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. 2019 Apr;129(4):967-973.
doi: 10.1002/lary.27554. Epub 2018 Oct 16.

Familial unilateral vestibular schwannoma is rarely caused by inherited variants in the NF2 gene

D Gareth Evans  1 , Andrew J Wallace  1 , Claire Hartley  1 , Simon R Freeman  2 , Simon K Lloyd  2 , Owen Thomas  3 , Patrick Axon  4 , Charlotte L Hammerbeck-Ward  5 , Omar Pathmanaban  5 , Scott A Rutherford  5 , Mark Kellett  6 , Roger Laitt  3 , Andrew T King  5 , Jemma Bischetsrieder  7 , Jaishri Blakeley  8 , Miriam J Smith  1
Affiliations

Familial unilateral vestibular schwannoma is rarely caused by inherited variants in the NF2 gene

D Gareth Evans et al. Laryngoscope. 2019 Apr.

Abstract

Objectives/hypothesis: Unilateral vestibular schwannoma (VS) occurs with a lifetime risk of around 1 in 1,000 and is due to inactivation of the NF2 gene, either somatically or from a constitutional mutation. It has been postulated that familial occurrence of unilateral VS occurs more frequently than by chance, but no causal mechanism has been confirmed.

Study design: Retrospective database analysis.

Methods: The likelihood of chance occurrence of unilateral VS, or occurring in the context of neurofibromatosis type 2 (NF2), was assessed using national UK audit data and data from the national NF2 database. Families with familial unilateral VS (occurrence in first- and second-degree relatives) were assessed for constitutional NF2 and LZTR1 genetic variants, and where possible the tumor was also analyzed.

Results: Approximately 1,000 cases of unilateral VS occurred annually in the United Kingdom between 2013 and 2016. Of these, 2.5 may be expected to have a first-degree relative who had previously developed a unilateral VS. The likelihood of this occurring in NF2 was considered to be as low as 0.05 annually. None of 28 families with familial unilateral VS had a constitutional NF2 intragenic variant, and in nine cases where the VS was analyzed, both mutational events in NF2 were identified and excluded from the germline. Only three variants of uncertain significance were found in LZTR1.

Conclusions: Familial occurrence of unilateral VS is very unlikely to be due to a constitutional NF2 or definitely pathogenic LZTR1 variant. The occurrence of unilateral VS in two or more first-degree relatives is likely due to chance. This phenomenon may well increase in clinical practice with increasing use of cranial magnetic resonance imaging in older patients.

Level of evidence: 2b Laryngoscope, 129:967-973, 2019.

Keywords: LZTR1; NF2; Unilateral; familial; vestibular schwannoma.

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Figures

Figure 1
Figure 1
Likelihood of familial unilateral vestibular schwannoma in the UK population of 63 million people. FDR = first‐degree relative; FH = family history; NF2 = neurofibromatosis type 2; UVS = unilateral vestibular schwannoma.
See this image and copyright information in PMC

References

    1. Stivaros SM, Stemmer‐Rachamimov AO, Alston R, et al. Multiple synchronous sites of origin of vestibular schwannomas in neurofibromatosis Type 2. J Med Genet 2015;52:557–562 - PMC - PubMed
    1. Evans DGR, Moran A, King A, Saeed S, Gurusinghe N, Ramsden R. Incidence of vestibular schwannoma and neurofibromatosis 2 in the north west of England over a 10 year period: higher incidence than previously thought. Otol Neurotol 2005;26:93–97. - PubMed
    1. Evans DGR, Huson SM, Donnai D, et al. A clinical study of type 2 neurofibromatosis. Q J Med 1992;84:603–618. - PubMed
    1. Smith MJ, Bowers NL, Bulman M, et al. Revisiting neurofibromatosis type 2 diagnostic criteria to exclude LZTR1‐related schwannomatosis. Neurology 2017;88:87–92. - PMC - PubMed
    1. Pathmanaban ON, Sadler KV, Kamaly‐Asl ID, et al. Association of Genetic Predisposition With Solitary Schwannoma or Meningioma in Children and Young Adults. JAMA Neurol 2017;74:1123–1129. - PMC - PubMed

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