Diagnostic yield and treatment impact of whole‐genome sequencing in paediatric neurological disorders

Aim To investigate the diagnostic yield and treatment impact of whole‐genome sequencing (WGS) in patients with paediatric neurological disorders. Method From January 2016 to December 2019, paediatric patients who had suspected genetic neurological disorders were assessed using WGS. The phenotypes of eligible patients were divided into four groups: patients with neurodevelopmental disorders; patients with epilepsy; patients with neuromuscular disorders; and patients with movement disorders. Results A total of 214 consecutive patients (128 males, 86 females) underwent WGS. The mean (SD) age of disease onset was 13.8 (27.6) months (range 1d–15y 5mo). The mean (SD) age at which WGS was performed was 71.7 (58.9) months (range 8d–18y). A molecular diagnosis was reported in 43.9% of patients. The highest diagnostic rate was achieved in 62.5% of patients with neuromuscular disorders, 47.5% of patients with epilepsy, 41.1% of patients with neurodevelopment disorders, and 15.4% of patients with movement disorders. All 94 patients with a WGS diagnosis were given access to genetic counselling and 23.4% of patients had immediate changes in treatment strategies after undergoing WGS. Interpretation WGS allows paediatric neurologists to integrate genomic data into their diagnosis and adjust management strategies for a range of clinical and genetically heterogeneous disease entities to improve the clinical outcomes of patients. In our cohort, the diagnosis of a significant proportion of patients was reached through WGS (43.9%). Clinicians could use these results to directly guide the management of their patients and improve their clinical outcomes (23.4%). What this paper adds For selected children in our cohort, the diagnostic yield of whole‐genome sequencing (WGS) was 43.9%. WGS can be used to expand our knowledge of phenotype–genotype variations. What this paper adds For selected children in our cohort, the diagnostic yield of whole‐genome sequencing (WGS) was 43.9%. WGS can be used to expand our knowledge of phenotype–genotype variations.