Historical Development of Diagnostic Criteria for NF2-related Schwannomatosis

Abstract

NF2-related schwannomatosis (NF2; previously termed neurofibromatosis type 2) is a tumor-prone disorder characterized by development of multiple schwannomas and meningiomas. The diagnostic criteria of NF2 have been regularly revised. Clinical criteria for NF2 were first formulated at the National Institutes of Health Consensus Conference in 1987 and revised in 1990. Revised criteria were also proposed by the Manchester group in 1992 and by the National Neurofibromatosis Foundation (NNFF) in 1997. The 2011 Baser criteria improved the sensitivity of diagnostic criteria, particularly for patients without bilateral vestibular schwannomas. Revisions to the Manchester criteria were published in 2019, with replacement of "glioma" by "ependymoma," removal of "neurofibroma," addition of an age limit of 70 years for development of vestibular schwannomas, and introduction of molecular criteria, which led to the most widely used criteria. In 2022, the criteria were reviewed and updated by the international committee of NF experts. In addition to changes in diagnostic criteria, the committee recommended the use of "schwannomatosis" as an umbrella term for conditions that predispose to schwannomas. Each type of schwannomatosis was classified by the gene containing the disease-causing pathogenic variant. Molecular data from NF2 patients led to further clarification of the diagnostic criteria for NF2 mosaic phenotypes. Given all these changes, the diagnostic criteria of NF2 may be confusing. Herein, to help healthcare professionals who diagnose NF2 conditions in the clinical setting, we review the historical development of diagnostic criteria.