Clinical and molecular predictors of mortality in neurofibromatosis 2: a UK national analysis of 1192 patients. Issue 10 (14th August 2015)

• Record Type: Journal Article
• Authors: Hexter, Adam; Jones, Adrian; Joe, Harry; Heap, Laura; Smith, Miriam J; Wallace, Andrew J; Halliday, Dorothy; Parry, Allyson; Taylor, Amy; Raymond, Lucy; Shaw, Adam; Afridi, Shazia; Obholzer, Rupert; Axon, Patrick; King, Andrew T; Friedman, Jan M; Evans, D Gareth R
• Other Names: author non-byline.; Burnet Neil author non-byline.; Donnelly Neil author non-byline.; Durie-Gair Juliette author non-byline.; English Martin author non-byline.; Folland Nicola author non-byline.; Foweraker Karen author non-byline.; Harris Fiona author non-byline.; Harris Frances author non-byline.; Heney David author non-byline.; Jeffries Sarah author non-byline.; Jena Raj author non-byline.; Knight Richard author non-byline.; Lamb Tamara author non-byline.; Macfarlane Robert author non-byline.; Mannion Richard author non-byline.; Nicholson James author non-byline.; Price Richard author non-byline.; Rands Ella author non-byline.; Sanghera Paul author non-byline.; Scoffings Daniel author non-byline.; Tysome James author non-byline.; Ferner Rosalie E author non-byline.; Hammond Chris author non-byline.; Lascelles Karine author non-byline.; Nunn Terry author non-byline.; Saeed Shakeel author non-byline.; Swampillai Angela author non-byline.; Thomson Suki author non-byline.; Walsh Daniel author non-byline.; Williams Victoria author non-byline.; Wood Sue author non-byline.; Anup Raji author non-byline.; Duff Chris author non-byline.; Evans D Gareth author non-byline.; Freeman Simon R author non-byline.; Howie Emma author non-byline.; Huson Susan M author non-byline.; Jarvis Nicola author non-byline.; Kamaly-Asi Ian author non-byline.; King Andrew author non-byline.; Kellett Mark author non-byline.; Kilday John-Paul author non-byline.; Lloyd Simon K author non-byline.; Malluci Connor author non-byline.; Mawman Deborah author non-byline.; McBain Catherine author non-byline.; Mills Sam author non-byline.; O'Driscoll Martin author non-byline.; Patel Sonia author non-byline.; Perry Mary author non-byline.; Rutherford Scott A author non-byline.; Scott-Kitching Vilka author non-byline.; Stivaros Stavros M author non-byline.; Thomas Owen author non-byline.; Vassallo Grace author non-byline.; Ward Charlotte L author non-byline.; Blesing Claire author non-byline.; Cogswell Lucy author non-byline.; Dalton Louise author non-byline.; Dodridge Caroline author non-byline.; Elston John author non-byline.; Giele Henk author non-byline.; Hanemann C Oliver author non-byline.; Howard Wendy author non-byline.; Johnson David author non-byline.; Kerr Richard author non-byline.; Laws Avianna author non-byline.; Lee James author non-byline.; Mace Elle author non-byline.; May Anne author non-byline.; Milford Chris author non-byline.; Pretorius Peter author non-byline.; Ramsden James author non-byline.; Redman Caroline author non-byline.; Warner Nicola author non-byline.; Wilson Shaun author non-byline.;
• Is Part Of: Journal of medical genetics. Volume 52:Issue 10(2015)
• Page Start: 699
• Page End: 705
• Publication Date: 2015-08-14
• Subjects: Neurofibromatosis 2 -- Mortality -- Genotype-phenotype correlation -- Survival; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmedgenet-2015-103290
• Languages: English
• ISSNs: 1468-6244

Abstract

Abstract : Background: Neurofibromatosis 2 (NF2) is an autosomal-dominant tumour predisposition syndrome characterised by bilateral vestibular schwannomas, considerable morbidity and reduced life expectancy. Although genotype–phenotype correlations are well established in NF2, little is known about effects of mutation type or location within the gene on mortality. Improvements in NF2 diagnosis and management have occurred, but their effect on patient survival is unknown. Methods: We evaluated clinical and molecular predictors of mortality in 1192 patients (771 with known causal mutations) identified through the UK National NF2 Registry. Kaplan–Meier survival and Cox regression analyses were used to evaluate predictors of mortality, with jackknife adjustment of parameter SEs to account for the strong intrafamilial phenotypic correlations that occur in NF2. Results: The study included 241 deaths during 10 995 patient-years of follow-up since diagnosis. Early age at diagnosis and the presence of intracranial meningiomas were associated with increased mortality, and having a mosaic, rather than non-mosaic, NF2 mutation was associated with reduced mortality. Patients with splice-site or missense mutations had lower mortality than patients with truncating mutations (OR 0.459, 95% CI 0.213 to 0.990, and OR 0.196, 95% CI 0.213 to 0.990, respectively). Patients with splice-site mutations in exons 6–15 had lower mortality than patients with splice-site mutations in exons 1–5 (OR 0.333, 95% CI 0.129 to 0.858). The mortality of patients with NF2 diagnosed in more recent decades was lower than that of patients diagnosed earlier. Conclusions: Continuing advances in molecular diagnosis, imaging and treatment of NF2-associated tumours offer hope for even better survival in the future.