Genetics Northern California

Neurofibromatosis 1

Neurofibromatosis 1 (NF1) is characterized by multiple cafe-au-lait spots and neurofibromas on or under the skin. There can also be freckles in the armpits and groin areas, and small benign growths on the iris (the colored part of the eye). Less commonly, deformities of the bones and spine may also occur, as well as abnormalities of the blood vessels. Occasionally, tumors may develop in the brain, on cranial nerves, or on the spinal cord. About 50-60% of people with NF1 have learning disabilities, which may include verbal and non-verbal learning disorders, ADHD, and problems with coordination and speech. 

NF1 is a relatively common genetic condition; it affects 1 in every 3,000 babies and over 100,000 Americans.  It is usually diagnosed sometime in childhood.  Most people with NF1 are mildly affected, but about 20% have significant problems, including more than one body system.  The course of NF1 is unpredictable, and varies from one individual to another.

Diagnosis
The diagnosis of neurofibromatosis does not require genetic testing. It is made clinically, based on having two or more of the following features:

  1. Six or more cafe-au-lait spots 

  2. Two or more neurofibromas or a plexiform neurofibroma 

  3. Freckles in the areas of the armpit or the groin 

  4. An optic glioma (a tumor of the optic nerve) 

  5. Lisch nodules  ("freckles" on the iris of the eye) 

  6.  Sphenoid dysplasia or tibial dysplasia (A specific kind of bone problem)

  7.  A parent, child, brother, or sister with NF1

Cause
NF1 is caused by a change (mutation) in a specific gene called NF1, located on chromosome 17.

Inheritance
Neurofibromatosis, type 1 is inherited in an autosomal dominant pattern. In general, "autosomal dominant" means that the condition occurs equally in males and females, and that there is a 50% chance for the gene to be passed to a child. Therefore, individuals who have a diagnosis of NF1, have a 50% chance (in each pregnancy) to have a child with the same condition.

NF1 can sometimes happen for the first time in a family because of a new genetic change, also called a "spontaneous mutation". This random change happens when the sperm or egg cell is being formed. In these families, neither parent is affected. This happens in about half of all NF cases.

Treatment/Services
Most people with NF1 do very well, and do not have significant medical problems.  No one can predict which children with NF1 will develop problems, or which problems they will have. Because every case of NF1 is different, treatment must be determined on a case-by-case basis, depending on which symptoms are present. Although there is no cure for NF, treatments and therapies can address some of the problems that may arise.

  • Eyes/Vision:  It is important for children with NF1 to have a yearly check-up with a pediatrician, and a yearly eye exam by an Ophthalmologist.  Visits to a specialist may also be necessary. About 10% or people with NF1 have a thickening or tumor of the optic nerve, the nerve that connect the eyes to the brain. Since optic gliomas can impair vision, children with NF1 should see an ophthalmologist yearly. Chemotherapy or surgery may be an option for some children with optic glioma if vision is threatened.  However, most optic gliomas are just routinely monitored, and do not need treatment.

  • Skin:  Neurofibromas on the skin may be removed by a plastic surgeon or dermatologist, but it is possible they may grow back. If a neurofibroma develops in a painful or inconvenient location, surgical reduction of the tumor may be possible. It may be difficult or impossible to remove a deep plexiform neurofibroma. 

  • Bones: A curve in the spine, called scoliosis, is more common in people who have NF1, so periodic X-rays and physical examinations are important. A spine fusion may be necessary if the scoliosis progresses rapidly. If defects of the bone are present, orthopedic surgery may be necessary. 

  • Learning: Because many people with NF1 have learning disabilities, special accommodations may be requested at school or work.  Evaluation by a neuropsychologist can be useful in determining whether a person suffers from a learning disability and what type of learning issues are present.

  • Speech and coordination: Difficulty with speech can occur with NF1, and ADHD is more common in those who have NF1.  People with NF1 may be less coordinated in physical activity and skills such as handwriting.  Specific therapies, such as speech therapy, physical therapy, and occupational therapy, can be helpful in dealing with these issues.

  • Blood Pressure: Routine blood pressure checks are necessary for all individuals with NF1 to detect hypertension and problems with blood vessels.