Neurofibromatosis type 1 (NF1) is a genetic condition that causes tumors to grow along nerves in the skin, brain, and other parts of the body. It is a multisystem disorder characterized by multiple café au lait macules, intertriginous freckling, multiple cutaneous neurofibromas, and iris Lisch nodules. The severity of the condition can vary considerably from person to person. NF1 is usually diagnosed during childhood, and signs are often noticeable at birth or shortly afterward and almost always by age 10. Symptoms of NF1 include:
- Flat, light brown spots on the skin (cafe au lait spots)
- Soft, non-cancerous tumors on or under the skin (neurofibromas)
- Clusters of freckles in unusual places – such as the armpits, groin, and under the breast
- Problems with the bones, eyes, and nervous system
- Learning difficulties
- Macrocephaly (an unusually large head)
- Headache
- Glaucoma
- Numbness or weakness
- Pain
- Seizures
- Problems with self-image
- Anxiety
- Attention-deficit/hyperactivity disorder (ADHD) and learning disabilities (affecting about 65% of people with NF1)
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. Less commonly, NF1 is associated with a type of cancer known as malignant peripheral nerve sheath tumors. NF1 is caused by mutations in the NF1 gene, which 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. NF1 is considered to have an autosomal dominant pattern of inheritance, and people with this condition are born with one mutated copy of the NF1 gene in each cell.
