Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation

Eric Legius; Ludwine Messiaen; Pierre Wolkenstein; Patrice Pancza; Robert A. Avery; Yemima Berman; Jaishri Blakeley; Dusica Babovic-Vuksanovic; Karin Soares Cunha; Rosalie Ferner; Michael J. Fisher; Jan M. Friedman; David H. Gutmann; Hildegard Kehrer-Sawatzki; Bruce R. Korf; Victor Felix Mautner; Sirkku Peltonen; Katherine A. Rauen; Vincent Riccardi; Elizabeth Schorry; Anat Stemmer-Rachamimov; David A. Stevenson; Gianluca Tadini; Nicole J. Ullrich; David Viskochil; Katharina Wimmer; Kaleb Yohay; Alicia Gomes; Justin T. Jordan; Victor Mautner; Vanessa L. Merker; Miriam J. Smith; Monique Anten; Arthur Aylsworth; Diana Baralle; Sebastien Barbarot; Fred Barker; Shay Ben-Shachar; Amanda Bergner; Didier Bessis; Ignacio Blanco; Catherine Cassiman; Patricia Ciavarelli; Maurizio Clementi; Thierry Frébourg; Marco Giovannini; Dorothy Halliday; Chris Hammond; C. O. Hanemann; Helen Hanson; International Consensus Group on Neurofibromatosis Diagnostic Criteria (I-NF-DC)

doi:10.1038/s41436-021-01170-5

Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation

Eric Legius^*, Ludwine Messiaen, Pierre Wolkenstein, Patrice Pancza, Robert A. Avery, Yemima Berman, Jaishri Blakeley, Dusica Babovic-Vuksanovic, Karin Soares Cunha, Rosalie Ferner, Michael J. Fisher, Jan M. Friedman, David H. Gutmann, Hildegard Kehrer-Sawatzki, Bruce R. Korf, Victor Felix Mautner, Sirkku Peltonen, Katherine A. Rauen, Vincent Riccardi, Elizabeth SchorryAnat Stemmer-Rachamimov, David A. Stevenson, Gianluca Tadini, Nicole J. Ullrich, David Viskochil, Katharina Wimmer, Kaleb Yohay, Alicia Gomes, Justin T. Jordan, Victor Mautner, Vanessa L. Merker, Miriam J. Smith, Monique Anten, Arthur Aylsworth, Diana Baralle, Sebastien Barbarot, Fred Barker, Shay Ben-Shachar, Amanda Bergner, Didier Bessis, Ignacio Blanco, Catherine Cassiman, Patricia Ciavarelli, Maurizio Clementi, Thierry Frébourg, Marco Giovannini, Dorothy Halliday, Chris Hammond, C. O. Hanemann, Helen Hanson, International Consensus Group on Neurofibromatosis Diagnostic Criteria (I-NF-DC)

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Purpose: By incorporating major developments in genetics, ophthalmology, dermatology, and neuroimaging, to revise the diagnostic criteria for neurofibromatosis type 1 (NF1) and to establish diagnostic criteria for Legius syndrome (LGSS). Methods: We used a multistep process, beginning with a Delphi method involving global experts and subsequently involving non-NF experts, patients, and foundations/patient advocacy groups. Results: We reached consensus on the minimal clinical and genetic criteria for diagnosing and differentiating NF1 and LGSS, which have phenotypic overlap in young patients with pigmentary findings. Criteria for the mosaic forms of these conditions are also recommended. Conclusion: The revised criteria for NF1 incorporate new clinical features and genetic testing, whereas the criteria for LGSS were created to differentiate the two conditions. It is likely that continued refinement of these new criteria will be necessary as investigators (1) study the diagnostic properties of the revised criteria, (2) reconsider criteria not included in this process, and (3) identify new clinical and other features of these conditions. For this reason, we propose an initiative to update periodically the diagnostic criteria for NF1 and LGSS. [Figure not available: see fulltext.].

Original language	English
Pages (from-to)	1506-1513
Number of pages	8
Journal	Genetics in Medicine
Volume	23
Issue number	8
DOIs	https://doi.org/10.1038/s41436-021-01170-5
Publication status	Published - 1 Aug 2021

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Cite this

Legius, E., Messiaen, L., Wolkenstein, P., Pancza, P., Avery, R. A., Berman, Y., Blakeley, J., Babovic-Vuksanovic, D., Cunha, K. S., Ferner, R., Fisher, M. J., Friedman, J. M., Gutmann, D. H., Kehrer-Sawatzki, H., Korf, B. R., Mautner, V. F., Peltonen, S., Rauen, K. A., Riccardi, V., ... International Consensus Group on Neurofibromatosis Diagnostic Criteria (I-NF-DC) (2021). Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation. Genetics in Medicine, 23(8), 1506-1513. https://doi.org/10.1038/s41436-021-01170-5

@article{d5e9fe4cf636446f9030b7ea92773866,

title = "Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation",

abstract = "Purpose: By incorporating major developments in genetics, ophthalmology, dermatology, and neuroimaging, to revise the diagnostic criteria for neurofibromatosis type 1 (NF1) and to establish diagnostic criteria for Legius syndrome (LGSS). Methods: We used a multistep process, beginning with a Delphi method involving global experts and subsequently involving non-NF experts, patients, and foundations/patient advocacy groups. Results: We reached consensus on the minimal clinical and genetic criteria for diagnosing and differentiating NF1 and LGSS, which have phenotypic overlap in young patients with pigmentary findings. Criteria for the mosaic forms of these conditions are also recommended. Conclusion: The revised criteria for NF1 incorporate new clinical features and genetic testing, whereas the criteria for LGSS were created to differentiate the two conditions. It is likely that continued refinement of these new criteria will be necessary as investigators (1) study the diagnostic properties of the revised criteria, (2) reconsider criteria not included in this process, and (3) identify new clinical and other features of these conditions. For this reason, we propose an initiative to update periodically the diagnostic criteria for NF1 and LGSS. [Figure not available: see fulltext.].",

author = "Eric Legius and Ludwine Messiaen and Pierre Wolkenstein and Patrice Pancza and Avery, {Robert A.} and Yemima Berman and Jaishri Blakeley and Dusica Babovic-Vuksanovic and Cunha, {Karin Soares} and Rosalie Ferner and Fisher, {Michael J.} and Friedman, {Jan M.} and Gutmann, {David H.} and Hildegard Kehrer-Sawatzki and Korf, {Bruce R.} and Mautner, {Victor Felix} and Sirkku Peltonen and Rauen, {Katherine A.} and Vincent Riccardi and Elizabeth Schorry and Anat Stemmer-Rachamimov and Stevenson, {David A.} and Gianluca Tadini and Ullrich, {Nicole J.} and David Viskochil and Katharina Wimmer and Kaleb Yohay and Alicia Gomes and Jordan, {Justin T.} and Victor Mautner and Merker, {Vanessa L.} and Smith, {Miriam J.} and Monique Anten and Arthur Aylsworth and Diana Baralle and Sebastien Barbarot and Fred Barker and Shay Ben-Shachar and Amanda Bergner and Didier Bessis and Ignacio Blanco and Catherine Cassiman and Patricia Ciavarelli and Maurizio Clementi and Thierry Fr{\'e}bourg and Marco Giovannini and Dorothy Halliday and Chris Hammond and Hanemann, {C. O.} and Helen Hanson and {International Consensus Group on Neurofibromatosis Diagnostic Criteria (I-NF-DC)}",

note = "Funding Information: The authors particularly thank the Children{\textquoteright}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 all Manchester NIHR Biomedical Research Centre (IS-BRC-1215-20007). Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = aug,

day = "1",

doi = "10.1038/s41436-021-01170-5",

language = "English",

volume = "23",

pages = "1506--1513",

journal = "Genetics in Medicine",

issn = "1098-3600",

publisher = "Nature Publishing Group",

number = "8",

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Legius, E, Messiaen, L, Wolkenstein, P, Pancza, P, Avery, RA, Berman, Y, Blakeley, J, Babovic-Vuksanovic, D, Cunha, KS, Ferner, R, Fisher, MJ, Friedman, JM, Gutmann, DH, Kehrer-Sawatzki, H, Korf, BR, Mautner, VF, Peltonen, S, Rauen, KA, Riccardi, V, Schorry, E, Stemmer-Rachamimov, A, Stevenson, DA, Tadini, G, Ullrich, NJ, Viskochil, D, Wimmer, K, Yohay, K, Gomes, A, Jordan, JT, Mautner, V, Merker, VL, Smith, MJ, Anten, M, Aylsworth, A, Baralle, D, Barbarot, S, Barker, F, Ben-Shachar, S, Bergner, A, Bessis, D, Blanco, I, Cassiman, C, Ciavarelli, P, Clementi, M, Frébourg, T, Giovannini, M, Halliday, D, Hammond, C, Hanemann, CO, Hanson, H & International Consensus Group on Neurofibromatosis Diagnostic Criteria (I-NF-DC) 2021, 'Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation', Genetics in Medicine, vol. 23, no. 8, pp. 1506-1513. https://doi.org/10.1038/s41436-021-01170-5

TY - JOUR

T1 - Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome

T2 - an international consensus recommendation

AU - Legius, Eric

AU - Messiaen, Ludwine

AU - Wolkenstein, Pierre

AU - Pancza, Patrice

AU - Avery, Robert A.

AU - Berman, Yemima

AU - Blakeley, Jaishri

AU - Babovic-Vuksanovic, Dusica

AU - Cunha, Karin Soares

AU - Ferner, Rosalie

AU - Fisher, Michael J.

AU - Friedman, Jan M.

AU - Gutmann, David H.

AU - Kehrer-Sawatzki, Hildegard

AU - Korf, Bruce R.

AU - Mautner, Victor Felix

AU - Peltonen, Sirkku

AU - Rauen, Katherine A.

AU - Riccardi, Vincent

AU - Schorry, Elizabeth

AU - Stemmer-Rachamimov, Anat

AU - Stevenson, David A.

AU - Tadini, Gianluca

AU - Ullrich, Nicole J.

AU - Viskochil, David

AU - Wimmer, Katharina

AU - Yohay, Kaleb

AU - Gomes, Alicia

AU - Jordan, Justin T.

AU - Mautner, Victor

AU - Merker, Vanessa L.

AU - Smith, Miriam J.

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 - Giovannini, Marco

AU - Halliday, Dorothy

AU - Hammond, Chris

AU - Hanemann, C. O.

AU - Hanson, Helen

AU - International Consensus Group on Neurofibromatosis Diagnostic Criteria (I-NF-DC)

N1 - Funding Information: The authors particularly 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 all Manchester NIHR Biomedical Research Centre (IS-BRC-1215-20007). Publisher Copyright: © 2021, The Author(s).

PY - 2021/8/1

Y1 - 2021/8/1

N2 - Purpose: By incorporating major developments in genetics, ophthalmology, dermatology, and neuroimaging, to revise the diagnostic criteria for neurofibromatosis type 1 (NF1) and to establish diagnostic criteria for Legius syndrome (LGSS). Methods: We used a multistep process, beginning with a Delphi method involving global experts and subsequently involving non-NF experts, patients, and foundations/patient advocacy groups. Results: We reached consensus on the minimal clinical and genetic criteria for diagnosing and differentiating NF1 and LGSS, which have phenotypic overlap in young patients with pigmentary findings. Criteria for the mosaic forms of these conditions are also recommended. Conclusion: The revised criteria for NF1 incorporate new clinical features and genetic testing, whereas the criteria for LGSS were created to differentiate the two conditions. It is likely that continued refinement of these new criteria will be necessary as investigators (1) study the diagnostic properties of the revised criteria, (2) reconsider criteria not included in this process, and (3) identify new clinical and other features of these conditions. For this reason, we propose an initiative to update periodically the diagnostic criteria for NF1 and LGSS. [Figure not available: see fulltext.].

AB - Purpose: By incorporating major developments in genetics, ophthalmology, dermatology, and neuroimaging, to revise the diagnostic criteria for neurofibromatosis type 1 (NF1) and to establish diagnostic criteria for Legius syndrome (LGSS). Methods: We used a multistep process, beginning with a Delphi method involving global experts and subsequently involving non-NF experts, patients, and foundations/patient advocacy groups. Results: We reached consensus on the minimal clinical and genetic criteria for diagnosing and differentiating NF1 and LGSS, which have phenotypic overlap in young patients with pigmentary findings. Criteria for the mosaic forms of these conditions are also recommended. Conclusion: The revised criteria for NF1 incorporate new clinical features and genetic testing, whereas the criteria for LGSS were created to differentiate the two conditions. It is likely that continued refinement of these new criteria will be necessary as investigators (1) study the diagnostic properties of the revised criteria, (2) reconsider criteria not included in this process, and (3) identify new clinical and other features of these conditions. For this reason, we propose an initiative to update periodically the diagnostic criteria for NF1 and LGSS. [Figure not available: see fulltext.].

U2 - 10.1038/s41436-021-01170-5

DO - 10.1038/s41436-021-01170-5

M3 - Article

SN - 1098-3600

VL - 23

SP - 1506

EP - 1513

JO - Genetics in Medicine

JF - Genetics in Medicine

IS - 8

ER -