講演情報
[OE4-2]生後3年以内にてんかん発作を発症した小児の分子診断状況
○西口 礼子1, Swaroop Aradhya2, Lauren DeRienzo3, Celene Grayson3, Britt Johnson2, Dee Mcknight2, Ana Morales2, Robin Sherrington3, Andrew Wilcock3, Heather Mclaughlin2 (1.インヴィティ ジャパン株式会社グローバルメディカルアフェアーズ部, 2.Invitae Corporation, San Francisco, USA, 3.Xenon Pharmaceuticals, Inc., Burnaby, Canada)
Background: The molecular diagnostic landscape of children with epilepsy is poorly understood. Behind The Seizure (BTS), a sponsored no-charge genetic testing program, was initiated to accelerate molecular diagnoses in this cohort.
Methods: Exon sequencing and copy number evaluation was performed on up to 302 epilepsy associated genes. Clinical history including seizure type and onset, family history, developmental delays, and use of anti-seizure medications was collected. Molecular diagnostic yield analyses were performed for various ages at seizure onset. Time to molecular diagnosis was determined for the top 10 genes in each seizure onset category.
Results: A total of 15,074 individuals with seizure-onset in the first 36 months of life were tested between 2019 to 2022. The most common molecular diagnoses varied substantially according to age at seizure onset. KCNQ2 was the predominant molecular diagnostic finding in neonates with seizure onset at ＜1month, KCNQ2 and CDKL5 predominated in infants with seizure onset between 1-2 months, and PRRT2 and SCN1A were the most prevalent diagnostic findings for infants with seizure onset between both 3-5 months and 6-11 months. SCN1A was the most common molecular diagnostic finding in children with seizure onset between 12-36 months. The median time to molecular diagnosis varied, based by gene.
Conclusions: These data provide a better understanding of the molecular diagnostic landscape of children with seizure onset in the first three years of life and emphasize the importance of broad and early testing in children with epilepsy.
Methods: Exon sequencing and copy number evaluation was performed on up to 302 epilepsy associated genes. Clinical history including seizure type and onset, family history, developmental delays, and use of anti-seizure medications was collected. Molecular diagnostic yield analyses were performed for various ages at seizure onset. Time to molecular diagnosis was determined for the top 10 genes in each seizure onset category.
Results: A total of 15,074 individuals with seizure-onset in the first 36 months of life were tested between 2019 to 2022. The most common molecular diagnoses varied substantially according to age at seizure onset. KCNQ2 was the predominant molecular diagnostic finding in neonates with seizure onset at ＜1month, KCNQ2 and CDKL5 predominated in infants with seizure onset between 1-2 months, and PRRT2 and SCN1A were the most prevalent diagnostic findings for infants with seizure onset between both 3-5 months and 6-11 months. SCN1A was the most common molecular diagnostic finding in children with seizure onset between 12-36 months. The median time to molecular diagnosis varied, based by gene.
Conclusions: These data provide a better understanding of the molecular diagnostic landscape of children with seizure onset in the first three years of life and emphasize the importance of broad and early testing in children with epilepsy.