Trends in phenotype in the English paediatric neurofibromatosis type 2 cohort stratified by genetic severity.

Abstract

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. A total of 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. A total of 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. A total of 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.

• Authors: Dorothy Halliday, Beatrice Emmanouil, Grace Vassallo, Karine Lascelles, James Nicholson, Saleel Chandratre, Geetha Anand, Martin Wasik, Pieter Pretorius, D Gareth Evans, Allyson Parry, English NF2 research group
• Journal: Clinical genetics (Clin Genet) Vol. 96 Issue 2 Pg. 151-162 (08 2019) ISSN: 1399-0004 [Electronic] Denmark
• PMID: 30993672 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Topics

• Adolescent
• Child
• Combined Modality Therapy
• Disease Management
• Exons
• Follow-Up Studies
• Genetic Association Studies (methods)
• Genetic Predisposition to Disease
• Humans
• Magnetic Resonance Imaging
• Neurofibromatosis 2 (diagnosis, genetics, therapy)
• Phenotype
• Severity of Illness Index