Science Timeline

Last Updated: 03/28/17

Index

  1. Timeline
  2. Reference Sources

Related Topics

Neurofibromatosis (NF), initially called Von Recklinghausen disease, is not one but three separate genetic conditions that all result in the growth of tumors and neurological issues. The three diseases are called; Neurofibromatosis Type 1 (NF1), Neurofibromatosis Type 2 (NF2) and Neurofibromatosis Type 3 more commonly known as Schwannomatosis.

The history of NF is complicated and the development of genetic testing was needed for researchers to realize that there are in fact three forms, but this fact is not even commonly known today by all doctors since NF is rare and in some cases not even identified at all. The results are a common issue of inaccurate diagnosis of the wrong NF form and individuals not receiving the proper testing for treatments needed.

1. Timeline

  • 1820: NF Type 2 was first described by Dr. Wishart before the condition Von Recklinghausen disease was identified. [1]

  • 1830: Von Recklinghausen Neurofibromatosis Neurofibromatosis (NF1), was classified and confusion between the two in papers written and diagnosis started.[1]

  • 1882: NF was identified in literature by Dr. Friedrich Von Recklinghausen. NF was referred to as Von Recklinghausen's condition for some time and sometimes referred to when discussing NF1.[2]

  • 1977: First science laboratory use of a Magnetic Resonance Imaging (MRI).

  • 1979: Development of the first Auditory Brainstem Implant (ABI) started to make it possible for individuals with Bilateral VS nerve damage (hearing in neither ear) to have a chance at hearing. It was only a 2 Electrode Implant with very limited sound. This was not helpful enough it did not reach commercial use.

  • 1980: Commercial use of MRI started to become available for use on patients.

  • 1987: Mapping for genes for NF separated people with NF into 2 separate diseases while identified the location of NF1 on Chromosome 17 and NF2 on Chromosome 22[1]

  • 1987: General criteria for NF1 and NF2 was established.[3]
  • NF2 is characterized by Schwannoma of the 8th cranial nerve, specifically the Vestibular branch of the Nerve; these are typically called Vestibular Schwannoma or Acoustic Neuroma. Schwannoma can also be located on other cranial nerves, tumor types including; Meningiomas, Ependymomas but NF2 can also result in Ocular Manifestations.

  • 1988: Gadolinium-enhanced MRI made available for imaging, detection and diagnosis of Vestibular Schwannoma; lesions as small as 2mm are detectable.

  • 1990: Diagnostic criteria for NF2, any one of the following:[3]
    • Bilateral masses of the 8th Cranial Nerve;
    • 1 or more 1st degree relative with NF2 + unilateral vestibular mass of 8th cranial nerve;
    • 2 of the following: Neurofibroma, Meningioma, Glioma, Schwannoma, Juvenile Posterior Subcapsular Lenticular Opacities

  • 1991: At the NIH Consensus Conference of Acoustic Neuroma, the recommended was a change the terminology. Since Cranial Nerve 8 Schwann Cells form on the Vestibular rather than Acoustic branch, the term should be called Vestibular Schwannoma. [1]

  • 1992: Two types of NF2 inaccurately identified as two simple types:[3]
    1. Gardner Type: mild with late onset and few tumors other than Vestibular Schwannoma
    2. Wishart Type: severe, early onset with multiple tumors

  • 1992: The development of the 8 Electrode ABI, allowed for a wider range of sounds, this new implant was completely different from the first and was implanted in 25 individuals.

  • 1993: Development of Magnetic Resonance Venography (MRV). MRI equipment used to see veins and arteries in the brain.

  • 1996: It was determined numbers of individuals with NF2 were higher than previously believed due to Genetic Mosaicism. Individuals with Mosaic NF2 might only have, Unilateral Vestibular Schwannoma (VS on one side), or possibly no tumors, but can have children with all tumor types and issues.
  • Genetic Mosaicism is when cells in an individual have a different genetic makeup. In Mosaic NF2 that means not every cell in an individual's body has NF2. Individuals with Mosaic NF2 cannot always be confirmed with a genetic test. The possibility of Mosaicism is one of the reasons genetic testing is not always used to determine if an individual has NF2, but instead MRIs and other tests instead.

  • 1996: Schwannomatosis was described as a separate clinical condition from other forms of NF: Tumors similar to NF2, except bilateral hearing loss is not an issue. Often as many body tumors as NF1, except where NF1 body tumors are Neurofibromas, for people with Schwannomatosis the tumors are Schwannomas which result in chronic pain. [3]

  • 1997: Diagnostic Method of the Manchester Criteria included important revisions of classifies of NF2 as any one of the following:[3]
    • Bilateral Vestibular Schwannoma
    • 1 or more 1st degree relative with NF2 + unilateral Vestibular Schwannoma at <30 years;
    • 2 of the following: Meningioma, Glioma, Schwannoma, Juvenile Posterior Lenticular Opacities.

  • 1999: The latest in developments of ABIs. ABIs with 21 Electrodes for sound. Since this the only developments for ABIs is upgradable external parts for additional changes in sound quality and ease of use.

  • 2000: Pre-symptomatic diagnosis with genetic test can be helpful for ~66% of all classically affected NF2 patients.

  • 2003: Schwannomatosis is molecularly and clinically distinct from NF2.[3]

  • 2003: Development of high resolution NF2-specific diagnostic microarray for the detection of condition causing gene deletions.[3]
    • NF1: Chromosome 17q11.2
    • NF2: Chromosome 22q12.2

  • 2005: Clear distinctive characteristics between NF2 and Schwannomatosis finally classified, like NF2 also on Chromosome 22q12 but with a distinction in characteristics but with an alteration to the SMARCB1 protein, where NF2 is a result of the Merlin protein.[3]

  • 2005: Development of Polymerase Chain Reaction Method (PCR Method) to detect deletions and duplications of the NF2 gene.

  • 2007: Chromogenic in situ hybridization (CISH) validated as a reliable method for assessing NF2 gene deletions in sporadic Schwannomas, Meningiomas and Ependymomas.

  • 2007: Endoscopic Endonasal Surgery allows for tumor removal through the nose for previously inoperable tumors.

  • 2009: Development of method of Volumetric Measurements of tumors seen with MRIs.

  • 2010: Transorbital Neuroendoscopic Surgery allows for tumor removal through the eye for previously inoperable tumors.

  • 2011: Baser Criteria was created to help with earlier diagnosis for individuals with potential Spontaneous NF2 Mutation, to require genetic testing if an individual shows any physical signs of NF2. The Baser Criteria is named after Dr. Michael E Baser.

  • 2013: 3D Camera Surgery Assistance. The use of an Laparoscopic surgery type Endoscope in nasal cavity to see and remove tumor mass.

  • 2013: Organs Made Transparent with New Imaging Technique: Mouse Stage. Method CLARITY (Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging / Immunostaining / In situ hybridization-compatible Tissue-hYdrogel)[3]

  • 2013: Individuals showing signs of Schwannomatosis with no markers for the SMARCB1 protein were finally established to have an alteration of the LZTR1 protein.[5]

  • 2014: Genetic testing for accurate Schwannomatosis diagnosis was finally available. Some diagnosed as NF1 or NF2 were finally able to be properly diagnosed with Schwannomatosis.

  • 2016: Updated diagnosis of NF2: Baser Criteria - There are variations on what issues NF2 may result in and determination of diagnosis and the Baser Criteria says an individual has NF2 if one of the following applies:
    Primary Finding Added Features needed for Diagnosis
    Bilateral Vestibular Schwannoma
    None
    First degree relative with NF2


    Unilateral Vestibular Schwannoma, or
    Any 2 other NF2-associated lessons:
    Meningioma, Schwannoma, Glioma, Cataracts
    Unilateral Vestibular Schwannoma


    Any 2 other NF2-associated lesions:
    Meningioma, Schwannoma, Glioma, Neurofibroma, Cataract
    Multiple Meningiomas


    Unilateral Vestibules Schwannoma, or
    Any 2 other NF2 Associated lesions:
    Schwannoma, Glioma, Neurofibroma, Cataracts

2. Reference Sources

  1. Evans, D. G., et al. "A genetic study of type 2 neurofibromatosis in the United Kingdom. I. Prevalence, mutation rate, fitness, and confirmation of maternal transmission effect on severity." Journal of medical genetics 29.12 (1992): 841-846. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1016198/
  2. Gerber, P. A., Antal, A. S., Neumann, N. J., Homey, B., Matuschek, C., Peiper, M., ... & Bolke, E. (2009). Neurofibromatosis. European journal of medical research, 14(3), 102. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3352057
  3. Congressionally Directed Medical Research Programs. NF2 Storyboard. (2010) http://cdmrp.army.mil/nfrp/pdf/NF2storyboard.pdf
  4. Chung, Kwanghun, et al. "Structural and molecular interrogation of intact biological systems." Nature 497.7449 (2013): 332-337. http://www.nature.com/nature/journal/v497/n7449/abs/nature12107.html
  5. Piotrowski, A., Xie, J., Liu, Y. F., Poplawski, A. B., Gomes, A. R., Madanecki, P., ... & Messiaen, L. M. (2013). Germline loss-of-function mutations in LZTR1 predispose to an inherited disorder of multiple schwannomas. Nature genetics. http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.2855.html
  6. Baser, M. E., Friedman, J. M., Joe, H., Shenton, A., Wallace, A. J., Ramsden, R. T., & Evans, D. G. R. (2011). Empirical development of improved diagnostic criteria for neurofibromatosis 2. Genetics in Medicine, 13(6), 576-581. http://www.nature.com/gim/journal/v13/n6/abs/gim9201192a.html
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