Neurofibromatosis Classification and external resources |
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Back of an elderly woman with Neurofibromatosis. | |
ICD-10 | Q85.0 |
ICD-9 | 237.7 |
ICD-O: | 9540/0 |
eMedicine | derm/287 |
MeSH | D017253 |
Neurofibromatosis is a genetically-inherited 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. [1]
Neurofibromatosis is autosomal dominant, which means that it affects males and females equally and is 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.
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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:
Neurofibromatosis type 2 - mutation of merlin chromosome 22q12
Schwannomatosis - gene involved has yet to be identified
One must keep in mind, however, that neurofibromatosis can't occur in or affect any 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.
Neurofibromatosis type 1 is due to mutation on chromosome 17q11.2 , the gene product being Neurofibromin ( a GTPase activating enzyme).[2]
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.[3] 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.[4]
Neurofibromatosis affects humans on a genetic level, meaning that it either destroys, or renders defective a specific gene. NF-1
People with Neurofibromatosis can be affected in many different ways.
Because there is no cure for the disease itself, the only therapy for people with neurofibromatosis is a program of treatment 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 may be successful.[5]
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.[6]
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.
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.
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.
In November 2006, there was an hour-long documentary on the British television network Channel 4 about Facing the World, an organization that helps children with severe facial disfigurements in developing countries. One of the children featured on the documentary was Arianto, an Indonesian boy who suffered from a severe form of neurofibroma resulting in hemifacial giganticism.
In January 2008, 32-year-old Huang Chuncai of China underwent a second operation to remove another 4.5 kg (9.9 lb) of tumor from his face. A previous operation removed 15 kg (33 lb) from what was originally a 23 kg (55.7 lb) tumor. [7] [8]
In March 2008 the treatment of 30-year-old neurofibromatosis victim Pascal Coler of France ended after having received what his doctors call the world's first successful full face transplant.[9][10]
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