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Prevalence and natural history of schwannomas in neurofibromatosis type 2 (NF2): the influence of pathogenic variants

European Journal of Human Genetics volume 30, pages 458–464 (2022)Cite this article

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Abstract

This study explores the natural history of vestibular, trigeminal and lower cranial nerve schwannomas (VS, TS, LCNS) in patients with Neurofibromatosis type 2 (NF2), to understand how pathogenic variants (PVs) of the NF2 gene affect tumour burden and growth rate, via a retrospective analysis of a UK NF2 centre database and imaging. VS, TS and LCNS location and size were measured in accordance with a standardised protocol. PVs were categorised in accordance with the UK NF2 Genetic Severity Score (GSS). 153 patients (age 5–82) had 458 schwannomas, of which 362 were previously untreated comprising: 204 VS, 93 TS, and 65 LCNS (IX, X, XI). 322 schwannomas had sequential imaging allowing growth rate analysis with a mean follow-up of 45 months. VS were universally present, and bilateral in 146/153 cases. 65% of tumours grew >2 mm during the study period at mean rate 2.0 mm/year. Significant association was found between increasing GSS and growth rate. TS occurred in 66/153 patients (bilateral in 27/153); 31% of tumours showed growth (mean 1.8 mm/yr). Significant increase in tumour prevalence was noted with increasing GSS. LCNS were found in 47/153 patients (bilateral in 19/153); 27% of tumours showed growth (mean 1.9 mm/yr). The trend for increased prevalence with increasing GSS did not reach significance. VS growth rate was significantly influenced by GSS and they were much more likely to grow than TS and LCNS. TS prevalence also correlated with increasing GSS.

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Data availability

The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Otolaryngology, Manchester University NHS Foundation Trust, Manchester, UK

    Daniel Moualed, Simon Lloyd, Emma Stapleton & Simon Freeman

  2. Department of Otolaryngology, Great Western Hospitals NHS Foundation Trust, Swindon, UK

    Daniel Moualed

  3. The University of Manchester, Manchester, UK

    Jonathan Wong & Andrew King

  4. Department of Otolaryngology, Tan Tock Seng Hospital, Singapore, Singapore

    Jonathan Wong

  5. Department of Neuroradiology, Salford Royal NHS Foundation Trust, Salford, UK

    Owen Thomas, Rukhtam Saqib, Cameron Choi & Roger Laitt

  6. Centre for Biostatistics, The University of Manchester, Manchester, UK

    Calvin Heal

  7. Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK

    Simon Lloyd & Omar Pathmanaban

  8. Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Salford, UK

    Scott Rutherford, Charlotte Hammerbeck-Ward, Omar Pathmanaban & Andrew King

  9. Genomic Medicine, The University of Manchester, Manchester, UK

    Miriam Smith, Andrew Wallace & Gareth Evans

  10. Department of Neurology, Manchester University NHS Foundation Trust, Manchester, UK

    Mark Kellett

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Contributions

Study conception and design: SRF, JW, OT, SKL, SAR, ES, CHW, ONP, RL, MJS, AJW, MK, DGE, and ATK. Data collection: DM, JW, OT, RS, CC, RL, and SRF. Data analysis: DM, JW, OT, CH, and SRF. Results interpretation: SRF, DM, JW, OT, SKL, SAR, ES, CHW, ONP, RL, MJS, AJW, MK, DGE, and ATK. Drafting the manuscript: DM, and JW. Manuscript revision and approval: all authors.

Corresponding author

Correspondence to Simon Freeman.

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Competing interests

DGE, SKL and MJS are supported by the all Manchester NIHR Biomedical Research Centre (IS-BRC-1215-20007). The authors declare no competing interests.

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Moualed, D., Wong, J., Thomas, O. et al. Prevalence and natural history of schwannomas in neurofibromatosis type 2 (NF2): the influence of pathogenic variants. Eur J Hum Genet 30, 458–464 (2022). https://doi.org/10.1038/s41431-021-01029-y

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