Background The clinical severity of disease in neurofibromatosis type 2 (NF2) is variable. Patients affected with a constitutional truncating NF2 mutation have severe disease, while missense mutations or mosaic mutations present with a milder attenuated phenotype. Genotype-derived natural history data are important to inform discussions on prognosis and management.
Methods We have assessed NF2 clinical phenotype in 142 patients in relation to the UK NF2 Genetic Severity Score to validate its use as a clinical and research tool.
Results The Genetic Severity Score showed significant correlations across 10 measures, including mean age at diagnosis, proportion of patients with bilateral vestibular schwannomas, presence of intracranial meningioma, spinal meningioma and spinal schwannoma, NF2 eye features, hearing grade, age at first radiotherapy, age at first surgery and age starting bevacizumab. In addition there was moderate but significant correlation with age at loss of useful hearing, and weak but significant correlations for mean age at death, quality of life, last optimum Speech Discrimination Score and total number of major interventions. Patients with severe disease presented at a younger age had a higher disease burden and greater requirement of intervention than patients with mild and moderate disease.
Conclusions This study validates the UK NF2 Genetic Severity Score to stratify patients with NF2 for both clinical use and natural history studies.
- Neurofibromatosis type 2
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Contributors DH: Study design, acquisition, analysis and interpretation of data and drafting the manuscript. BE: Acquisition, analysis and interpretation of data, revising manuscript critically for intellectual content. PP, SM, SP: Acquisition of data and revising manuscript critically for intellectual content. HT: Acquisition, analysis and interpretation of data. DGE: Interpretation of data and revising manuscript critically for intellectual content. AP: Study design, analysis and interpretation of data, and revising manuscript critically for intellectual content.
Competing interests DGE reports personal fees from Astrazeneca, outside the submitted work.
Patient consent Detail has been removed from this case description/these case descriptions to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.
Ethics approval Study registered as a service evaluation with Oxford University Hospitals Foundation Trust. Registration number: 4406.
Provenance and peer review Not commissioned; externally peer reviewed.
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