Cranial meningiomas in 411 NF2 patients with proven gene mutations: Clear positional effect of mutations, but absence of female severity effect on age at onset

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: We analysed cumulative incidence and gender effects as well as the genotype-phenotype correlation between the position of the NF2 mutation and the occurrence of 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 (risk to 70 years, 37%) and patients with mutations in exons 1-6 were most likely to develop meningiomas (risk to 70 years, 92%). In our cohort of 411 patients, we found no overall gender bias 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 higher in males (male, 25%; female, 18%; p=0.023). Conversely we also found an increased risk of meningiomas in women with mosaic NF2 disease.