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Children's Tumour Foundation of Australia

Diagnostic Criteria Update

NF2 and Schwannomatosis Diagnostic Criteria, 2022 Update

The information on this page has been provided by the CTF in the USA, which can be found here.

An update to the diagnostic criteria for the genetic conditions formerly referred to as neurofibromatosis type two (NF2) and schwannomatosis has been published in Genetics in Medicine, the official journal of the American College of Medical Genetics and Genomics (ACMG). 

Among other important changes, the term "schwannomatosis" was proposed in this publication as an umbrella term for NF2 and schwannomatosis, further classifying each type of schwannomatosis by the gene containing the disease-causing pathogenic variant (formerly called a gene mutation). A separate publication with an update to the diagnostic criteria for NF1 was published last year and can be accessed below. 

CLICK HERE to read the open-access version of this important article.


The former diagnostic criteria for NF2 and schwannomatosis classified patients primarily based on clinical features; however, it is now apparent that the manifestations of these diseases span the same continuum. For this reason, "schwannomatosis" no longer defines a distinct syndrome, but is now used as an umbrella term to describe the overlapping conditions in which a patient has many schwannomas. Retiring "NF2" will also minimize misdiagnosis with neurofibromatosis type 1.

The updated diagnostic criteria for schwannomatosis classify each disorder according to the specific gene harboring a pathogenic variant (formerly called a gene mutation). Therefore, NF2 is now termed NF2-related schwannomatosis. What was previously referred to as “schwannomatosis” is now termed either SMARCB1-related schwannomatosis, LZTR1-related schwannomatosis, 22q-related schwannomatosis, schwannomatosis-NOS (not otherwise specified), or schwannomatosis NEC (not elsewhere classified). 

There has been some confusion and overlap in the diagnosis of all types of neurofibromatosis and schwannomatosis, and the updated criteria intend to improve patient care by reducing misdiagnosis:

  • 9% of patients with a clinical diagnosis of schwannomatosis actually had NF2 upon genetic analysis
  • 1-2% of patients with a clinical diagnosis of NF2 actually had schwannomatosis upon genetic analysis
  • Significant overlap in features of schwannomatosis with mosaic NF2 patients
  • No mention of the LZTR1 gene or other genetic features in previous criteria
  • A new awareness of the hybrid nerve sheath tumor (a close relative of schwannoma and neurofibroma) for use in the diagnosis of schwannomatosis

NF1 Diagnostic Criteria 2021 Update

An update to the Diagnostic Criteria for neurofibromatosis type one (NF1) was published in Genetics in Medicine, the official journal of the American College of Medical Genetics and Genomics (ACMG) in May of 2021. 


Historically, there has been some confusion between an NF1 and NF2 diagnosis, and the updated criteria intends to clarify that, and other areas of confusion, for practitioners and the general community. It is important to note that the past diagnostic criteria were established prior to:

  • Discovery of the genes that cause NF1, NF2, and schwannomatosis
  • Ability to perform genetic testing
  • Recognition of schwannomatosis as distinct from NF2
  • New clinical information about NF1, NF2, and schwannomatosis

NF1 Criteria Infographic

About the Diagnostic Criteria Update


The diagnostic criteria for NF1 and NF2 were previously established at the National Institutes of Health (NIH) consensus meeting in 1987, and the diagnostic criteria for schwannomatosis was established in 2005. Since that time, and thanks to the arduous work of so many CTF-funded researchers, there has been a tremendous increase in knowledge about these genetic disorders. 

In 2017, a group of NF investigators reached out to CTF USA to sponsor a revision of the NF diagnostic criteria, sparking a multi-year process. The Children’s Tumor Foundation USA hosted a two-day workshop in June of 2018, that included 32 international experts who reviewed and proposed revisions to the diagnostic criteria of the neurofibromatoses. 

We expect that these diagnostic criteria will continue to be revised as investigators evaluate new data and recommend proposed changes based on input from the community. The resulting changes will have a far-reaching impact, and will greatly improve the accuracy of diagnosis and care for patients living with all forms of NF.

15 May 2023
Category: Blog