Many children with NF1 have larger than normal head circumference and are shorter than average. Hydrocephalus, the abnormal buildup of fluid in the brain, is a possible complication of the disorder. Headache and epilepsy are also more likely in individuals with NF1 than in the healthy population. Cardiovascular complications associated with NF1 include congenital heart defects, high blood pressure (hypertension), and constricted, blocked, or damaged blood vessels (vasculopathy). Children with NF1 may have poor language and visual-spatial skills, and perform less well on academic achievement tests, including those that measure reading, spelling, and math skills. Learning disabilities, such as attention deficit hyperactivity disorder (ADHD), are common in children with NF1. An estimated 3 to 5 percent of tumors may become cancerous, requiring aggressive treatment. These tumors are called malignant peripheral nerve sheath tumors.
To diagnose NF1, a doctor looks for two or more of the following:
- six or more light brown spots on the skin (often called “café-au-lait” spots), measuring more than 5 millimeters in diameter 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 (called an optic nerve 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 with NF1
NF1 is the most common neurofibromatosis, occurring in 1 in 3,000 to 4,000 individuals in the United States. Although many affected people inherit the disorder, between 30 and 50 percent of new cases result from a spontaneous genetic mutation of unknown cause. Once this mutation has taken place, the mutant gene can be passed to succeeding generations.
Why these tumors occur still isn’t completely known, but it appears to be related mainly to mutations in genes that play key roles in suppressing cell growth in the nervous system. These mutations keep the genes—identified as NF1, NF2 and SMARCB1/INI1—from making normal proteins that control cell production. Without the normal function of these proteins, cells multiply out of control and form tumors.
The most common nerve-associated tumors in NF1 are neurofibromas (tumors of the peripheral nerves), whereas schwannomas (tumors that begin in Schwann cells that help form the myelin sheath) are most common in NF2 and schwannomatosis. Most tumors are benign, although occasionally they may become cancerous.