Neurofibromatosis type I
Neurofibromatosis type I is a genetic disorder that causes tumors to grow along the nervous system and elsewhere in the body. One of the most common genetic disorders, neurofibromatosis type I affects approximately one out of every 3,000 births.
Definition & Facts
The disorder is caused by a genetic mutation at chromosome 17 that controls the division of cells. Most signs of neurofibromatosis type 1 are visible after birth, at the newborn and infant stages. However, there are symptoms that develop as a person grows and undergoes puberty and other hormonal and developmental changes.
The disorder's severity varies widely from person to person. While transmission is genetically linked and a parent with neurofibromatosis type I has a 50% likelihood of passing the disorder to their child, the severity of the disorder can vary greatly even among closely related family members.
Approximately 60% of neurofibromatosis type I cases are mild with few daily symptoms; 20% of cases are moderate, with mostly cosmetic impact and the remaining 20% are severe and greatly affect a person's quality of life.
Symptoms & Complaints
Skin symptoms include the development of café au lait spots, or patches of skin that are coffee-colored. Almost 95% of people who have neurofibromatosis type I have these spots from childhood to adulthood. The spots are painless and develop before a child is three years of age.
During their teens or early adult years, many people with neurofibromatosis type I will develop skin bumps under or on the skin. These are called neurofibromas, and are the result of benign tumors on nerve coverings. Some people only have a few of these while others cover large sections of the body.
Other symptoms of neurofibromatosis include musculoskeletal disorders like scoliosis and other spinal abnormalities. One limb may grow longer than another due to complicated neurofibromas that join together. Some people with neurofibromatosis type I also have eye diseases, including nodules in the eye.
The most common symptom of neurofibromatosis type I are learning disabilities and cognitive impairment, including attention deficit hyperactivity disorder (ADHD), speech delays, motor deficits, spatial issues and executive functioning problems.
Some people with neurofibromatosis type I also experience epilepsy and associated seizures. In addition, if a complicated neurofibroma called a plexiform neurofibroma is not treated and removed, it can, in rare cases, progress into cancer.
The cause of neurofibromatosis type 1 is the mutation of a gene called neurofibromin 1, or NF1. Genes are responsible for all characteristics of humans, and a mutation means that the DNA that makes up that gene has changed permanently. The NF1 gene is located on chromosome 17 and is responsible for the body's handling of a protein called neurofibromin. Usually, the protein will turn off the ongoing growth of tissue when it reaches the appropriate size.
However, when someone has neurofibromatosis type 1, this gene produces a protein that is not complete and is therefore ineffective at turning off nerve tissue growth. This leads to the development and growth of tumors along the nerves. Half of the people with neurofibromatosis type I inherit it from a parent who also has the gene.
Only one of two parents needs to have the gene for their child to also develop the condition. Every child that a person with neurofibromatosis type I bears has a 50% chance of developing the disorder, regardless of their sex. The other half of neurofibromatosis type I cases are due to spontaneous mutation with no known cause; in these cases, it does not indicate any particular likelihood of risk to future children of the same parents.
Diagnosis & Tests
Most cases of neurofibromatosis are made by looking for two or more of the key symptoms of the disorder. These factors are:
- More than five coffee-colored spots on the skin
- Freckles in the groin or armpits in a cluster
- More than one neurofibroma on or under the skin, or one plexiform neurofibroma on multiple nerve branches
- Optic nerve tumors called optic nerve gliomas
- Lisch nodules, or tiny spots in the iris of the eye that are brown
- Bone deformity, such as a bowed leg (genu varum)
- Family history of neurofibromatosis type I
Diagnosis may not be fully possible for children under five, although the disorder is easily diagnosed in older children and adults. If there is any confusion about the diagnosis, genetic testing can be performed for the NF-1 gene mutation.
Treatment & Therapy
Neurofibromatosis type I is not curable; instead, people with this disorder need ongoing monitoring to treat any emerging problems. Children will need an annual physical examination to look for the emergence of additional neurofibromas or changes in ones that are already there, to examine the eyes for nerve gliomas, to assess the bones for scoliosis, to check blood pressure, and to assess any issues relating to comprehension, reading, writing or other learning or cognitive concerns.
While skin spots can be covered with makeup, neurofibromas and particularly plexiform neurofibromas may require surgery, both because of the appearance of the growths and the pain they cause, as well as the cancer risk posed by plexiform neurofibromas.
Children with learning or cognitive disabilities will need to receive proper assessment and therapies for intervention and support (special education and speech therapy for example). If someone with neurofibromatosis type I develops scoliosis, or a very curved spine, back braces or surgery may be necessary in order to correct the curvature of the spine.
Prevention & Prophylaxis
During pregnancy, several genetic tests like amniocentesis can be used to check the likelihood of a fetus' development of neurofibromatosis type I. Pre-implantation genetic diagnosis, used along with in-vitro fertilization to scan embryos for those unaffected by the disorder, is also a possibility for people with the disorder considering pregnancy.