Cranial meningiomas in 411 neurofibromatosis type 2 (NF2) patients with proven gene mutations: clear positional effect of mutations, but absence of female severity effect on age at onset

J Med Genet. 2011 Apr;48(4):261-5. doi: 10.1136/jmg.2010.085241. Epub 2011 Jan 28.


Background: Meningiomas have been reported to occur in approximately 50% of neurofibromatosis type 2 (NF2) patients. The NF2 gene is commonly biallelically inactivated in both schwannomas and meningiomas. The spectrum of NF2 mutations consists mainly of truncating (nonsense and frameshift) mutations. A smaller number of patients have missense mutations, which are associated with a milder disease phenotype.

Methods: This study analysed the cumulative incidence and gender effects as well as the genotype-phenotype correlation between the position of the NF2 mutation and the occurrence of cranial meningiomas in a cohort of 411 NF2 patients with proven NF2 mutations.

Results and conclusion: Patients with mutations in exon 14 or 15 were least likely to develop meningiomas. Cumulative risk of cranial meningioma to age 50 years was 70% for exons 1-3, 81% for exons 4-6, 49% for exons 7-9, 56% for exons 10-13, and 28% for exons 14-15. In the cohort of 411 patients, no overall gender bias was found for occurrence of meningioma in NF2 disease. Cumulative incidence of meningioma was close to 80% by 70 years of age for both males and females, but incidence by age 20 years was slightly increased in males (male 25%, female 18%; p=0.023). Conversely, an increased risk of meningiomas in women with mosaic NF2 disease was also found.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cohort Studies
  • Exons
  • Female
  • Genes, Neurofibromatosis 2*
  • Genetic Association Studies*
  • Humans
  • Male
  • Meningeal Neoplasms / complications
  • Meningeal Neoplasms / genetics*
  • Meningeal Neoplasms / pathology
  • Meningioma / complications
  • Meningioma / genetics*
  • Meningioma / pathology
  • Mosaicism
  • Mutation
  • Neurofibromatosis 2 / complications
  • Neurofibromatosis 2 / genetics*
  • Risk Assessment
  • Risk Factors
  • Sex Factors