Abstract
Four unrelated patients having an unusual clinical phenotype, including multiple peripheral nerve sheath tumors, are reported. Their clinical features were not typical of any known familial tumor syndrome. The patients had multiple painful neurofibromas, including bilateral orbital plexiform neurofibromas, and spinal as well as mucosal neurofibromas. In addition, they exhibited a marfanoid habitus, shared similar facial features, and had enlarged corneal nerves as well as neuronal migration defects. Comprehensive NF1, NF2 and SMARCB1 mutation analyses revealed no mutation in blood lymphocytes and in schwann cells cultured from plexiform neurofibromas. Furthermore, no mutations in RET, PRKAR1A, PTEN and other RAS-pathway genes were found in blood leukocytes. Collectively, the clinical and pathological findings in these four cases fit no known syndrome and likely represent a new disorder.
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Acknowledgements
This work was supported by the Fonds voor Wetenschappelijk Onderzoek (FWO)-Vlaanderen (G.0578.06) (EL), a Concerted Action Grant (GOA/11/010) from the KULeuven, the FWO scientific research community (W0.027.09) (EL) and the Interuniversity Attraction Poles (IAP) granted by the Federal Office for Scientific, Technical and Cultural Affairs, Belgium (2007–2011; P5/25) (EL). HB was supported by the Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-Vlaanderen). Additional support was provided by NF Inc., MN, USA (NFIM#2) (DBV). We thank Kara A Mensink, MS, CGC, for helpful edits and Cheryl Dowse for technical assistance.
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Babovic-Vuksanovic, D., Messiaen, L., Nagel, C. et al. Multiple orbital neurofibromas, painful peripheral nerve tumors, distinctive face and marfanoid habitus: a new syndrome. Eur J Hum Genet 20, 618–625 (2012). https://doi.org/10.1038/ejhg.2011.275
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DOI: https://doi.org/10.1038/ejhg.2011.275
