Neurofibromatosis

Neurofibromatosis is an autosomal dominant genetic disorder. It encompasses a set of distinct genetic disorders that cause tumors to grow along types of nerves and, in addition, can affect the development of non-nervous tissues such as bones and skin. The tumors can grow anywhere on or in the body. Incidence is 1:3,000.

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History

Neurofibromatosis was discovered in 1882 by 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 or perhaps a combination of the two conditions.

Types

Apart from the common form, there are two rarer forms and several even rarer forms:

• Neurofibromatosis type I (was known as Von Recklinghausen disease after Friedrich Daniel von Recklinghausen). Incidence is 1:3500.

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

• Schwannomatosis is a rare form that is clinically and genetically distinct from types I and II. Multiple Schwannomas (rather than Neurofibromas) occur, and about one-third of patients have these tumors in only one part of the body. Incidence is 1:40,000. The vestibular nerve is spared. Pain is the primary symptom, although numbness, tingling and weakness can also occur. Schwannomas are always benign.

• Six other, extremely rare, forms are also recognized:
  • Online 'Mendelian Inheritance in Man' (OMIM) 162210
  • Online 'Mendelian Inheritance in Man' (OMIM) 162220
  • Online 'Mendelian Inheritance in Man' (OMIM) 162240
  • Online 'Mendelian Inheritance in Man' (OMIM) 162260
  • Online 'Mendelian Inheritance in Man' (OMIM) 162270
  • Online 'Mendelian Inheritance in Man' (OMIM) 601321

Symptoms

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

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

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 forums 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.

Genetics and Hereditability

  Neurofibromatosis type 1 is due to mutation on chromosome 17q11.2 , the gene product being Neurofibromin ( a GTPase activating enzyme).^[1]

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 (Korf and Rubenstein 2005). 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).

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.

Neurofibromatosis in Pop Culture

In the television series Dallas, the inherited neurofibromatosis of the Barnes family is a driving plot device, though the portrayal of the condition does leave something to be desired in terms of scientific fact.

It has been mentioned as a possible diagnosis many times in the Fox drama House.

The disease is also a pivotal plot element in the Icelandic film Mýrin (Jar City) and the novel in which it was based.

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.

See also

• Neurofibroma

References

• Korf, Bruce E. and Allan E. Rubenstein. 2005. Neurofibromatosis: A Handbook for Patients, Families, and Health Care Professionals.

Charities

• Neurofibromatosis, Inc. (of the United States)
• Children's Tumor Foundation - Formerly: The National Neurofibromatosis Foundation (United States)
• Texas Neurofibromatosis Foundation
• NF Cure Project
• Neurofibromatosis, Inc. of New England, U.S.
• Neurofibromatosis, Inc. of Mid-Atlantic, U.S.
• NFMalaysia.org
• Neurofibromatosis Association - UK based
• Home Page - A support group for people with NF2 and their families.
• The British Columbia Neurofibromatosis Foundation
• The NF Society of Ontario
• The Neurofibromatosis Association of Australia