An international committee of NF experts utilized a multi-step process conducted over the past several years to acquire clinical insight for the revised criteria that included the Delphi method, which utilized electronic questionnaires to gather information, as well as face-to-face meetings.
Revised Diagnostic Criteria
Based on this process, the international committee reached a consensus that new diagnostic criteria were needed for NF1, NF2, and schwannomatosis. The updated diagnostic criteria for NF2 and schwannomatosis were published in 2022 in Genetics in Medicine, the official journal of the American College of Medical Genetics and Genomics (ACMG); a separate publication with an update to the diagnostic criteria for NF1 was published in 2021, also in Genetics in Medicine, and was the subject of a previous blog (A Discussion of Revised Diagnostic Criteria Released for NF1 and Legius Syndrome - Neurofibromatosis Program | UAB).
In addition to changes in NF diagnostic criteria, the committee recommended the term “schwannomatosis” be used as an umbrella term for conditions that predispose to schwannomas, which includes what has been known an NF2 and schwannomatosis, while further classifying each type of schwannomatosis by the gene containing the disease-causing pathogenic variant.
This change was based on the concern that the nomenclature for NF2 and schwannomatosis was misleading because neither of these disorders includes neurofibromas as a major clinical feature, as NF1 does, but instead involves schwannomas as the primary tumor type. In the past, the distinction among different types of NF was not appreciated, namely that the pathology of different nerve sheath tumors is distinctive, including the genetics and the context in which they occur.
Updated Terms for NF2 and Schwannomatosis
The committee recommended that the name of NF1 remain unchanged and that NF2 and the other cluster of NF-related conditions be renamed under schwannomatosis, as follows:
- NF2-related schwannomatosis (formerly called NF2)
- SMACRB1-related schwannomatosis
- LZTR1-related schwannomatosis
- 22q-related schwannomatosis
- Schwannomatosis NOS (not otherwise specified) for patients who have not had genetic testing
- Schwannomatosis NEC (not elsewhere classified) for patients in whom genetic testing of blood/saliva and tumors failed to detect a pathogenic variant.
These updated naming conventions define the conditions according to the underlying molecular mechanisms and align with the current approach used in genetics of naming a condition based on the phenotype and major clinical features or the gene associated with that specific phenotype. An advantage of this format is that it allows for adding other types of schwannomatosis when and if new genes are identified.