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Neurogenetics
Research paper
Schwannomatosis: a genetic and epidemiological study
  1. D Gareth Evans1,
  2. Naomi L Bowers1,
  3. Simon Tobi1,
  4. Claire Hartley1,
  5. Andrew J Wallace1,
  6. Andrew T King2,
  7. Simon K W Lloyd3,
  8. Scott A Rutherford2,
  9. Charlotte Hammerbeck-Ward2,
  10. Omar N Pathmanaban2,
  11. Simon R Freeman3,
  12. John Ealing4,
  13. Mark Kellett4,
  14. Roger Laitt2,
  15. Owen Thomas2,
  16. Dorothy Halliday5,
  17. Rosalie Ferner6,
  18. Amy Taylor7,
  19. Chris Duff8,
  20. Elaine F Harkness9,
  21. Miriam J Smith1
  1. 1 Department of Genomic Medicine, St Mary's Hospital, Manchester Academic Health Sciences Centre (MAHSC), Division of Evolution and Genomic Science, University of Manchester, Manchester, UK
  2. 2 Department of Neurosurgery and Neuroradiology Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Manchester Academic Health Sciences Centre (MAHSC), Manchester, UK
  3. 3 Department of Otolaryngology, Manchester Royal Infirmary, Manchester Academic Health Sciences Centre (MAHSC), University of Manchester, Manchester, UK
  4. 4 Department of Neurology, Salford Royal Foundation Trust, Manchester Academic Health Sciences Centre (MAHSC), Manchester, UK
  5. 5 Oxford Centre for Genomic Medicine, Nuffield Orthopaedic Centre, Oxford University Hospitals NHS Trust, Oxford, UK
  6. 6 Department of Neurology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK
  7. 7 Department of Medical Genetics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
  8. 8 Department of Plastic Surgery, Wythenshawe Hospital, Manchester Universities Foundation Trust, Manchester Academic Health Sciences Centre (MAHSC), Manchester, UK
  9. 9 Division of Informatics, Imaging and Data Sciences, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
  1. Correspondence to Dr D Gareth Evans, Department of Genetic Medicine, Manchester Academic Health Sciences Centre (MAHSC), St Mary’s Hospital, University of Manchester, Manchester, M13 9WL, UK; gareth.d.evans{at}manchester.ac.uk

Abstract

Objectives Schwannomatosis is a dominantly inherited condition predisposing to schwannomas of mainly spinal and peripheral nerves with some diagnostic overlap with neurofibromatosis-2 (NF2), but the underlying epidemiology is poorly understood. We present the birth incidence and prevalence allowing for overlap with NF2.

Methods Schwannomatosis and NF2 cases were ascertained from the Manchester region of England (population=4.8 million) and from across the UK. Point prevalence and birth incidence were calculated from regional birth statistics. Genetic analysis was also performed on NF2, LZTR1 and SMARCB1 on blood and tumour DNA samples when available.

Results Regional prevalence for schwannomatosis and NF2 were 1 in 126 315 and 50 500, respectively, with calculated birth incidences of 1 in 68 956 and 1 in 27 956. Mosaic NF2 causes a substantial overlap with schwannomatosis resulting in the misdiagnosis of at least 9% of schwannomatosis cases. LZTR1-associated schwannomatosis also causes a small number of cases that are misdiagnosed with NF2 (1%–2%), due to the occurrence of a unilateral vestibular schwannoma. Patients with schwannomatosis had lower numbers of non-vestibular cranial schwannomas, but more peripheral and spinal nerve schwannomas with pain as a predominant presenting symptom. Life expectancy was significantly better in schwannomatosis (mean age at death 76.9) compared with NF2 (mean age at death 66.2; p=0.004).

Conclusions Within the highly ascertained North-West England population, schwannomatosis has less than half the birth incidence and prevalence of NF2.

  • schwannomatosis
  • LZTR1
  • SMARCB1
  • vestibular schwannoma

https://doi.org/10.1136/jnnp-2018-318538

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    Footnotes

    • Contributors DGE designed the study and carried out the analysis with statistical support from EFH. MJS carried out molecular testing with AJW, NLB, ST and CH. All other authors contributed data or individuals to the study, reviewed the manuscripts and approved the final version.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Patient consent Obtained.

    • Ethics approval Central Manchester Research Ethics Committee.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement Anonymised data from the study are available on request.