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Review | Open Access
Rare Disease and Orphan
Drugs Journal
Lightner. Rare Dis Orphan Drugs J. 2026;5:1 DOI:10.20517/rdodj.2025.11
Neurofibromatosis type 2-related schwannomatosis:
an update
Donita Lightner
Keywords: Abstract
Neurofibromatosis type 2,
NF2-related Neurofibromatosis type 2-related schwannomatosis was first described in 1822. Although
schwannomatosis, it is a different entity with a distinct presentation, it was initially confused with
schwannomatosis, neurofibromatosis type 1 by our forefathers and continues to be confused by clinicians and
vestibular schwannoma, patients today. Historically, physicians recognized that some patients presented earlier and
meningioma
had more severe phenotypes (Wishart versus Gardner). This has been better understood
Citation: Lightner D. through genetic and molecular studies, which indicate that the differences are likely related
Neurofibromatosis type 2- to mosaicism rather than germline mutations. Recently, the nomenclature was changed to
related schwannomatosis: Neurofibromatosis type 2-related schwannomatosis, which is more appropriate. Diagnostic
an update. Rare Dis Orphan
Drugs J. 2026;5:1. https://dx criteria have also been modified with the addition of genetic testing results. Treatment
.doi.org/10.20517/rdodj.202 remains a conundrum. Historically, surgery has been the mainstay; however, it is risky for
5.11 large tumors. Vascular endothelial growth factor inhibitors, such as bevacizumab, have
been helpful in reducing the size of acoustic schwannomas and have been shown to
Received: 12 Feb 2025
First Decision: 4 Jul 2025 preserve hearing, along with alleviating other symptoms. However, the medication has
Revised: 18 Aug 2025 clear toxicities, and patients frequently become dependent on treatment or even develop
Accepted: 19 Sep 2025 tumor resistance. Numerous trials are ongoing to investigate reduced dosing regimens of
Published: 7 Jan 2026 vascular endothelial growth factor inhibitors and alternative molecular targets to determine
whether the natural progression of the disease can be altered. Gene therapy is on the
Academic Editor:
Daniel Scherman horizon.
Copy Editor:
Ping Zhang
Production Editor:
Ping Zhang INTRODUCTION
History
Depictions of neurofibromatosis involving skin lesions were found even among
ancient Egyptian findings dating back to 1500 BCE. That being said, most of these
descriptions involve individuals with neurofibromatosis type 1 (NF1). It was not
until 1777 that Eduard Sandifort, a professor of anatomy at the University of Leiden
in the Netherlands, first described an acoustic neuroma at autopsy. Later, John H.
Wishart, a Scottish surgeon and president of the Royal College of Surgeons in
Edinburgh, described the clinical course and subsequent autopsy findings of Michael
Blair. This individual succumbed at 21 years of age after developing progressive
hearing loss, intractable headaches, and seizures. When Dr. Wishart performed the
Departments of Neurology & Pediatrics, University of Kentucky, Lexington, KY 40536, USA.
Correspondence to: Dr. Donita Lightner, Departments of Neurology & Pediatrics, University of Kentucky, Lexington, KY 40536, USA. E-
mail: donita.lightner@uky.edu
www.oaepublish.com Submit a Manuscript: https://ucenter.oaepublish.com
