Neurofibromatosis

s as seen in NF1 Neurofibromatosis type 1 in early life may cause learning and behavior problems – about 60% of children who have NF1 have mild difficulty in school. Signs the individual might have are as follows: • Six or more light brown dermatological spots ("café au lait spots") • At least two neurofibromas • At least two growths on the eye's iris • Abnormal growth of the spine (scoliosis) • Lisch nodules • Tumors on the adrenal glands called pheochromocytomas People with neurofibromatosis type 2 can exhibit the same type of skin symptoms as type 1, but not necessarily in every case. Symptoms may include pain due to pressure on nerves, tinnitus, weakness in fingers, numbness, headaches. The symptom most characteristic of NF2 is hearing loss. The hearing loss occurs due to the pressure of tumors on the acoustic nerve. The same pressure can cause headaches, dizziness, and nausea. ==Cause==

The three types of neurofibromatosis are caused by different mutations on chromosomes. NF1 is caused by a mutation on the NF1 gene on the arm of chromosome 17. The types of neurofibromatosis are: • Neurofibromatosis type I, in which the nerve tissue grows tumors (neurofibromas) that may be benign, but may cause serious damage by compressing nerves and other tissues. • Neurofibromatosis type II, in which bilateral acoustic neuromas (tumors of the vestibulocochlear nerve or cranial nerve 8 (CN VIII) also known as schwannoma) develop, often leading to hearing loss. • Schwannomatosis, in which painful schwannomas develop on spinal and peripheral nerves. ==Pathophysiology==

The pathophysiology is varied, and each NF type has a different one: • Neurofibromatosis type I is the most common of the three types and is caused by genetic changes in the NF1 gene located on chromosome 17 (17q11.2). This gene encodes a cytoplasmic protein known the neurofibromin, which functions as a tumor suppressor and therefore serves as a signal regulator of cell proliferation and differentiation. A dysfunction or lack of neurofibromin can affect regulation, and cause uncontrolled cell proliferation, leading to the tumors (neurofibromas) that characterize NF1. 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. The mutation falls on the NF2 tumor suppressor 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. ==Diagnosis==

The neurofibromatoses are considered as RASopathies and as members of the neurocutaneous syndromes (phakomatoses). The diagnosis of neurofibromatosis is done via the following means: Differential diagnosis Conditions similar to NF include: ==Treatment==

Surgical removal of tumors is an option; however, the risks involved should be assessed first. With regard to OPG (optic pathway gliomas), the preferred treatment is chemotherapy. However, radiotherapy is not recommended in children who present with this disorder. It is recommended that children diagnosed with NF1 at an early age have an examination each year, which allows any potential growths or changes related to the disorder to be monitored. ==Prognosis==

, a British actor with neurofibromatosis In most cases, symptoms of NF1 are mild, and individuals live normal and productive lives. In some cases, however, NF1 can be severely debilitating and may cause cosmetic and psychological issues. The course of NF2 varies greatly among individuals. In some cases of NF2, the damage to nearby vital structures, such as other cranial nerves and the brain stem, can be life-threatening. Most individuals with schwannomatosis have significant pain. In some extreme cases, the pain will be severe and disabling. ==Epidemiology==

In the United States, about 1 in 3,500 people have NF1, 1 in 25,000 have NF2, and 1 in 40,000 have schwannomatosis. Males and females are affected equally often in all three conditions. In NF1, symptoms are often present at birth or develop before 10 years of age. While the condition typically worsens with time, most people with NF1 have a normal life expectancy. In NF2, symptoms may not become apparent until early adulthood. NF2 increases the risk of early death. Schwannomatosis symptoms develop in early childhood and can worsen with time. Typically life expectancy is unaffected in those with schwannomatosis. ==History==

Descriptions of what is believed to be the condition go as far back as the 1st century. The conditions were formally described by Friedrich Daniel von Recklinghausen in 1882, after whom it was previously named. == References ==