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

Scott R Plotkin ¹, Ludwine Messiaen ², Eric Legius ³, Patrice Pancza ⁴, Robert A Avery ⁵, Jaishri O Blakeley ⁶, Dusica Babovic-Vuksanovic ⁷, Rosalie Ferner ⁸, Michael J Fisher ⁹, Jan M Friedman ¹⁰, Marco Giovannini ¹¹, David H Gutmann ¹², Clemens Oliver Hanemann ¹³, Michel Kalamarides ¹⁴, Hildegard Kehrer-Sawatzki ¹⁵, Bruce R Korf ², Victor-Felix Mautner ¹⁶, Mia MacCollin ¹⁷, Laura Papi ¹⁸, Katherine A Rauen ¹⁹, Vincent Riccardi ²⁰, Elizabeth Schorry ²¹, Miriam J Smith ²², Anat Stemmer-Rachamimov ²³, David A Stevenson ²⁴, Nicole J Ullrich ²⁵, David Viskochil ²⁶, Katharina Wimmer ²⁷, Kaleb Yohay ²⁸; International Consensus Group on Neurofibromatosis Diagnostic Criteria (I-NF-DC); Susan M Huson ²⁹, Pierre Wolkenstein ³⁰, D Gareth Evans ²²

Collaborators, Affiliations expand

• PMID: 35674741
• DOI: 10.1016/j.gim.2022.05.007

Free article

Abstract

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.

Keywords: NF2; Neurofibromatosis; SMARCB1; Schwannomatosis; lztr1.