{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T14:04:28Z","timestamp":1772114668315,"version":"3.50.1"},"reference-count":16,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,10,16]],"date-time":"2018-10-16T00:00:00Z","timestamp":1539648000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Manchester National Institute for Health Research Biomedical Research Centre"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:sec><jats:title>Objectives\/Hypothesis<\/jats:title><jats:p>Unilateral vestibular schwannoma (VS) occurs with a lifetime risk of around 1 in 1,000 and is due to inactivation of the <jats:italic>NF2<\/jats:italic> 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>Retrospective database analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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\u2010 and second\u2010degree relatives) were assessed for constitutional <jats:italic>NF2<\/jats:italic> and <jats:italic>LZTR1<\/jats:italic> genetic variants, and where possible the tumor was also analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u2010degree 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 <jats:italic>NF2<\/jats:italic> intragenic variant, and in nine cases where the VS was analyzed, both mutational events in <jats:italic>NF2<\/jats:italic> were identified and excluded from the germline. Only three variants of uncertain significance were found in <jats:italic>LZTR1<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Familial occurrence of unilateral VS is very unlikely to be due to a constitutional <jats:italic>NF2<\/jats:italic> or definitely pathogenic <jats:italic>LZTR1<\/jats:italic> variant. The occurrence of unilateral VS in two or more first\u2010degree 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>2b <jats:italic>Laryngoscope<\/jats:italic>, 129:967\u2013973, 2019<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.27554","type":"journal-article","created":{"date-parts":[[2018,10,16]],"date-time":"2018-10-16T12:34:06Z","timestamp":1539693246000},"page":"967-973","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Familial unilateral vestibular schwannoma is rarely caused by inherited variants in the <i>NF2<\/i> gene"],"prefix":"10.1002","volume":"129","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8482-5784","authenticated-orcid":false,"given":"D. Gareth","family":"Evans","sequence":"first","affiliation":[{"name":"Department of Genomic Medicine  Manchester United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew J.","family":"Wallace","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine  Manchester United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Hartley","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine  Manchester United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon R.","family":"Freeman","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology University of Manchester, Manchester Academic Health Science Centre, Division of Evolution and Genomic Sciences, Manchester Universities NHS Foundation Trust  Manchester United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon K.","family":"Lloyd","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology University of Manchester, Manchester Academic Health Science Centre, Division of Evolution and Genomic Sciences, Manchester Universities NHS Foundation Trust  Manchester United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Owen","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of NeuroRadiology Salford Royal NHS Foundation Trust  Salford Manchester United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Axon","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Addenbrooke's Hospital Cambridge  United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte L.","family":"Hammerbeck\u2010Ward","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Salford Royal NHS Foundation Trust  Salford Manchester United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omar","family":"Pathmanaban","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Salford Royal NHS Foundation Trust  Salford Manchester United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott A.","family":"Rutherford","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Salford Royal NHS Foundation Trust  Salford Manchester United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Kellett","sequence":"additional","affiliation":[{"name":"Department of Neurology Salford Royal NHS Foundation Trust  Salford Manchester United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger","family":"Laitt","sequence":"additional","affiliation":[{"name":"Department of NeuroRadiology Salford Royal NHS Foundation Trust  Salford Manchester United 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