Neurofibromatosis is a genetically-transmitted disease in which nerve tissue grows tumors (e.g. neurofibromas) that may be harmless or may cause serious damage by compressing nerves and other tissues. The disorder affects all neural crest cells (Schwann cells, melanocytes, endoneurial fibroblasts). Cellular elements from these cell types proliferate excessively throughout the body forming tumors and the melanocytes function abnormally resulting in disordered skin pigmentation.The tumors may cause bumps under the skin, colored spots, skeletal problems, pressure on spinal nerve roots, and other neurological problems. Types Neurofibromatosis type I Incidence is 1:3,000 Neurofibromatosis type II (or “MISME Syndrome”). Incidence is 1:25,000 Schwannomatosis. Incidence is unknown but thought to be 1:40,000
 Diagnostic Criteria
 Neurofibromatosis type 1 Neurofibromatosis type 1 – mutation of neurofibromin chromosome 17q11.2. The diagnosis of NF1 is made if any two of the following seven criteria are met:
Two or more neurofibromas on the skin or under the skin or one plexiform neurofibroma (a large cluster of tumors involving multiple nerves); Neurofibromas are the subcutaneous lumps that are characteristic of the disease and increase in number with age. Freckling of the groin or the axilla (arm pit). Café au lait spots (pigmented birthmarks). Six or more measuring 5 mm in greatest diameter in prepubertal individuals and over 15 mm in greatest diameter in postpubertal individuals Skeletal abnormalities, such as sphenoid dysplasia or thinning of the cortex of the long bones of the body (i.e. bones of the leg, potentially resulting in bowing of the legs) Lisch nodules (hamartomas of iris), freckling in the iris. Tumors on the optic nerve, also known as an optic glioma A first-degree relative with a diagnosis of NF1
plexiform neurofibroma Patient with multiple small cutaneous neurofibromas and a ‘café au lait spot’ (bottom of photo, to the right of centre). A biopsy has been taken of one of the lesions  Neurofibromatosis type 2 Neurofibromatosis type 2 – mutation of merlin chromosome 22q12
bilateral tumors, acoustic neuromas on the vestibulocochlear nerve, located on the eighth cranial nerve leading to hearing loss In fact, the hallmark of NF 2 is hearing loss due to acoustic neuromas around the age of twenty the tumors may cause: headache balance problems, and Vertigo facial weakness/paralysis patients with NF2 may also develop other brain tumors, as well as spinal tumors Deafness and Tinnitus Any relative with NF-2, diagnosed or not
 Schwannomatosis Schwannomatosis – gene involved has yet to be identified
Multiple Schwannomas occur. The Schwannomas develop on cranial, spinal and peripheral nerves. Chronic pain, and sometimes numbness, tingling and weakness. About 1/3 of patients have segmental Schwannomatosis, which means that the Schwannomas are limited to a single part of the body, such as an arm, a leg or the spine. Unlike the other forms of NF, the Schwannomas do not develop on vestibular nerves, and as a result, no loss of hearing is associated with Schwannomatosis. Patients with Schwannomatosis do not have learning disabilities related to the disease.
One must keep in mind, however, that neurofibromatosis can occur in and affect nearly all of the organ systems, whether that entails simply compressing them (from tumor growth) or in fact altering the organs in some fundamental way. This disparity in the disease is one of many factors that makes it difficult to diagnose, and eventually find a prognosis for.
 Genetics and Hereditability
NF-1 and NF-2 may be inherited in an autosomal dominant fashion, as well as through random mutation.Neurofibromatosis type 1 is due to mutation on chromosome 17q11.2 , the gene product being Neurofibromin ( a GTPase activating enzyme).
Neurofibromatosis type 2 is due to mutation on chromosome 22q , the gene product is Merlin, a cytoskeletal protein.
Both NF1 and NF2 are autosomal dominant disorders, meaning that only one copy of the mutated gene need be inherited to pass the disorder. A child of a parent with NF1 or NF2 and an unaffected parent will have a 50% chance of inheriting the disorder.
Complicating the question of heritability is the distinction between genotype and phenotype, that is, between the genetics and the actual manifestation of the disorder. In the case of NF1, no clear links between genotype and phenotype have been found, and the severity and specific nature of the symptoms may vary widely among family members with the disorder. In the case of NF2, however, manifestations are similar among family members; a strong genotype-phenotype correlation is believed to exist (ibid).
Both NF1 and NF2 can also appear to be spontaneous mutation, with no family history. These cases account for about one half of neurofibromatosis cases (ibid).
Similar to polydactyly, although NF is a dominant mutation, it is not prevalent in society. Neurofibromatosis-1 is found in approximately 1 in 2,500-3,000 live births (carrier incidence 0.0004, gene frequency 0.0002). NF-2 is less common, having one case in 50,000-120,000 live births.
 How It Works Neurofibromatosis affects humans on a genetic level, meaning that it either destroys, or renders defective a specific gene. NF-1
The gene that NF-1 affects is large, on band 17q11.2. It encodes for a protein called neurofibromin, otherwise known as “the tumor suppressor” protein. Neurofibromatosis alters or weakens this protein, rapid, radical growth of cells is allowed all over the body, especially around the nervous system. This leads to the normal symptoms for neurofibromatosis – clumpings of these tumors, called neurofibromas and schwannomas. Less is known about the NF-2 linked gene. However, it is on band 22q1 and also codes for a protein, most likely one similar to NF-1’s.
 How NF Can Affect You People with Neurofibromatosis can be affected in many different ways.
There is a high incidence of learning disabilities in people with NF. It is believed that at least 50% of people with NF have learning disabilities of some type. increased chances of development of petit mal epilepsy (a Partial absence seizure disorder) The tumors that occur can grow anywhere a nerve is present. This means that: They can grow in places that are very visible to people that a patient may encounter on the street. The tumors can also grow in places that can cause other medical issues that may require them to be removed for the patient’s safety. Affected individuals may need multiple surgeries, depending on where the tumors are located.
 Treatment There is no cure for the disease itself. Instead, people with neurofibromatosis are followed by a team of specialists to manage symptoms or complications. Surgery may be needed when the tumors compress organs or other structures. Less than 10% people with neurofibromatosis develop cancerous growths; in these cases, chemotherapy can be tried.
 History Neurofibromatosis was discovered in 1882 by the German pathologist Friedrich Daniel von Recklinghausen. He wrote on it and published it in Hämochromatose, Tageblatt der Naturforschenden Versammlung.
Joseph Merrick, the Elephant Man, was once considered to have been afflicted with either elephantiasis or neurofibromatosis type I. However, it is now generally believed that Merrick suffered from the very rare Proteus syndrome. This however has given rise to the common misconception that Neurofibromatosis and “Elephant Man Disease” are one and the same.
 Related disorders Neurofibromatosis is considered a member of the neurocutaneous syndromes (phakomatoses). In addition to the types of neurofibromatosis, the phakomatoses also include tuberous sclerosis, Sturge-Weber syndrome and von Hippel-Lindau disease. This grouping is an artifact of an earlier time in medicine, before the distinct genetic basis of each of these diseases was understood.
 Neurofibromatosis in Pop Culture In the television series Dallas, the inherited neurofibromatosis of the Barnes family is a driving plot device, although the portrayal of the condition does leave something to be desired in terms of scientific fact.
The disease is also a pivotal plot element in the Icelandic film Mýrin (Jar City) and Tainted Blood, the novel on which it was based.
Gillian Anderson, who played Scully on the X-Files, is a spokesperson and helps in the raising of money for neurofibromatosis, because her brother suffers from the disease
Neurofibromatosis is autosomal dominant, which means that it is autosomal (it affects males and females equally often) and dominant (only one copy of the affected gene is needed to get the disorder). Therefore, if only one parent has neurofibromatosis, his or her children have a 50% chance of developing the condition as well. Disease severity in affected individuals, however, can vary (this is called variable expressivity). Moreover, in around half of cases there is no other affected family member because a new mutation has occurred