Analysis on clinical phenotypes and genetic variations of 21 pediatric patients with neonatal seizures of unknown causes

CUI Qingyang; ZHAO Haihai; WANG Weiwei; LI Zhenzhen; SHANG Yun; SUN Yazhou; HUANG Shuixia

doi:10.3969/j.issn.1674-3806.2025.10.14

Abstract：Objective To analyze the clinical phenotypes and genetic variation characteristics of 21 pediatric patients with neonatal seizures of unknown causes.Methods A retrospective analysis was conducted on the clinical data of 21 pediatric patients with neonatal seizures of unknown causes who were admitted to Department of Neonatology,the First Affiliated Hospital of Xinxiang Medical University and Department of Neonatology,Luoyang Maternal and Child Health Hospital from September 2018 to October 2024.The results of blood tandem mass spectrometry,urine gas chromatography-mass spectrometry and whole exome gene detection were analyzed,and the clinical outcomes of the pediatric patients were summarized.Results In the 21 pediatric patients,7 pediatric patients were male and 14 pediatric patients were female.All of the pediatric patients presented with seizures as the initial manifestation.There were no abnormalities in the blood tandem mass spectrometry and urine gas chromatography-mass spectrometry.Head magnetic resonance imaging(MRI)indicated that there were no abnormalities or the abnormal results were not specific.The results of 24-hour video electroencephalography(EEG)in all the pediatric patients showed abnormalities,mainly including sharp waves,spike waves and slow waves,with a few abnormalities showing burst-inhibition.The genetic testing results in the 21 pediatric patients were positive.There were 7 cases of benign familial neonatal seizures caused by variations in KCNQ2,KCNQ3 and SCN2A genes,and 12 cases of developmental and epileptic encephalopathies caused by variations in KCNA2,KCNQ2,CNPY3,ATP6V1A and MT-ND3 genes.Two pediatric patients with variations in KCNQ2 gene were lost to follow-up and their clinical phenotypes could not be determined.The follow-up was conducted until April 2025.Two pediatric patients were lost to follow up.Seven pediatric patients died,all of whom were pediatric patients with developmental and epileptic encephalopathies.Conclusion Genetic testing is helpful for judging the prognosis of neonatal seizures.This study reveals that variations in CNPY3 and ATP6V1A genes lead to developmental and epileptic encephalopathies,which enriches the disease gene spectrum.