Miriam J Smith1, Naomi L Bowers1, Michael Bulman1, Carolyn Gokhale1, Andrew J Wallace1, Andrew T King1, Simon K L Lloyd1, Scott A Rutherford1, Charlotte L Hammerbeck-Ward1, Simon R Freeman1, D Gareth Evans2. 1. 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. 2. 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. gareth.evans@cmft.nhs.uk.
Abstract
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Manish Aghi; Lan Kluwe; Micah T Webster; Lee B Jacoby; Fred G Barker; Robert G Ojemann; Victor-Felix Mautner; Mia MacCollin Journal: J Neurosurg Date: 2006-02 Impact factor: 5.115
Authors: Miriam J Smith; Anjana Kulkarni; Cecilie Rustad; Naomi L Bowers; Andrew J Wallace; Susan E Holder; Arvid Heiberg; Richard T Ramsden; D Gareth Evans Journal: Am J Med Genet A Date: 2011-11-21 Impact factor: 2.802
Authors: K D Hadfield; W G Newman; N L Bowers; A Wallace; C Bolger; A Colley; E McCann; D Trump; T Prescott; D G R Evans Journal: J Med Genet Date: 2008-02-19 Impact factor: 6.318
Authors: Arkadiusz Piotrowski; Jing Xie; Ying F Liu; Andrzej B Poplawski; Alicia R Gomes; Piotr Madanecki; Chuanhua Fu; Michael R Crowley; David K Crossman; Linlea Armstrong; Dusica Babovic-Vuksanovic; Amanda Bergner; Jaishri O Blakeley; Andrea L Blumenthal; Molly S Daniels; Howard Feit; Kathy Gardner; Stephanie Hurst; Christine Kobelka; Chung Lee; Rebecca Nagy; Katherine A Rauen; John M Slopis; Pim Suwannarat; Judith A Westman; Andrea Zanko; Bruce R Korf; Ludwine M Messiaen Journal: Nat Genet Date: 2013-12-22 Impact factor: 38.330
Authors: D Gareth R Evans; Richard T Ramsden; Andrew Shenton; Carolyn Gokhale; Naomi Bowers; Susan M Huson; Andrew J Wallace Journal: J Neurosurg Date: 2008-01 Impact factor: 5.115
Authors: Omar N Pathmanaban; Katherine V Sadler; Ian D Kamaly-Asl; Andrew T King; Scott A Rutherford; Charlotte Hammerbeck-Ward; Martin G McCabe; John-Paul Kilday; Christian Beetz; Nicola K Poplawski; D Gareth Evans; Miriam J Smith Journal: JAMA Neurol Date: 2017-09-01 Impact factor: 18.302
Authors: Rosario Caltabiano; Gaetano Magro; Agata Polizzi; Andrea Domenico Praticò; Andrea Ortensi; Valerio D'Orazi; Andrea Panunzi; Pietro Milone; Luigi Maiolino; Francesco Nicita; Gabriele Lorenzo Capone; Roberta Sestini; Irene Paganini; Mariella Muglia; Sebastiano Cavallaro; Salvatore Lanzafame; Laura Papi; Martino Ruggieri Journal: Childs Nerv Syst Date: 2017-04-01 Impact factor: 1.475
Authors: Hildegard Kehrer-Sawatzki; Lan Kluwe; Reinhard E Friedrich; Anna Summerer; Eleonora Schäfer; Ute Wahlländer; Cordula Matthies; Isabel Gugel; Said Farschtschi; Christian Hagel; David N Cooper; Victor-Felix Mautner Journal: Hum Genet Date: 2018-07-13 Impact factor: 4.132
Authors: Roland Goldbrunner; Michael Weller; Jean Regis; Morten Lund-Johansen; Pantelis Stavrinou; David Reuss; D Gareth Evans; Florence Lefranc; Kita Sallabanda; Andrea Falini; Patrick Axon; Olivier Sterkers; Laura Fariselli; Wolfgang Wick; Joerg-Christian Tonn Journal: Neuro Oncol Date: 2020-01-11 Impact factor: 12.300