Trends in phenotype in the English paediatric neurofibromatosis type 2 cohort stratified by genetic severity. Issue 2 (29th April 2019)

• Record Type: Journal Article
• Authors: Halliday, Dorothy; Emmanouil, Beatrice; Vassallo, Grace; Lascelles, Karine; Nicholson, James; Chandratre, Saleel; Anand, Geetha; Wasik, Martin; Pretorius, Pieter; Evans, D. Gareth; Parry, Allyson
• Other Names: Axon Patrick investigator.; Gair Juliette investigator.; Smyth Carolyn investigator.; Afridi Shazia K investigator.; Obholzer Rupert investigator.; Everett Vanessa investigator.; Jarvis Nicola investigator.; Henshaw Kirsty investigator.; Hanemann C Oliver investigator.; Howard Wendy investigator.; May Anne investigator.; Redman Carolyn investigator.; Rattihalli Rohini investigator.; Tomkins Helen investigator.
• Is Part Of: Clinical genetics. Volume 96:Issue 2(2019)
• Page Start: 151
• Page End: 162
• Publication Date: 2019-04-29
• Subjects: childhood NF2 -- NF2 -- NF2 genetic severity score -- paediatric NF2 genotype phenotype; Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.13551
• Languages: English
• ISSNs: 0009-9163

Abstract

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. Abstract :