Ji-Hoon Na1, Saeam Shin2, Donghwa Yang1, Borahm Kim2, Heung Dong Kim1, Sehee Kim1, Joon-Soo Lee1, Jong-Rak Choi2, Seung-Tae Lee3, Hoon-Chul Kang4. 1. Divison of Pediatric Neurology, Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine, Epilepsy Research Institute, Seoul, South Korea. 2. Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, South Korea. 3. Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, South Korea. Electronic address: lee.st@yuhs.ac. 4. Divison of Pediatric Neurology, Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine, Epilepsy Research Institute, Seoul, South Korea. Electronic address: HIPO0207@yuhs.ac.
Abstract
BACKGROUND: Early-onset developmental and epileptic encephalopathy (DEE) is characterized by repeated seizures beginning within 3 months of birth and severe interictal epileptiform discharge, including burst suppression. This study assessed the utility of targeted gene panel sequencing in the genetic diagnosis of this disease. MATERIALS AND METHODS: Targeted gene panel sequencing was performed in 150 early infantile-onset DEE patients (≤3 months of age), and we extensively reviewed their clinical characteristics, including therapeutic efficacy, according to genotype. RESULTS: Of the early infantile-onset DEE patients, 70 were neonatal-onset DEE and the other 80 patients began experiencing seizures from 1 to 3 months after birth. There were 11 different pathogenic or likely pathogenic variants among 34.7% (52/150) of patients with early infantile-onset DEE, in whom KCNQ2, STXBP1, CDKL5, and SCN1A were the major pathogenic variants. Among the neonatal-onset DEE patients, pathological genes were identified in 42.9% (30/70), indicating a significantly higher diagnostic yield than in 27.5% (22/80) of patients who experienced seizure onset 1 to 3 months after birth (p = 0.048). Among the neonatal-onset DEE group, variants in KCNQ2, STXBP1, and CDKL5 were detected at high frequencies, accounting for 66.7% (20/30) of the pathogenic or likely pathogenic variants found in this study. CONCLUSION: Targeted gene panel sequencing demonstrated a high yield of pathogenic variants in the diagnosis of early-onset epileptic encephalopathy, especially in those with neonatal-onset DEE. Early diagnosis of early-onset epileptic encephalopathy may improve the prognosis of patients by earlier selection of appropriate treatment based on pathogenic variant.
BACKGROUND: Early-onset developmental and epileptic encephalopathy (DEE) is characterized by repeated seizures beginning within 3 months of birth and severe interictal epileptiform discharge, including burst suppression. This study assessed the utility of targeted gene panel sequencing in the genetic diagnosis of this disease. MATERIALS AND METHODS: Targeted gene panel sequencing was performed in 150 early infantile-onset DEE patients (≤3 months of age), and we extensively reviewed their clinical characteristics, including therapeutic efficacy, according to genotype. RESULTS: Of the early infantile-onset DEE patients, 70 were neonatal-onset DEE and the other 80 patients began experiencing seizures from 1 to 3 months after birth. There were 11 different pathogenic or likely pathogenic variants among 34.7% (52/150) of patients with early infantile-onset DEE, in whom KCNQ2, STXBP1, CDKL5, and SCN1A were the major pathogenic variants. Among the neonatal-onset DEE patients, pathological genes were identified in 42.9% (30/70), indicating a significantly higher diagnostic yield than in 27.5% (22/80) of patients who experienced seizure onset 1 to 3 months after birth (p = 0.048). Among the neonatal-onset DEE group, variants in KCNQ2, STXBP1, and CDKL5 were detected at high frequencies, accounting for 66.7% (20/30) of the pathogenic or likely pathogenic variants found in this study. CONCLUSION: Targeted gene panel sequencing demonstrated a high yield of pathogenic variants in the diagnosis of early-onset epileptic encephalopathy, especially in those with neonatal-onset DEE. Early diagnosis of early-onset epileptic encephalopathy may improve the prognosis of patients by earlier selection of appropriate treatment based on pathogenic variant.
Authors: William Hong; Isabel Haviland; Elia Pestana-Knight; Judith L Weisenberg; Scott Demarest; Eric D Marsh; Heather E Olson Journal: CNS Drugs Date: 2022-05-28 Impact factor: 6.497
Authors: Dina Simkin; Christina Ambrosi; Kelly A Marshall; Luis A Williams; Jordyn Eisenberg; Mennat Gharib; Graham T Dempsey; Alfred L George; Owen B McManus; Evangelos Kiskinis Journal: Trends Pharmacol Sci Date: 2022-05 Impact factor: 17.638
Authors: Priscilla D Negraes; Cleber A Trujillo; Nam-Kyung Yu; Wei Wu; Hang Yao; Nicholas Liang; Jonathan D Lautz; Ellius Kwok; Daniel McClatchy; Jolene Diedrich; Salvador Martinez de Bartolome; Justin Truong; Ryan Szeto; Timothy Tran; Roberto H Herai; Stephen E P Smith; Gabriel G Haddad; John R Yates; Alysson R Muotri Journal: Mol Psychiatry Date: 2021-04-22 Impact factor: 15.992