Neurofibromatosis type 1
Other Names for this Disease
- Recklinghausen's disease
- Type 1 neurofibromatosis
- Von Recklinghausen disease
What are the signs and symptoms of neurofibromatosis type 1 (NF1)?
What causes neurofibromatosis type 1 (NF1)?
How is neurofibromatosis type 1 (NF1) inherited?
How is neurofibromatosis type 1 diagnosed?
How might neurofibromatosis type 1 (NF1) be treated?
Beginning in early childhood, almost all people with NF1 have multiple café-au-lait spots, which are flat patches on the skin that are darker than the surrounding area. These spots increase in size and number as the individual grows older. Freckles in the underarms and groin typically develop later in childhood.
The eyes can also be affected by NF1. During childhood, benign growths called Lisch nodules often appear in the colored part of the eye (iris). Lisch nodules do not interfere with vision. Some affected individuals also develop tumors that grow along the nerve leading from the eye to the brain (the optic nerve). These tumors, which are called optic gliomas, may lead to reduced vision or total vision loss. In some cases, optic gliomas have no effect on vision.
Most adults with NF1 develop neurofibromas, which are noncancerous (benign) tumors that are usually located on or just under the skin. These tumors may also occur in nerves near the spinal cord or along nerves elsewhere in the body. Some people with NF1 develop cancerous tumors that grow along nerves. These tumors, which usually develop in adolescence or adulthood, are called malignant peripheral nerve sheath tumors. People with NF1 also have an increased risk of developing other cancers, including brain tumors and cancer of blood-forming tissue (leukemia).
Additional signs and symptoms of NF1 include high blood pressure (hypertension), short stature, an unusually large head (macrocephaly), and skeletal abnormalities such as an abnormal curvature of the spine (scoliosis). Although most people with NF1 have normal intelligence, learning disabilities and attention deficit hyperactivity disorder (ADHD) occur frequently in affected individuals.
The NF1 gene provides instructions for making a protein called neurofibromin. This protein is produced in many cells, including nerve cells and specialized cells surrounding nerves (oligodendrocytes and Schwann cells). Neurofibromin acts as a tumor suppressor, which means that it keeps cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in the NF1 gene lead to the production of a non-functional version of neurofibromin that cannot regulate cell growth and division. As a result, tumors such as neurofibromas can form along nerves throughout the body. It is unclear how mutations in the NF1 gene lead to the other features of neurofibromatosis type 1, such as café-au-lait spots and learning disabilities.
Unlike most other autosomal dominant conditions, in which one altered copy of a gene in each cell is sufficient to cause the disorder, two copies of the NF1 gene must be altered to trigger tumor formation in neurofibromatosis type 1. A mutation in the second copy of the NF1 gene occurs during a person's lifetime in specialized cells surrounding nerves. Almost everyone who is born with one NF1 mutation acquires a second mutation in many cells and develops the tumors characteristic of neurofibromatosis type 1.
- Six or more light brown spots on the skin (“cafe-au-lait” spots), measuring more than 5 millimeters across in children, or more than 15 millimeters across in adolescents and adults
- Two or more neurofibromas, or one plexiform neurofibroma (a neurofibroma that involves many nerves)
- Freckling in the area of the armpit or the groin
- Two or more growths on the iris of the eye (known as Lisch nodules or iris hamartomas)
- A tumor on the optic nerve (optic glioma)
- Abnormal development of the spine (scoliosis), the temple (sphenoid) bone of the skull, or the tibia (one of the long bones of the shin)
- A parent, sibling, or child has been diagnosed with NF1
Symptoms such as café-au-lait spots, neurofibromas, Lisch nodules, and freckling are often seen at birth or shortly afterwards, and almost always by the time a child is 10 years old. Because many features do not develop until a person is older, it can take several years to make a diagnosis.
- Neurofibromatosis type 1. Genetics Home Reference. March 2007; http://ghr.nlm.nih.gov/condition=neurofibromatosistype1. Accessed 3/18/2011.
- NF1 gene. Genetics Home Reference Website . 2007; http://ghr.nlm.nih.gov/gene/NF1. Accessed 11/9/2011.
- JM Friedman. Neurofibromatosis 1. GeneReviews. May 3, 2012; http://www.ncbi.nlm.nih.gov/books/NBK1109/. Accessed 2/28/2014.
- Neurofibromatosis Fact Sheet. National Institute of Neurological Disorders and Stroke Website. January 13, 2012; http://www.ninds.nih.gov/disorders/neurofibromatosis/detail_neurofibromatosis.htm. Accessed 10/2/2013.