Neurofibromatosis Type 1

Neurofibromatosis type 1 (NF1) is a genetic condition in which benign tumors arise along nerves anywhere in the body. Treatment for these tumors most often includes surgery; it sometimes also includes chemotherapy, radiation therapy, or both.

NF1 is the most common of a group of genetic conditions collectively called neurofibromatosis. The other conditions in this group are neurofibromatosis type 2 (NF2) and schwannomatosis. Neurofibromatosis is part of a broad category of neurological disorders called neurocutaneous syndromes.

NF1 causes small, benign tumors called neurofibromas that grow along nerves or under the skin and manifest as small bumps underneath the skin. These tumors typically do not arise until adolescence or adulthood.

When neurofibromas span long sections along nerves, they are called plexiform neurofibromas. About half of individuals with NF1 develop plexiform neurofibromas. Although benign, plexiform neurofibromas can grow large and cause significant pain and problems due to their compression of nearby nerves. These tumors can later become more aggressive, converting to malignant peripheral nerve sheath tumors.

Individuals with NF1 may also develop tumors in other locations, including tumors of the brain and spine. Possible brain tumors include gangliomas, optic gliomas, juvenile pilocytic astrocytomas, and brainstem gliomas. Optic gliomas are the most common.


Symptoms can vary from patient to patient and often become evident as a child ages.

The initial characteristic sign of NF1 is a change in skin pigmentation. This occurs among young children and manifests as café-au-lait spots, which are areas on the skin that are darker than the surrounding skin. The number of café-au-lait spots increases as the child ages, and freckles may also develop under the arms or around the groin.

Other common symptoms include hypertension, short stature, macrocephaly, and lisch nodules. Bone abnormalities, such as bowing of the tibia and fibula or scoliosis, may occur.

Most individuals with NF1 have normal intelligence, but some may have learning disabilities.


A diagnosis can usually be made in the clinic by acquiring a medical history and performing a physical examination. In addition, a neurological examination may be conducted to seek neurofibromas and any brain tumors. This exam consists of evaluating swallowing, hearing, sense of smell, eye movements, sensation, motor function, balance, and coordination. Also, an eye exam may be performed to evaluate eye health and determine any problems.

Imaging studies add detail to physicians’ understanding of an individual patient’s neurofibromas and the brain tumors that may accompany NF1. Computed tomography (CT) scans or magnetic resonance imaging (MRI) scans can be used to visualize the tumors. CT and MRI scans can be conducted with or without contrast enhancement.

To confirm the diagnosis, a tissue biopsy must be performed.

Although NF1 can usually be diagnosed during a visit with a physician, genetic testing of a blood sample may be helpful for confirmation.

Risk Factors

NF1 is caused by a mutation in the NF1 gene, a tumor suppressor important to many cells in the nervous system. About half of individuals develop NF1 by inheriting a non-working copy of NF1 from a parent who has NF1. (The other parent contributes a working copy of the gene.) The other half of individuals do not have a family history of this disease; instead, they acquire a spontaneous mutation in one copy of NF1 at conception that renders it non-working.

Although the disease is present at birth, a diagnosis may not be made until a child is older and symptoms are evident.

The inheritance of NF1 follows an autosomal dominant pattern, which means that if a parent has NF1, there is a 50 percent chance that each of his or her offspring will have NF1.

Tumors associated with NF1 develop in certain cells, most commonly specialized cells that surround nerves, when the single working copy of the NF1 tumor suppressor gene in one of these cells acquires a spontaneous mutation. Spontaneous mutations are not uncommon. They go unnoticed in the gene NF1 when a working copy of the gene is available as backup. But when only one working copy of NF1 is present, and it acquires a spontaneous mutation, no working copies of the tumor suppressor gene remain in that cell. A tumor begins to form.


At Columbia, our neurosurgeons use the most sophisticated techniques to treat neurofibromas and other tumors that accompany NF1, resulting in the best possible outcomes.

For neurofibromas and most plexiform neurofibromas, surgery can be performed meticulously to resect the tumor away from the delicate nerve, leaving the nerve intact and function preserved. Some larger plexiform neurofibromas may not be amenable to surgery if their resection would require the removal of nerve tissue and result in loss of nerve function. Instead, radiation therapy, chemotherapy, or both may be used for these large tumors.

Treatment for brain tumors that are associated with NF1 depends on the characteristics of the tumor and the tumor location. Typically, treatment involves a combination of brain tumor surgery to resect the tumor, and radiation therapy or chemotherapy.