Trends in phenotype in the English paediatric Neurofibromatosis Type 2 cohort stratified by genetic severity

Dorothy Halliday, Beatrice Emmanouil, Grace Vassallo, Karine Lascelles, James Nicholson, Saleel Chandratre, Geetha Anand, Martin Wasik, Pieter Pretorius, D Gareth Evans

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Childhood onset neurofibromatosis type 2 can be severe and genotype dependent. We present a retrospective phenotypic analysis of all ascertained children in England <age 18 (N=87;male 61%). Mean age at last review was 13.9 years with mean follow-up 6.5 years. Patients were stratified using a validated score (1A/1B:no NF2 pathogenic¬_variant in blood; 2A/2B:mild/moderate NF2 constitutional or mosaic pathogenic_variant in blood; 3:constitutional truncating exon 2-13 pathogenic_variant. 91% patients had a constitutional NF2 pathogenic_variant (44% de novo). Mean age at first manifestation was 4.3 and 8.8 years in groups 3 and 2A respectively. Bilateral vestibular schwannoma, intracranial meningioma and spinal schwannoma occurred in 77%, 52% and 65% of group 3 patients respectively, and 58%, 26% and 33% in 2A. 43% group 3 and 18% 2A had severe unilateral visual loss (logmar>1.0). Focal cortical dysplasia occurred in 26% group 3 and 4% 2A. 48% of group 3 underwent ≥1 major intervention (intracranial/spinal surgery/Bevacizumab/radiotherapy) compared to 35% of 2A; with 23% group 3 undergoing spinal surgery (schwannoma/ependymoma/meningioma resection) compared to 4% of 2A. Mean age starting Bevacizumab was 12.7 in group 3 and 14.9 years in 2A. In conclusion, group 3 phenotype manifests earlier with greater tumour load, poorer visual outcomes and more intervention.
Original languageEnglish
JournalClinical Genetics
Early online date16 Apr 2019
Publication statusPublished - 2019


  • NF2
  • , paediatric NF2 genotype phenotype
  • NF2 genetic severity score
  • childhood NF2


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