Updated diagnostic criteria and nomenclature for neurofibromatosis type 2 and schwannomatosis: An international consensus recommendation.

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. 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. 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. 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.

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Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of Interest 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.