Smith Miriam J, Bowers Naomi L, Bulman Michael, Gokhale Carolyn, Wallace Andrew J, King Andrew T, Lloyd Simon K L, Rutherford Scott A, Hammerbeck-Ward Charlotte L, Freeman Simon R, Evans D Gareth
From the Centre for Genomic Medicine, Division of Evolution and Genomic Science, School of Biological Sciences, St Mary's Hospital (M.J.S., N.L.B., M.B., C.G., A.J.W., D.G.E.), Department of Otolaryngology, Manchester Royal Infirmary (S.K.L.L., S.R.F.), and the Department of Neurosurgery, Salford Royal Foundation Trust (A.T.K., S.A.R., C.L.H.-W.), Manchester Academic Health Sciences Centre, University of Manchester, UK.
Neurology. 2017 Jan 3;88(1):87-92. doi: 10.1212/WNL.0000000000003418. Epub 2016 Nov 16.
To determine the specificity of the current clinical diagnostic criteria for neurofibromatosis type 2 (NF2) relative to the requirement for unilateral vestibular schwannoma (VS) and at least 2 other NF2-related tumors.
We interrogated our Manchester NF2 database, which contained 205 individuals meeting NF2 criteria who initially presented with a unilateral VS. Of these, 83 (40.7%) went on to develop a contralateral VS. We concentrated our genetic analysis on a group of 70 who initially fulfilled NF2 criteria with a unilateral vestibular schwannoma and at least 2 additional nonintradermal schwannomas.
Overall, 5/70 (7%) individuals with unilateral VS and at least 2 other schwannomas had a pathogenic or likely pathogenic LZTR1 mutation. Twenty of the 70 subsequently developed bilateral disease. Of the remaining 50, 5 (10%) had a germline LZTR1 mutation, equivalent to the number (n = 5) with a germline NF2 mutation.
The most common etiology for unilateral VS and 2 additional NF2-associated tumors in this cohort was mosaic NF2. Germline LZTR1 and germline NF2 mutations were equally common in our cohort. This indicates that LZTR1 must be considered when making a diagnosis of NF2 in the presence of unilateral VS in individuals without a germline NF2 mutation.
确定2型神经纤维瘤病（NF2）当前临床诊断标准相对于单侧前庭神经鞘瘤（VS）及至少2种其他NF2相关肿瘤要求的特异性。
我们查询了曼彻斯特NF2数据库，该数据库包含205名符合NF2标准且最初表现为单侧VS的个体。其中，83例（40.7%）随后发生了对侧VS。我们将基因分析集中在一组70名最初符合NF2标准、患有单侧前庭神经鞘瘤且至少有2种额外非皮内神经鞘瘤的个体上。
总体而言，5/70（7%）患有单侧VS且至少有2种其他神经鞘瘤的个体存在致病性或可能致病性的LZTR1突变。70例中有20例随后发展为双侧疾病。在其余50例中，5例（10%）有生殖系LZTR1突变，与有生殖系NF2突变的数量（n = 5）相当。
该队列中单侧VS及另外2种NF2相关肿瘤最常见的病因是嵌合型NF2。在我们的队列中，生殖系LZTR1和生殖系NF2突变同样常见。这表明在对无生殖系NF2突变且存在单侧VS的个体进行NF2诊断时，必须考虑LZTR1。
