. Web site:
Available online at
(accessed October 12, 2004).
Available online at http://www.rfinc.org/ (accessed October 12,