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. 2022 Apr;30(4):458-464.
doi: 10.1038/s41431-021-01029-y. Epub 2022 Jan 24.

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

Daniel Moualed  1   2 , Jonathan Wong  3   4 , Owen Thomas  5 , Calvin Heal  6 , Rukhtam Saqib  5 , Cameron Choi  5 , Simon Lloyd  1   7 , Scott Rutherford  8 , Emma Stapleton  1 , Charlotte Hammerbeck-Ward  8 , Omar Pathmanaban  7   8 , Roger Laitt  5 , Miriam Smith  9 , Andrew Wallace  9 , Mark Kellett  10 , Gareth Evans  9 , Andrew King  3   8 , Simon Freeman  11
Affiliations

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

Daniel Moualed et al. Eur J Hum Genet. 2022 Apr.

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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Conflict of interest statement

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

Figures

Fig. 1
Fig. 1
Histogram demonstrating the proportion and number of patients who had undergone treatment to one or both vestibular scwannomas prior to commencement of the study, categorised by Genetic Severity Scale.
Fig. 2
Fig. 2
Histogram demonstrating the prevalence of unilateral or bilateral trigeminal schwannomas, categorised by Genetic Severity Scale.
Fig. 3
Fig. 3
Histogram demonstrating the prevalence of unilateral or bilateral lower cranial nerve schwannomas, categorised by Genetic Severity Scale.
Fig. 4
Fig. 4
Scatterplot demonstrating the mean growth rate of vestibular schwannomas by age-at-study-enrolment, categorised by Genetic Severity Scale.
See this image and copyright information in PMC

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