Neurofibromatosis

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Neurofibromatosis is a genetically-transmitted disease in which nerve cells (Schwann cells) grow tumors (neurofibromas) that may be harmless or may cause serious damage by compressing nerves and other tissues. The tumors may cause bumps under the skin, colored spots, skeletal problems, pressure on spinal nerve roots, and other neurological problems. ^[1] The disease occurs in approximately one in every 3,000 children. ^{[2] [3]}

Neurofibromatosis is inherited through a dominant gene. That means that if a child gets one gene for neurofibromatosis from one parent, and a normal gene from the other parent, that child will have neurofibromatosis. 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 incomplete penetrance).

[edit] 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.^[4]

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 or perhaps a combination of the two conditions. This however has given rise to the common misconception that Neurofibromatosis and "Elephant Man Disease" are one and the same.

[edit] Types

• Neurofibromatosis type II (or "MISME Syndrome"). Incidence is 1:40,000.

• Five other, extremely rare, forms are also recognized:
  • Online 'Mendelian Inheritance in Man' (OMIM) 162210 - NEUROFIBROMATOSIS, FAMILIAL SPINAL
  • Online 'Mendelian Inheritance in Man' (OMIM) 162220 - NEUROFIBROMATOSIS, FAMILIAL INTESTINAL; NF3B
  • Online 'Mendelian Inheritance in Man' (OMIM) 162240 - NEUROFIBROMATOSIS-PHEOCHROMOCYTOMA-DUODENAL CARCINOID SYNDROME
  • Online 'Mendelian Inheritance in Man' (OMIM) 162260 - NEUROFIBROMATOSIS, TYPE III, MIXED CENTRAL AND PERIPHERAL; NF3A
  • Online 'Mendelian Inheritance in Man' (OMIM) 601321 - NEUROFIBROMATOSIS-NOONAN SYNDROME; NFNS

[edit] Symptoms

[edit] Neurofibromatosis type 1

Neurofibromatosis type 1 - mutation of neurofibromin chromosome 17q11.2

• Multiple neurofibromas on the skin and under the skin; the subcutaneous lumps are characteristic of the disease and increase in number with age.
• Freckling of the groin and the arm pit.
• A predisposition to particular tumors (both benign and malignant). These tumors are called neurofibromas.
• Café au lait spots (pigmented birthmarks). Six or more of these form one of the diagnostic criteria, but are not essential for diagnosis.
• Skeletal abnormalities such as scoliosis or bowing of the legs might occur
• Lisch nodules (hamartomas of iris)
• Tumor on the optic nerve, also known as an Optic Glioma

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

[edit] Neurofibromatosis type 2

Neurofibromatosis type 2 - mutation of merlin chromosome 22q12

• bilateral tumors, acoustic neuromas on the vestibulocochlear nerve
• 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

[edit] Schwannomatosis

Schwannomatosis - gene involved has yet to be identified

1. Multiple Schwannomas occur.
2. The Schwannomas develop on cranial, spinal and peripheral nerves.
3. Chronic pain, and sometimes numbness, tingling and weakness.
4. 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.
5. 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.
6. Patients with Schwannomatosis do not have learning disabilities related to the disease.

[edit] 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).^[5]

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.^[6] 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 spontaneously through random mutation, with no family history. These spontaneous or sporadic cases account for about one half of neurofibromatosis cases (ibid).

[edit] Family

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.

[edit] 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.

[edit] Notable Cases

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 9.9 lb (4.5 kg) of tumor from his face. A previous operation removed 33 pounds (15 kg) from what was originally a 55.7 lb (23 kg) 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 worlds first successful full face transplant.^[9][10]

[edit] See also

Wikinews has related news:

Interview with Reggie Bibbs on his life with neurofibromatosis

• Neurofibroma

[edit] References

[edit] External links

• Information page from the National Institute of Neurological Disorders and Stroke (part of the National Institutes of Health in the United States) -- this Wikipedia article is based largely on this NINDS information page
• Vestibular Schwannoma (Acoustic Neuroma) and Neurofibromatosis at National Institute on Deafness and Other Communication Disorders
• "Just Ask" Campaign encourages informative outreach. The story of Reggie Bibbs.
• NEUROFIBROMATOSIS from the National Center for Biotechnology Information
• Neurofibromatosis at the Open Directory Project
• [1]