What's neurofibromatosis type 1 (NF1)?Neurofibromatosis 1, also known as von Recklinghausen neurofibromatosis, is one of the most frequent dominant disorders in man, affecting ~1 in 3,000 births. A hallmark of NF1 is its variability of symptoms, which include abnormally pigmented skin patches (cafe-au-lait spots), iris hamartomas (Lisch nodules), and benign neurofibromas (peripheral nerve tumors consisting mainly of Schwann cells with fibroblasts, mast cells, and other cellular elements) that may be profoundly
disfiguring. About 5% of NF1 patients develop malignant peripheral nerve sheath tumors (malignant neurofibrosarcomas) that are often fatal. NF1 patients show increased risk for several other tumors, such as optic gliomas, astrocytomas and juvenile malignant myeloid disorders, making it a familial cancer syndrome. Other frequent features of NF1 are learning disabilities and skeletal abnormalities. NF1 is caused by inactivating mutations in a tumor suppressor gene on chromosome 17q which encodes neurofibromin, a large protein with a RasGTPase activating domain that implicates it as a regulator of signal transduction.
Neurofibromatosis type 1 is inherited in an autosomal dominant manner and is due to mutation of the NF1 gene (in chromosome band 17q11) that encodes a protein called neurofibromin. NF1 is characterized by a number of remarkable skin findings including multiple café au lait (coffee with milk) spots, multiple benign tumors called neurofibromas on the skin, plexiform neurofibromas (thick and misshapen nerves due to the abnormal growth of cells and tissues that cover the nerve), and freckles in the armpit and groin. The café au lait spots increase in number and size with age. Ninety-seven percent of people with NF1 have 6 or more café au lait spots by age 20. The skin neurofibromas appear later, usually in the second decade of life. In NF1 there is an increased risk of scoliosis, optic gliomas (benign tumors on the optic nerve), epilepsy, and learning disability. The risk of malignant degeneration of neurofibromas is below 5 percent.