Przydatność diagnostyczna i predyktory kliniczne sekwencjonowania całego exomu u tajskich dzieci z zaburzeniami rozwojowo-padaczkowymi i padaczką oporną na leki: prospektywne badanie kohortowe

Abstract Developmental and epileptic encephalopathies (DEEs) often have a monogenic basis, but prospective data from Southeast Asia remain limited. We evaluated the diagnostic yield, variant spectrum, and clinical actionability of singleton whole-exome sequencing (WES) — applied as a deliberate first-line strategy in a resource-limited setting — in 117 Thai children younger than 18 years with drug-resistant epilepsy (DRE) and suspected DEE, prospectively enrolled at a tertiary pediatric center between July 2024 and January 2026. Variants were interpreted per American College of Medical Genetics and Genomics guidelines and predictors examined with univariate logistic regression. Pathogenic or likely pathogenic variants were identified in 63 patients (53.8%); ion channel genes predominated, led by SCN1A . Earlier seizure onset ( P = 0.028). Yield was lowest in children with subtle structural imaging abnormalities (11.1%), a clinically useful negative finding for triaging WES allocation. Findings were clinically actionable in 68.3% of diagnosed cases, and median delay from seizure onset to molecular diagnosis was 81 months (IQR 33–131). In this largest prospective Southeast Asian DEE cohort to date, singleton WES — used deliberately as a first-line LMIC strategy — achieved a high diagnostic yield with substantial clinical utility, supporting earlier integration into pediatric epilepsy care across Southeast Asia and similar low- and middle-income settings.