Neurofibromatosis type I (NF-1) is a complex multi-system human disorder caused by the mutation of neurofibromin, a gene on chromosome 17 that is responsible for production of a protein which is needed for normal function in many human cell types. NF-1 causes tumors along the nervous system which can grow anywhere on the body. NF-1 is one of the most common genetic disorders and is not limited to any persons race or sex. NF-1 is an autosomal dominant disorder, which means that mutation or deletion of one copy (or allele) of the NF-1 gene is sufficient for the development of NF-1, although presentation varies widely and is often different even between relatives affected by NF-1.As of 2015, there are at least 100,000 people in the U.S. and about 10,000 people in the UK who have been diagnosed with NF. Common symptoms of NF-1 include brownish-red spots in the colored part of the eye called Lisch nodules, benign skin tumors called neurofibromas, and larger benign tumors of nerves called plexiform neurofibromas, scoliosis (curvature of the spine), learning disabilities, vision disorders, mental disabilities, multiple café au lait spots and epilepsy. NF-1 affected individuals also have a much higher rate of cancer and cardiovascular disease than the population in general.NF-1 is a developmental syndrome caused by germline mutations in neurofibromin, a gene that is involved in the RAS pathway (RASopathy).
There is practical flowchart to distinguish between NF1, NF2 and schwannomatosis. Six or more café-au-lait spots over 5 mm in greatest diameter in pre-pubertal individuals and over 15 mm in greatest diameter in post-pubertal individuals. Note that multiple café-au-lait spots alone are not a definitive diagnosis of NF-1 as these spots can be caused by a number of other conditions. Two or more neurofibromas of any type or 1 plexiform neurofibroma
Freckling in the axillary (Crowe sign) or inguinal regions
Optic nerve glioma
Two or more Lisch nodules (pigmented iris hamartomas)
A distinctive osseous lesion such as sphenoid dysplasia, or thinning of the long bone cortex with or without pseudarthrosis. A first degree relative (parent, sibling, or offspring) with NF-1 by the above criteria. Treatment
Selumetinib, sold under the brand name Koselugo, is a drug approved by FDA in April 2020 for the treatment of NF-1 in pediatric population who are two or more years of age. It is a kinase inhibitor and is indicated for use pediatric patients who are symptomatic and have plexiform neurofibromas which cannot be operated.There is no cure for the disorder itself. Instead, people with neurofibromatosis are followed by a team of specialists to manage symptoms or complications. In progress and recently concluded medical studies on NF-1 can be found by searching the official website of the National Institutes of Health. Prognosis
NF-1 is a progressive and diverse condition, making the prognosis difficult to predict. The NF-1 gene mutations manifest the disorder differently even amongst people of the same family. This phenomenon is called variable expressivity.