The neurofibromas caused by NF consist of Schwann cells, fibroblasts, perineuronal cells, mast cells and axons embedded in an extracellular matrix. Another function of neurofibromin is to bind to microtubules that play a role in the release of adenylyl cyclase and its activity. Adenylyl cyclase plays an essential role in cognition. Neurofibromins role in the activity of adenylyl cyclase explains why patients with NF experience cognitive impairment.Neurofibromatosis type II is caused by a mutation on chromosome 22. The mutation falls on the NF2 tumor suppressor gene. The gene normally encodes a cytoplasmic protein known as merlin. The normal function of merlin is to regulate the activity of multiple growth factors, the mutated copy of the gene leads to merlins loss of function. The loss of function leads to increased activity of growth factors normally regulated by merlin, leading to the formation of the tumors associated with NF2.Schwannomatosis is caused by a mutation on the SMARCB1 gene. This gene is located near the NF2 tumor suppressor gene leading to the thought that schwannomatosis and NF2 were the same condition. The two conditions show different mutations on two different genes. The normal function of the SMARCB1 gene is to encode a protein called SMARCB1 that is part of a larger protein complex whose function is not completely understood. The complex including SMARCB1 plays a role in tumor suppression. The mutation of the SMARCB1 gene causes a loss of function in the complex leading to the formation of tumors indicative of schwannomatosis.
Neurofibromatosis (NF) is a group of three conditions in which tumors grow in the nervous system. The three types are neurofibromatosis type I (NF1), neurofibromatosis type II (NF2), and schwannomatosis. In NF1 symptoms include light brown spots on the skin, freckles in the armpit and groin, small bumps within nerves, and scoliosis. In NF2, there may be hearing loss, cataracts at a young age, balance problems, flesh colored skin flaps, and muscle wasting. In schwannomatosis there may be pain either in one location or in wide areas of the body. The tumors in NF are generally non-cancerous.The cause is a genetic mutation in certain oncogenes. These can be inherited from a persons parents, or in about half of cases spontaneously occur during early development. Different mutations result in the three types of NF. Neurofibromatosis arise from the supporting cells of the nervous system rather than the neurons themselves. In NF1, the tumors are neurofibromas (tumors of the peripheral nerves), while in NF2 and schwannomatosis tumors of Schwann cells are more common. Diagnosis is typically based on symptoms, examination, medical imaging, and biopsy. Genetic testing may rarely be done to support the diagnosis.There is no known prevention or cure. Surgery may be done to remove tumors that are causing problems or have become cancerous. Radiation and chemotherapy may also be used if cancer occurs.