Article

Genetics in Medicine (2011) 13, 576–581; doi:10.1097/GIM.0b013e318211faa9

Empirical development of improved diagnostic criteria for neurofibromatosis 2

Michael E Baser1,, Jan M Friedman2, Harry Joe3, Andrew Shenton4,, Andrew J Wallace4, Richard T Ramsden5 and D Gareth R Evans4

  1. 1Los Angeles, California, University of British Columbia and the Child & Family Research Institute, Vancouver, British Columbia Canada
  2. 2Department of Medical Genetics, University of British Columbia and the Child & Family Research Institute, Vancouver, British Columbia Canada
  3. 3Department of Statistics, University of British Columbia, Vancouver, British Columbia Canada
  4. 4Academic Department of Medical Genetics, St. Mary's Hospital, Manchester, United Kingdom
  5. 5Department of Otolaryngology, Manchester Royal Infirmary, Manchester, United Kingdom

Correspondence: Jan M. Friedman, MD, PhD, Medical Genetics Research Unit, Box 153, Children's and Women's Hospital, 4500 Oak Street, Vancouver, British Columbia V6H 3N1, Canada. E-mail: frid@interchange.ubc.ca.

Deceased.

Received 23 August 2010; Accepted 14 January 2011; Published online 29 March 2011.

Disclosure: The authors declare no conflict of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.geneticsinmedicine.org).

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Abstract

Purpose: Four sets of clinical diagnostic criteria have been proposed for neurofibromatosis 2, but all have low sensitivity at the time of initial clinical assessment for the disease among patients with a negative family history who do not present with bilateral vestibular schwannomas. We have empirically developed and tested an improved set of diagnostic criteria that uses current understanding of the natural history and genetic characteristics of neurofibromatosis 2 to increase sensitivity while maintaining very high specificity.

Methods: We used data from the UK Neurofibromatosis 2 Registry and Kaplan-Meier curves to estimate frequencies of clinical features at various ages among patients with or without unequivocal neurofibromatosis 2. On the basis of this analysis, we developed the Baser criteria, a new diagnostic system that incorporates genetic testing and gives more weight to the most characteristic features and to those that occur before 30 years of age.

Results: In an independent validation subset of patients with unequivocal neurofibromatosis 2, the Baser criteria increased diagnostic sensitivity to 79% (9–15% greater than previous sets of criteria) while maintaining 100% specificity at the age at onset of the first characteristic sign of neurofibromatosis 2.

Conclusion: The Baser criteria permit early diagnosis in a greater proportion of patients with neurofibromatosis 2 than previous sets of diagnostic criteria.

Keywords:

neurofibromatosis 2; NF2; diagnosis; diagnostic criteria; genetic testing