TY - JOUR
T1 - Updated diagnostic criteria and nomenclature for neurofibromatosis type 2 and schwannomatosis
T2 - An international consensus recommendation
AU - International Consensus Group on Neurofibromatosis Diagnostic Criteria (I-NF-DC)
AU - Plotkin, Scott R.
AU - Messiaen, Ludwine
AU - Legius, Eric
AU - Pancza, Patrice
AU - Avery, Robert A.
AU - Blakeley, Jaishri O.
AU - Babovic-Vuksanovic, Dusica
AU - Ferner, Rosalie
AU - Fisher, Michael J.
AU - Friedman, Jan M.
AU - Giovannini, Marco
AU - Gutmann, David H.
AU - Hanemann, Clemens Oliver
AU - Kalamarides, Michel
AU - Kehrer-Sawatzki, Hildegard
AU - Korf, Bruce R.
AU - Mautner, Victor Felix
AU - MacCollin, Mia
AU - Papi, Laura
AU - Rauen, Katherine A.
AU - Riccardi, Vincent
AU - Schorry, Elizabeth
AU - Smith, Miriam J.
AU - Stemmer-Rachamimov, Anat
AU - Stevenson, David A.
AU - Ullrich, Nicole J.
AU - Viskochil, David
AU - Wimmer, Katharina
AU - Yohay, Kaleb
AU - Anten, Monique
AU - Aylsworth, Arthur
AU - Baralle, Diana
AU - Barbarot, Sebastien
AU - Barker, Fred
AU - Ben-Shachar, Shay
AU - Bergner, Amanda
AU - Bessis, Didier
AU - Blanco, Ignacio
AU - Cassiman, Catherine
AU - Ciavarelli, Patricia
AU - Clementi, Maurizio
AU - Frébourg, Thierry
AU - Gomes, Alicia
AU - Halliday, Dorothy
AU - Helen Hanson Arvid Heiberg, Chris Hammond
AU - Joly, Pascal
AU - Jordan, Justin T.
AU - Karajannis, Matthias
AU - Kroshinsky, Daniela
AU - Le, Lu
N1 - Funding Information:
R.A.A., C.O.H., and K.A.R declare no conflicts of interest. D.B.-V. is a scientific advisor for AstraZeneca, L.P. and receives grant support from the Department of Defense and SpringWorks Therapeutics. J.B. is a member of the Children’s Tumor Foundation Medical Advisory Committee and the Clinical Care Advisory Board. D.G.E. is a member of the Children’s Tumor Foundation Clinical Care Advisory Board-Europe and has received consultancy fees from AstraZeneca, SpringWorks Therapeutics, and Recursion. R.F. is a member of the Children’s Tumor Foundation Clinical Care Advisory Board-Europe and is a medical advisor for AstraZeneca. M.J.F. is a member of the Children’s Tumor Foundation Medical Advisory Committee. J.M.F. is a member of the Children’s Tumor Foundation Clinical Care Advisory Board. M.G. receives grant support from NF2 Therapeutics, Inc and is a consultant for Puma Biotechnology. D.H.G. declares no conflicts of interest. M.K. is a paid consultant for Regeneron Pharmaceuticals. S.M.H. declares no conflicts of interest. H.K.-S. declares no conflicts of interest. B.R.K is a member of the Children’s Tumor Foundation Medical Advisory Committee (Chair) and is on the medical advisory boards of Genome Medicine and iNfixion Bioscience. E.L. is a member of the Children’s Tumor Foundation Clinical Care Advisory Board-Europe. V.-F.M. is a member of the Children’s Tumor Foundation Clinical Care Advisory Board-Europe. M.M. declares no conflicts of interest. L.P. declares no conflicts of interest. L.M. directed the Medical Genomics Laboratory at University of Alabama, Birmingham, which specializes in genetic testing for all forms of the neurofibromatosis, until April 2021. P.P. is employed by the Children’s Tumor Foundation. S.R.P is a member of the Children’s Tumor Foundation Clinical Care Advisory Board (Chair, United States) and Europe; is cofounder of NFlection Therapeutics, Inc and NF2 Therapeutics, Inc; and is a consultant for Akouos, AstraZeneca, and SonALASense. V.R. declares no conflicts of interest. E.S. is a member of the Children’s Tumor Foundation Clinical Care Advisory Board and receives Department of Defense funding as a site for NF Clinical Trials Consortium. M.J.S declares no conflicts of interest. A.S.-R. declares no conflicts of interest. D.A.S. is a consultant for Alexion Pharmaceuticals, Inc. N.J.U is a member of the Children’s Tumor Foundation Clinical Care Advisory Board, serves on the board of Neurofibromatosis Northeast, and received a consultant fee from Astra Zeneca. D.V. is a member of the Children’s Tumor Foundation Medical Advisory Committee and Clinical Care Advisory Board, is a member of the AstraZeneca speaker’s bureau, and is on the Sanofi-Genzyme—MPS Board of Advisors. K.W. declares no conflicts of interest. P.W. is a member of the Children’s Tumor Foundation Clinical Care Advisory Board-Europe (Chair). K.Y. is a member of the Children’s Tumor Foundation Clinical Care Advisory Board, received a consultant fee from AstraZeneca, is on the Scientific Advisory Board for iNFixion Bioscience, is member of the Programmatic Review Committee for the Department of Defense, Congressionally Directed Medical Research Program, and Neurofibromatosis Research Program.
Funding Information:
The authors would like to thank the Children’s Tumor Foundation and Annette Bakker for supporting the revision process both financially and administratively. The authors would also like to thank the patients and foundations, particularly the members of the NF Collective for their attendance at informational webinars and for providing critical input. D.G.E. is supported by the NIHR Manchester Biomedical Research Centre (IS-BRC-1215-20007). S.R.P. is supported by NIH 5R01CA201130-04.
Publisher Copyright:
© 2022 The Authors
PY - 2022/9
Y1 - 2022/9
N2 - Purpose: Neurofibromatosis type 2 (NF2) and schwannomatosis (SWN) are genetically distinct tumor predisposition syndromes with overlapping phenotypes. We sought to update the diagnostic criteria for NF2 and SWN by incorporating recent advances in genetics, ophthalmology, neuropathology, and neuroimaging. Methods: We used a multistep process, beginning with a Delphi method involving global disease experts and subsequently involving non-neurofibromatosis clinical experts, patients, and foundations/patient advocacy groups. Results: We reached consensus on the minimal clinical and genetic criteria for diagnosing NF2 and SWN. These criteria incorporate mosaic forms of these conditions. In addition, we recommend updated nomenclature for these disorders to emphasize their phenotypic overlap and to minimize misdiagnosis with neurofibromatosis type 1. Conclusion: The updated criteria for NF2 and SWN incorporate clinical features and genetic testing, with a focus on using molecular data to differentiate the 2 conditions. It is likely that continued refinement of these new criteria will be necessary as investigators study the diagnostic properties of the revised criteria and identify new genes associated with SWN. In the revised nomenclature, the term “neurofibromatosis 2” has been retired to improve diagnostic specificity.
AB - Purpose: Neurofibromatosis type 2 (NF2) and schwannomatosis (SWN) are genetically distinct tumor predisposition syndromes with overlapping phenotypes. We sought to update the diagnostic criteria for NF2 and SWN by incorporating recent advances in genetics, ophthalmology, neuropathology, and neuroimaging. Methods: We used a multistep process, beginning with a Delphi method involving global disease experts and subsequently involving non-neurofibromatosis clinical experts, patients, and foundations/patient advocacy groups. Results: We reached consensus on the minimal clinical and genetic criteria for diagnosing NF2 and SWN. These criteria incorporate mosaic forms of these conditions. In addition, we recommend updated nomenclature for these disorders to emphasize their phenotypic overlap and to minimize misdiagnosis with neurofibromatosis type 1. Conclusion: The updated criteria for NF2 and SWN incorporate clinical features and genetic testing, with a focus on using molecular data to differentiate the 2 conditions. It is likely that continued refinement of these new criteria will be necessary as investigators study the diagnostic properties of the revised criteria and identify new genes associated with SWN. In the revised nomenclature, the term “neurofibromatosis 2” has been retired to improve diagnostic specificity.
KW - NF2
KW - Neurofibromatosis
KW - SMARCB1
KW - Schwannomatosis
KW - lztr1
UR - http://www.scopus.com/inward/record.url?scp=85132738125&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85132738125&partnerID=8YFLogxK
U2 - 10.1016/j.gim.2022.05.007
DO - 10.1016/j.gim.2022.05.007
M3 - Article
C2 - 35674741
AN - SCOPUS:85132738125
SN - 1098-3600
VL - 24
SP - 1967
EP - 1977
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 9
ER -