S.R. Plotkin, D.G. Evans, and M. Giovannini were the meeting organizers and contributed equally to this work.
Article first published online: 7 FEB 2013
Copyright © 2013 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 161, Issue 3, pages 405–416, March 2013
How to Cite
Plotkin, S. R., Blakeley, J. O., Evans, D. G., Hanemann, C. O., Hulsebos, T. J.M., Hunter-Schaedle, K., Kalpana, G. V., Korf, B., Messiaen, L., Papi, L., Ratner, N., Sherman, L. S., Smith, M. J., Stemmer-Rachamimov, A. O., Vitte, J. and Giovannini, M. (2013), Update from the 2011 International Schwannomatosis Workshop: From genetics to diagnostic criteria. Am. J. Med. Genet., 161: 405–416. doi: 10.1002/ajmg.a.35760
How to Cite this Article: Plotkin SR, Blakeley JO, Evans DG, Hanemann CO, Hulsebos TJ, Hunter-Schaedle K, Kalpana GV, Korf B, Messiaen L, Papi L, Ratner N, Sherman LS, Smith MJ, Stemmer-Rachamimov AO, Vitte J, Giovannini M. 2013. Update from the 2011 International Schwannomatosis Workshop: From genetics to diagnostic criteria. Am J Med Genet Part A 161A: 405–416.
- Issue published online: 21 FEB 2013
- Article first published online: 7 FEB 2013
- Manuscript Accepted: 13 OCT 2012
- Manuscript Received: 24 JUL 2012
- rhabdoid tumor
Schwannomatosis is the third major form of neurofibromatosis and is characterized by the development of multiple schwannomas in the absence of bilateral vestibular schwannomas. The 2011 Schwannomatosis Update was organized by the Children's Tumor Foundation (www.ctf.org) and held in Los Angeles, CA, from June 5–8, 2011. This article summarizes the highlights presented at the Conference and represents the “state-of-the-field” in 2011. Genetic studies indicate that constitutional mutations in the SMARCB1 tumor suppressor gene occur in 40–50% of familial cases and in 8–10% of sporadic cases of schwannomatosis. Tumorigenesis is thought to occur through a four-hit, three-step model, beginning with a germline mutation in SMARCB1 (hit 1), followed by loss of a portion of chromosome 22 that contains the second SMARCB1 allele and one NF2 allele (hits 2 and 3), followed by mutation of the remaining wild-type NF2 allele (hit 4). Insights from research on HIV and pediatric rhabdoid tumors have shed light on potential molecular pathways that are dysregulated in schwannomatosis-related schwannomas. Mouse models of schwannomatosis have been developed and promise to further expand our understanding of tumorigenesis and the tumor microenvironment. Clinical reports have described the occurrence of intracranial meningiomas in schwannomatosis patients and in families with germline SMARCB1 mutations. The authors propose updated diagnostic criteria to incorporate new clinical and genetic findings since 2005. In the next 5 years, the authors expect that advances in basic research in the pathogenesis of schwannomatosis will lead toward clinical investigations of potential drug therapies. © 2013 Wiley Periodicals, Inc.