title: Mortality associated with neurofibromatosis 1: a cohort study of 1895 patients in 1980-2006 in France.
abstract: BACKGROUND
  Neurofibromatosis 1 (NF1), a common autosomal dominant disorder, was shown in one study to be associated with a 15-year decrease in life expectancy. However, data on mortality in NF1 are limited. Our aim was to evaluate mortality in a large retrospective cohort of NF1 patients seen in France between 1980 and 2006.
  
  
  METHODS
  Consecutive NF1 patients referred to the National French Referral Center for Neurofibromatoses were included. The standardized mortality ratio (SMR) with its 95% confidence interval (CI) was calculated as the ratio of observed over expected numbers of deaths. We studied factors associated with death and causes of death.
  
  
  RESULTS
  Between 1980 and 2006, 1895 NF1 patients were seen. Median follow-up was 6.8 years (range, 0.4-20.6). Vital status was available for 1226 (65%) patients, of whom 1159 (94.5%) survived and 67 (5.5%) died. Overall mortality was significantly increased in the NF1 cohort (SMR, 2.02; CI, 1.6-2.6; P < 10-4). The excess mortality occurred among patients aged 10 to 20 years (SMR, 5.2; CI, 2.6-9.3; P < 10-4) and 20 to 40 years (SMR, 4.1; 2.8-5.8; P < 10-4). Significant excess mortality was found in both males and females. In the 10-20 year age group, females had a significant increase in mortality compared to males (SMR, 12.6; CI, 5.7-23.9; and SMR, 1.8; CI, 0.2-6.4; respectively). The cause of death was available for 58 (86.6%) patients; malignant nerve sheath tumor was the main cause of death (60%).
  
  
  CONCLUSIONS
  We found significantly increased SMRs indicating excess mortality in NF1 patients compared to the general population. The definitive diagnosis of NF1 in all patients is a strength of our study, and the high rate of death related to malignant transformation is consistent with previous work. The retrospective design and hospital-based recruitment are limitations of our study. Mortality was significantly increased in NF1 patients aged 10 to 40 years and tended to be higher in females than in males.
authors.affiliation: AP-HP, Hôpital Henri-Mondor, Service de Dermatologie, F-94010 Créteil, France.
authors.forename: Tu Anh
authors.initials: TA
authors.lastname: Duong
authors.forename: Emilie
authors.initials: E
authors.lastname: Sbidian
authors.forename: Laurence
authors.initials: L
authors.lastname: Valeyrie-Allanore
authors.forename: Cédric
authors.initials: C
authors.lastname: Vialette
authors.forename: Salah
authors.initials: S
authors.lastname: Ferkal
authors.forename: Smaïl
authors.initials: S
authors.lastname: Hadj-Rabia
authors.forename: Christophe
authors.initials: C
authors.lastname: Glorion
authors.forename: Stanislas
authors.initials: S
authors.lastname: Lyonnet
authors.forename: Michel
authors.initials: M
authors.lastname: Zerah
authors.forename: Isabelle
authors.initials: I
authors.lastname: Kemlin
authors.forename: Diana
authors.initials: D
authors.lastname: Rodriguez
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bastuji-Garin
authors.forename: Pierre
authors.initials: P
authors.lastname: Wolkenstein
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005602:France / Q000453:epidemiology; D016514:Genes, Neurofibromatosis 1; D006801:Humans; D008017:Life Expectancy; D008297:Male; D008875:Middle Aged; D018317:Nerve Sheath Neoplasms / Q000150:complications / Q000401:mortality*; D009456:Neurofibromatosis 1 / Q000150:complications* / Q000235:genetics / Q000401:mortality*; D012307:Risk Factors; D055815:Young Adult