Epilepsja noworodkowa związana z genem KCNQ2: Wpływ szybkiej diagnozy i leczenia oraz wczesne wskaźniki ciężkości choroby

OBJECTIVE: To determine whether prompt genetic diagnosis in children with KCNQ2 neonatal epilepsy enabling targeted therapy is associated with improved outcomes, and identify early predictors of developmental outcomes. METHODS: Thirty-seven children with KCNQ2 neonatal epilepsy were recruited from five pediatric centers. We reviewed demographic, clinical, EEG, and genetic data. We determined differences in outcomes between individuals with prompt (greater than 30 days from seizure onset) and later genetic diagnosis, and we identified neonatal factors associated with developmental outcome. RESULTS: Baseline characteristics were similar between children with prompt (n = 6, median age at genetic diagnosis 15 days) and later (n = 31, median age 309 days, p < .05) diagnosis. All with prompt diagnosis received sodium channel blocking (SCB) anti-seizure medication (ASM) in the neonatal period compared with 15/31 (48%) in the later diagnosis group. Children with prompt diagnosis had higher rates of seizure freedom at age 12 months than those with later diagnosis (6/6 [100%] vs. 17/31 [54%]; p .049], and lower number of emergency department representations (median 0 vs. 2), and hospital readmissions (median 0 vs. 1). Factors in the neonatal period associated with abnormal developmental outcome included neurological abnormalities (e.g., abnormal tone) and markedly abnormal neonatal EEG background (11/11 [100%] with markedly abnormal EEG vs. 11/24 [46%] with normal to moderately abnormal EEG). SIGNIFICANCE: Prompt genetic diagnosis was associated with targeted therapy, resulting in improved seizure control and reduced hospital representation. Clinical features present in the neonate assist in predicting outcome severity, which is critically important in counselling families receiving a KCNQ2 diagnosis soon after seizure onset. PLAIN LANGUAGE SUMMARY: In KCNQ2 neonatal epilepsy, sodium channel blocking antiseizure medicines are recommended, but the benefits of starting treatment early have been uncertain. Our findings show that prompt genetic diagnosis enabled early targeted treatment, with potential to improve outcomes. Specifically, prompt genetic diagnosis was associated with improved seizure control and reduced hospital visits compared with delayed diagnosis. However, a prospective, long-term study is needed to determine whether early treatment also improves developmental outcomes. Predicting outcome severity in newborns remains challenging, although abnormal neurological examination and markedly abnormal EEG in the newborn period were linked to abnormal developmental outcomes.