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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
  1. Miriam J Smith1,
  2. Jenny E Higgs1,
  3. Naomi L Bowers1,
  4. Dorothy Halliday2,
  5. Joan Paterson3,
  6. James Gillespie4,
  7. Susan M Huson1,
  8. Simon R Freeman5,
  9. Simon Lloyd5,
  10. Scott A Rutherford6,
  11. Andrew T King6,
  12. Andrew J Wallace1,
  13. Richard T Ramsden5,
  14. D Gareth R Evans1
  1. 1Department of Genetic Medicine, St Mary's Hospital, Manchester Academic Health Sciences Centre (MAHSC), University of Manchester, Manchester, UK
  2. 2Department of Clinical Genetics, The Oxford Radcliffe Hospitals NHS Trust, Oxford, UK
  3. 3Department of Medical Genetics, Addenbrookes NHS Trust, Hills Road, Cambridge, UK
  4. 4Department of Neuroradiology, Salford Royal Foundation Trust, Manchester, UK
  5. 5Department of Otolaryngology, Manchester Royal Infirmary, Manchester, UK
  6. 6Department of Neurosurgery, Salford Royal Foundation Trust, Manchester, UK
  1. Correspondence to Professor D Gareth R Evans, Department of Genetic Medicine, St Mary's Hospital, Oxford Road, Manchester M13 9WL, UK; gareth.evans{at}cmft.nhs.uk

Abstract

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.

  • Meningioma
  • NF2
  • Merlin
  • mutation position effect
  • clinical genetics
  • genetic epidemiology

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Footnotes

  • Funding NIHR Manchester Biomedical Research Centre.

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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