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

Abstract

<jats:title>Abstract</jats:title><jats:p>Childhood onset neurofibromatosis type 2 can be severe and genotype dependent. We present a retrospective phenotypic analysis of all ascertained children in England &lt;age 18 (<jats:italic>N</jats:italic> = 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 <jats:italic>NF2</jats:italic> pathogenic_variant in blood; 2A/2B:mild/moderate <jats:italic>NF2</jats:italic> constitutional or mosaic pathogenic_variant in blood; 3: constitutional truncating exon 2‐13 pathogenic_variant. A total of 91% patients had a constitutional <jats:italic>NF2</jats:italic> 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 &gt;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.</jats:p>