The Children’s Tumor Foundation (CTF) today announced the landmark publication of updated diagnostic criteria for the genetic disorder neurofibromatosis type 2 (NF2) and schwannomatosis in Genetics in Medicine, the official journal of the American College of Medical Genetics and Genomics. The new publication is the result of an extensive, multi-year collaborative effort of leading neurofibromatosis experts from around the globe, and is aimed at improving the accuracy of diagnosis of NF2 and schwannomatosis in patients, thus ultimately leading to improved care and quality of life for those patients.
Significantly, 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). 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.
The updated diagnostic criteria for schwannomatosis classify each disorder according to the specific gene harboring a pathogenic variant. 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
The original diagnostic criteria for NF1 and NF2 were 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, there has been an explosion of knowledge about these genetic disorders, including the discovery of the genes that cause NF1, NF2, and schwannomatosis, as well as the technological development of genetic testing. In recent years, NF clinicians have noted that an updated consensus was needed to better communicate (for both medical professionals and patients) the distinctions between NF1, NF2, and schwannomatosis, as patients were at times being misdiagnosed or receiving delayed diagnosis and care.
As a result, in 2017 a group of NF investigators reached out to the Children’s Tumor Foundation, the largest nongovernmental funder of all forms of NF research in the world, to sponsor a review and potential revision of the NF diagnostic criteria. That group of investigators grew into a worldwide effort that utilized the following guiding principles in the development of the updated criteria:
- Formulate a clear delineation between NF1, NF2, and schwannomatosis criteria
- Represent the best consensus among NF experts
- Reflect input from patients, caregivers, families, foundations, and advocacy groups
- Exclusively address the issues of diagnosis (rather than clinical management)
- Be broadly representative of medical specialties
- Be usable by general doctors as well as NF specialists
- Recognize advances in genetics without requiring genetic analysis for diagnosis
- Be relevant in different countries and health care systems, now and in coming years
Prior to today’s announcement of updated criteria for NF2 and schwannomatosis, the updated NF1, Legius syndrome, and mosaic NF criteria were previously announced last year.
In coming months, the Clinical Care Advisory Board of the Children’s Tumor Foundation, in partnership with NF clinics, medical groups, and other NF organizations, will roll out a multi-format education program of the updated criteria for both general physicians and NF experts, to increase knowledge and advance care of the various forms of neurofibromatosis and schwannomatosis.
Importantly, there will also be educational webinars in coming months for patients and caregivers to further explain the change in nomenclature. The overall aim of this work is to improve diagnosis and care, but also to ensure patients can accurately describe the particulars of the form of neurofibromatosis or schwannomatosis with which they live. Educational sessions to support this goal will be held throughout the coming year.
Additional information about today’s update, including a link to the publication in Genetics in Medicine, the researchers leading this effort, helpful explainer sheets and more (including the previously announced criteria for NF1) can all be found at: ctf.org/criteria.
