NF Criteria

Last Updated: 03/26/17

NF1, NF2 and Schwannomatosis

Topics Here

  1. Reason for Confusion
  2. NF2 Diagnosis Criteria
  3. NF1 Diagnosis Criteria
  4. Schwannomatosis Diagnosis Criteria
    • Confirmed (Definite) Diagnosis
    • Presumed (Probable) Diagnosis
  5. Reference Sources

Also See:

The three forms of Neurofibromatosis are; Neurofibromatosis Type 1 (NF1), Neurofibromatosis Type 2 (NF2) and Schwannomatosis (NF3, or SWN). The criteria for a diagnosis of each form of NF are included here and should be known by anyone with any form of NF.

It is important to understand that while NF is rare, it is statistically unlikely to have more than one form of NF. It is also statistically likely for a person with any of the three forms to be told they might have more than one form of NF. Since tumor growth for each is different it is important to know for a fact which form a person has. Due to similarities between the three forms, the accidental diagnosis of more than one form of NF is an easy one for doctors to make.

1. Reason for Confusion

All three forms of NF can result in tumors that can be seen from the skins surface, Cutaneous and Subcutaneous tumors. In a person with NF1 they are Neurofibroma. In people with NF2 or Schwannomatosis they would be Schwannoma. The distinction between the Neurofibroma and Schwannoma can only be determined in a biopsy and cannot be determined with use of an MRI. Some of these tumors are painful, some are not and there is typically a considerable amount more of these for people with NF1.

Skin discoloration spots of Café-au-lait Macules, is also primarily a NF1 concern, but people with NF2 and Schwannomatosis sometimes developing these, typically fewer than 6.

2. Criteria of Neurofibromatosis Type 2 Diagnosis - the Baser Criteria[2]

There have been different standards for diagnosis of NF2 since it was acknowledged as a condition different from NF1 and again when Schwannomatosis was classified as a separate condition.

NF2: Diagnostic Criteria

There have been different standards for diagnosis of NF2 since it was acknowledged as a condition different from NF1, again when Schwannomatosis was classified as a separate condition, and recently in 2016 as a result of a study in the UK.

As of 2016, the criteria for the diagnosis of NF2 is the Baser Criteria which is a revision of the Manchester Criteria. Michael E Baser, M.D. works with the team in Manchester UK, who have had a significant part in understandings of genetics and layout of criteria for the help of the diagnosis of the Neurofibromatosis conditions.

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

There are different doctor types that can be seen for a diagnosis of NF2.

Nf2: Genetic Criteria

In 2003 it was determined that NF2 was caused by damage to Chromosome 22q12.2 and can be found there in genetic testing.

3. Neurofibromatosis Type 1[3]

NF1: Diagnostic Criteria

The NIH diagnostic criteria for NF1 are met in an individual who has two or more of the following features:

  • Six or more Café-au-lait Macules Spots over 5mm in greatest diameter in pre-pubertal individuals and over 15mm in greatest diameter in post-pubertal individuals;
  • Two or more neurofibromas of any type or one plexiform neurofibroma;
  • Freckling in the Axillary or Inguinal regions;
  • Optic Glioma;
  • Two or more Lisch Nodules (Iris Hamartomas);
  • A distinctive osseous lesion such as sphenoid dysplasia or tibial pseudarthrosis;
  • A first-degree relative (parent, sibling, or offspring) with NF1 as defined by the above criteria;

Nf1: Genetic Criteria

In 2003 it was determined that NF1 was caused by damage to Chromosome 17q11.2 and can be found there in genetic testing.

4. Schwannomatosis[4]

A percentage of individuals with NF2 were displaying symptoms differently. In 2005 the development of genetics found out why when these individuals had a different genetic mutation. While some issues are in fact the same with individuals who have NF2, Schwannomatosis is in fact its own separate condition.

Schwannomatosis is caused by a mutation in the SMARCB1 gene (SWI/SNF) or the LZTR1 gene.

NF3: Diagnostic Criteria

The diagnostic criteria for a person to be diagnosed with Schwannomatosis follow a strict guideline established by the NIH. A diagnosis for Schwannomatosis may be established if a person meets one of the conditions identified below.

Confirmed (Definite) Diagnosis of Schwannomatosis:
  • 2 or more non-intradermal schwannomas (at least 1 with histological confirmation)
  • no evidence of a vestibular tumor on high-quality MRI scan no known constitutional NF2 mutation
  • 1 pathologically confirmed Non-Vestibular Schwannoma plus a first-degree relative who meets the above criteria
Presumed (Probable) Diagnosis of Schwannomatosis:
  • 2 or more non-intradermal schwannomas (at least 1 with histological confirmation)
  • no evidence of vestibular tumor on high quality MRI scan
  • no known constitutional NF2 mutation
  • no symptoms of 8th nerve dysfunction
  • radiographic evidence (image scans) of a Non-Vestibular Schwannoma plus a first degree relative meeting the criteria for definite Schwannomatosis

NF3: Genetic Criteria

In 2013, individuals showing signs of Schwannomatosis with no markers for the SMARCB1 protein were finally established to have an alteration of the LZTR1 protein.

Other Names

  1. multiple neurilemmomas
  2. multiple schwannomas
  3. neurilemmomatosis
  4. neurilemmomatosis, congenital cutaneous
  5. neurinomatosis
  6. neurofibromatosis type 3
5. Reference Sources
  1. NF1 and NF2: Hoa, M., & Slattery III, W. H. (2012). Neurofibromatosis 2. Otolaryngologic Clinics of North America, 45(2), 315. Available from: http://books.google.com/books?hl=en&lr=&id=kwdw7RQHeKcC&oi=fnd&pg=PA315&dq=nf2,+NIH,+Natural+History+Study&ots=1JzDOLvv__&sig=9mPRcLKT7aqMbU14304wCtlmaf8
  2. NF2: Bora, N., Miller, J. (2010). NF2 Storyboard. Available from: NIH Complete NF2 Timeline: 2010
  3. NF1: Friedman JM. Neurofibromatosis 1. 1998 Oct 2 [Updated 2012 May 3]. In: Pagon RA, Adam MP, Bird TD, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2013. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1109
  4. Schwannomatosis: Bacci, C., Sestini, R., Provenzano, A., Paganini, I., Mancini, I., Porfirio, B., ... & Papi, L. (2010). Schwannomatosis associated with multiple meningiomas due to a familial SMARCB1 mutation. Neurogenetics, 11(1), 73-80. Available from: http://link.springer.com/article/10.1007/s10048-009-0204-2#page-1
  5. Schwannomatosis: Piotrowski, A., Xie, J., Liu, Y. F., Poplawski, A. B., Gomes, A. R., Madanecki, P., ... & Messiaen, L. M. (2014). 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. Ruttledge, M. H., & Rouleau, G. A. (2005). Role of the neurofibromatosis type 2 gene in the development of tumors of the nervous system. Neurosurgical focus, 19(5), 1-5. http://thejns.org/doi/abs/10.3171/foc.2005.19.5.7
  7. Chen, H., Zhang, X., Zhang, Z., Yang, T., Wang, Z., & Wu, H. (2014). The role of NF2 gene mutations and pathogenesis-related proteins in sporadic vestibular schwannomas in young individuals. Molecular and cellular biochemistry, 1-8. http://link.springer.com/article/10.1007/s11010-014-2011-9
  8. 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/
  9. 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
  10. Congressionally Directed Medical Research Programs. NF2 Storyboard. (2010) http://cdmrp.army.mil/nfrp/pdf/NF2storyboard.pdf
  11. 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
  12. 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
  13. 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
  14. Ardern-Holmes, Simone, Gemma Fisher, and Kathryn North. "Neurofibromatosis Type 2: Presentation, Major Complications, and Management, With a Focus on the Pediatric Age Group." Journal of Child Neurology 32.1 (2017): 9-22. http://journals.sagepub.com/doi/abs/10.1177/0883073816666736
  15. National Institute of Health. Genetics Home Reference. "Schwannomatosis" (MArch 2017) https://ghr.nlm.nih.gov/condition/schwannomatosis#synonyms
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