Lin Yang1,2, Yanting Kong3, Xinran Dong2, Liyuan Hu3, Yifeng Lin2, Xiang Chen3, Qi Ni2, Yulan Lu2, Bingbing Wu2, Huijun Wang2, Q Richard Lu4, Wenhao Zhou5,6,7. 1. Clinical Genetic Center, Children's Hospital of Fudan University, Shanghai, China. 2. Key Laboratory of Birth Defects, Children's Hospital of Fudan University, Shanghai, China. 3. Division of Neonatology, Children's Hospital of Fudan University, Shanghai, China. 4. Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. richard.lu@cchmc.org. 5. Key Laboratory of Birth Defects, Children's Hospital of Fudan University, Shanghai, China. zwhchfu@126.com. 6. Division of Neonatology, Children's Hospital of Fudan University, Shanghai, China. zwhchfu@126.com. 7. Key Laboratory of Neonatal Diseases, Ministry of Health, Children's Hospital of Fudan University, Shanghai, China. zwhchfu@126.com.
Abstract
PURPOSE: Genetic diagnosis for children suffering from epilepsy has important implications for treatment, prognosis, and development of precision medicine strategies. METHODS: We performed exome sequencing (ES) or targeted sequencing on 733 children with epilepsy onset within the first year of life. We subgrouped our patients based on the onset age of seizure into neonatal and before 1 year (1-12 months), to compare the clinical and genetic features. RESULTS: The subgroups with different onset age of seizure showed different pathogenic variant spectrum, and the 1-year age group was more likely to have developmental delays than the neonate group (p = 0.000614). The diagnostic rate was 26.7% for targeted sequencing using a 2742-gene panel, and 42% for ES. We identified 12 genes, which covered 48.7% of diagnostic cases. Our data revealed that 41.9% of patients in the neonate group and 49.7% patients in the 1-year group had treatment options based on molecular diagnosis. CONCLUSION: The 12 most commonly implicated genes in this cohort and the genes with treatment options should be considered as part of the essential panel for early diagnosis of epilepsy onset, if large medical exome analyses or ES are not feasible as first-tier analysis. Genetic results are beginning to improve therapy by antiepileptic medication selections and precision medicine approaches.
PURPOSE: Genetic diagnosis for children suffering from epilepsy has important implications for treatment, prognosis, and development of precision medicine strategies. METHODS: We performed exome sequencing (ES) or targeted sequencing on 733 children with epilepsy onset within the first year of life. We subgrouped our patients based on the onset age of seizure into neonatal and before 1 year (1-12 months), to compare the clinical and genetic features. RESULTS: The subgroups with different onset age of seizure showed different pathogenic variant spectrum, and the 1-year age group was more likely to have developmental delays than the neonate group (p = 0.000614). The diagnostic rate was 26.7% for targeted sequencing using a 2742-gene panel, and 42% for ES. We identified 12 genes, which covered 48.7% of diagnostic cases. Our data revealed that 41.9% of patients in the neonate group and 49.7% patients in the 1-year group had treatment options based on molecular diagnosis. CONCLUSION: The 12 most commonly implicated genes in this cohort and the genes with treatment options should be considered as part of the essential panel for early diagnosis of epilepsy onset, if large medical exome analyses or ES are not feasible as first-tier analysis. Genetic results are beginning to improve therapy by antiepileptic medication selections and precision medicine approaches.