Neurofibromatosis 1 week ago
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
 Diagnostic Criteria
 Neurofibromatosis type 1
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.
bilateral tumors, acoustic neuromas on the vestibulocochlear nerve, located on the eighth cranial nerve leading to hearing loss
Multiple Schwannomas occur.
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
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.
 How NF Can Affect You
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.
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 in Pop Culture
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