Three distinct types of neurofibromatosis exist, each with different signs and symptoms.
Neurofibromatosis 1 (NF1)
Neurofibromatosis 1 (NF1) usually appears in childhood. Signs and symptoms include:
- Flat, light brown spots on the skin. These harmless spots, also called cafe au lait (ka-FAY oh LAY) spots, are common in many people. If you have more than six of them, it's a strong indication of NF1. In NF1, cafe au lait spots are usually present at birth or appear during the first years of life and then stabilize. They aren't serious but can sometimes be a cosmetic concern.
- Freckling in the armpits or groin area. Freckling usually appears by age 4 or 5.
- Soft bumps on or under the skin (neurofibromas). Neurofibromas are benign tumors that can be located anywhere in the body. Many people develop tumors in the skin or under the skin, but neurofibromas can also grow inside of the body. Sometimes, a growth will involve multiple nerves (plexiform neurofibroma).
- Tiny bumps on the iris of your eye (Lisch nodules). Lisch nodules — harmless lesions in your eye — can't easily be seen just by looking at them, and they don't affect your vision. However, your doctor can detect these lesions using a special instrument.
- Bone deformities. Abnormalities in the way bones grow and a deficiency in bone mineral density can cause bone deformities such as a curved spine (scoliosis) or bowed lower leg.
- Learning disabilities. Impaired thinking skills (cognition) are common in children with NF1, but are usually mild. Children may have difficulty with language and visual-spatial skills. Children with NF1 often may have a specific learning disability, such as attention-deficit/hyperactivity disorder (ADHD).
- Larger than average head size. Children with NF1 tend to have a larger than average head size and higher brain volume, but it's unknown whether this is related to cognitive impairment.
- Short stature. Children with NF1 often have a short stature and are below average in height.
Neurofibromatosis 2 (NF2)
Neurofibromatosis 2 (NF2) is much less common than NF1. Signs and symptoms of NF2 usually result from the development of vestibular schwannomas (also known as acoustic neuromas) in both ears.
These benign tumors grow on the nerve that carries sound and balance information from the inner ear to the brain (the eighth cranial nerve). Resulting signs and symptoms generally appear in the late teen and early adult years and may include:
- Gradual hearing loss
- Ringing in the ears
- Poor balance
In some cases, NF2 can lead to growth of schwannomas in other nerves of the body, including the cranial, spinal, visual (optic) and peripheral nerves. Associated signs and symptoms may include:
- Facial drop
- Numbness and weakness in the arms or legs
- Balance difficulties
In addition, NF2 may result in vision problems due to abnormal growth on the retina (mostly in children) or due to the development of cataracts.
Schwannomatosis is a rare form of neurofibromatosis only recently recognized. It rarely affects people before their 20s or 30s. Schwannomatosis causes painful tumors called schwannomas to develop on cranial, spinal and peripheral nerves, but not on the nerve that carries sound and balance information from the inner ear to the brain (the eighth cranial nerve).
Because tumors don't grow on this nerve, schwannomatosis doesn't cause hearing loss, making it different from NF2. As with NF2, though, schwannomatosis doesn't cause cognitive impairment. Schwannomatosis mainly causes chronic pain, which can occur anywhere in your body.
When to see a doctor
If you notice signs or symptoms of neurofibromatosis in your child or yourself, call your doctor for an appointment or bring it up at your next visit. The tumors associated with neurofibromatosis are often benign and slow-growing. So although it's important to obtain a timely diagnosis and monitor for complications, the situation isn't an emergency.
Neurofibromatosis is caused by genetic defects (mutations) that either are passed on by a parent or occur spontaneously at conception. Each form of neurofibromatosis is caused by mutations in different genes.
Neurofibromatosis 1 (NF1)
The NF1 gene is located on chromosome 17. Normally, this gene produces a protein called neurofibromin, which is abundant in nervous system tissue and helps regulate cell growth. A mutation of the NF1 gene causes a loss of neurofibromin, which allows cells to grow uncontrolled.
Neurofibromatosis 2 (NF2)
A similar problem occurs with NF2. The NF2 gene is located on chromosome 22, which produces a protein called merlin. A mutation of the NF2 gene causes loss of merlin, which also leads to uncontrolled cell growth.
Schwannomatosis may be associated with a mutation of the SMARCB1 gene located on chromosome 22. Other gene mutations may be involved in schwannomatosis. The occurrence of schwannomatosis may be inherited or may be sporadic (spontaneous), but these are not known yet.
The biggest risk factor for neurofibromatosis is a family history of the disorder. About half of NF1 and NF2 cases are inherited. The remaining cases result from spontaneous mutations that occur at conception.
NF1 and NF2 are both autosomal dominant disorders, which means that any child of a parent with the disorder has a 50 percent chance of inheriting the genetic mutation.
The inheritance pattern for schwannomatosis is less clear. Researchers currently estimate that the risk of inheriting schwannomatosis from an affected parent is about 15 percent.
Complications of neurofibromatosis vary, even within the same family. Generally, complications result from tumor growth distorting nerve tissue or pressing on internal organs.
Doctors can't predict whether your disease will progress, but most people with neurofibromatosis experience a mild or moderate form of the disorder, regardless of type.
Neurofibromatosis 1 (NF1) complications
Common complications of NF1 include:
- Neurological problems. Learning and thinking (cognitive) difficulties occur in up to 60 percent of NF1 cases and are the most common neurological problem associated with NF1. Uncommon complications associated with NF1 include epilepsy, stroke and buildup of excess fluid in the brain (hydrocephalus).
- Concerns with appearance. Visible signs of neurofibromatosis — such as extensive cafe au lait spots, numerous nerve tumors (neurofibromas) in the facial area or large neurofibromas — can cause anxiety and emotional distress, even if they're not medically serious.
- Skeletal problems. Some children have abnormally formed bones, which can result in bowing of legs and fractures that sometimes don't heal. NF1 can cause curvature of the spine (scoliosis) that may need bracing or surgery. NF1 is also associated with decreased bone mineral density, which increases your risk of weak bones (osteoporosis).
- Visual difficulties. Occasionally in children, a tumor (optic pathway glioma) growing on the nerve leading from the eye to the brain (optic nerve) can cause visual problems.
- Increase in neurofibromas. Hormonal changes associated with puberty, pregnancy or menopause may cause an increase in neurofibromas. Most women with NF1 have healthy pregnancies but will likely need monitoring by an obstetrician familiar with NF1, in addition to their NF1 specialists.
- Cardiovascular problems. People with NF1 have an increased risk of high blood pressure and, rarely, blood vessel abnormalities.
- Cancer. Less than 10 percent of people with NF1 develop cancerous (malignant) tumors. These usually arise from neurofibromas under the skin or plexiform neurofibromas involving multiple nerves.
Monitor neurofibromas vigilantly for any change in appearance, size or number. Changes may indicate cancerous growth. The earlier a malignancy is detected, the better the chances for effective treatment.
People with NF1 also have a higher risk of other forms of cancer, such as breast cancer, leukemia, brain tumors and some types of soft tissue cancer.
Neurofibromatosis 2 (NF2) complications
NF2 may cause complications including:
- Vestibular schwannomas in both ears, which may grow over time
- Partial or total deafness
- Facial nerve damage
- Visual difficulties
- Skin lesions
- Weakness or numbness in the extremities
- Multiple benign brain tumors (meningiomas) or spinal tumors requiring frequent surgeries
The pain caused by schwannomatosis can be debilitating and may require surgical treatment or management by a pain specialist.