Neurofibromatosis Type 1 (NF1)

This information is provided by the National Organization for Rare Disorders (NORD). 


Neurofibromatosis 1 (NF1), also called von Recklinghausen’s disease, is a genetic disorder characterized by the development of multiple noncancerous (benign) tumors of nerves and skin (neurofibromas) and areas of abnormal skin color (pigmentation). Areas of abnormal skin pigmentation typically include pale tan or light brown discolorations (cafe-au-lait spots), freckling in atypical locations such as under the arms (axillary region) or in the groin (inguinal region). Such abnormalities of skin pigmentation are often evident by one year of age and tend to increase in size and number over time.

At birth or early childhood, affected individuals may have relatively large, benign tumors that consist of bundles of nerves and other tissue (plexiform neurofibromas). Individuals with NF1 may also develop benign nodules on the colored regions of the eyes (Lisch nodules), or tumors in the nerves of the visual pathway (optic pathway gliomas). More rarely, affected individuals may develop certain malignant (cancerous) tumors.

NF1 may also be characterized by an unusually large head size (macrocephaly) and relatively short stature. Additional abnormalities may also be present, such as episodes of uncontrolled electrical activity in the brain (seizures); learning disabilities, and attention deficits; speech difficulties; abnormally increased activity (hyperactivity); and skeletal malformations, including progressive curvature of the spine (scoliosis), bowing of the lower legs (pseudoarthrosis), and improper development of certain bones. Associated symptoms and findings may vary greatly in range and severity from person to person, even within the same family. Most people with NF1 have normal intelligence but learning disabilities appear in about 50% of children with NF1.

NF1 is caused by changes (mutations) in a gene called NF1, which is found on chromosome 17. This gene regulates the production of a protein known as neurofibromin, which is thought to function as a tumor suppressor. In about 50 percent of individuals with NF1, the disorder results from spontaneous (sporadic) mutations of the gene that occur for unknown reasons. Such individuals do not inherit NF1 from their parents, but rather they are the first in their family with the disorder. In others, NF1 is inherited as an autosomal dominant trait.