[SP3-3A-7] Clinical features and gene mutations analysis in 62 children with early-onset epileptic encephalopathy of unknown causes
Objective:To study the clinical features and gene mutations of early-onset epileptic encephalopathy (EOEE) of unknown causes.
Methods:The clinical data of 62 children diagnosed with unexplained EOEE between June 2013 and June 2015 were obtained and analyzed. Specimens were collected from the selected children and their parents. Next generation sequencing was used to detect epilepsy-related genes.
Results: Among 62 children，male to female ratio is 1.48:1. The average onset age was 3.8±2.2 months. 37 were diagnosed with non-specific EOEE, 17 with West syndrome, 6 with Dravet syndrome, 1 with Ohtahara syndrome, 1 with early myoclonic epileptic encephalopathy (EMEE). Among cases with non-specific EOEE, 3 missense mutations for PCDH19 gene, one frame-shift mutation and one splice site mutation for CDKL5 gene, one denovo nonsense mutation for KCNQ2 gene, and one missense mutation for GRIN2A gene were detected. Among cases with Dravet syndrome, 2 frame-shift mutations, one missense mutation for SCN1A gene, one missense mutation for SCN1A gene, one missense mutation for SCN1A combined with SCN9A gene and one denovo nonsense mutation for STXBP1 gene was detected. After treatment, 22 patients had clinical seizures under control. The child with KCNQ2 gene nonsense mutation was dead.
Conclusions:The clinical phenotypes for children with unexplained EOEE were various. SCN1A、STXBP1、PCDH19、CDKL5 and GRIN2A gene detected in China are in accordance with international countries. The SCN9A gene may be the new pathogenic mutation for Dravet syndrome. And the KCNQ2 gene nonsense mutation may be the lethal mutation.
Methods:The clinical data of 62 children diagnosed with unexplained EOEE between June 2013 and June 2015 were obtained and analyzed. Specimens were collected from the selected children and their parents. Next generation sequencing was used to detect epilepsy-related genes.
Results: Among 62 children，male to female ratio is 1.48:1. The average onset age was 3.8±2.2 months. 37 were diagnosed with non-specific EOEE, 17 with West syndrome, 6 with Dravet syndrome, 1 with Ohtahara syndrome, 1 with early myoclonic epileptic encephalopathy (EMEE). Among cases with non-specific EOEE, 3 missense mutations for PCDH19 gene, one frame-shift mutation and one splice site mutation for CDKL5 gene, one denovo nonsense mutation for KCNQ2 gene, and one missense mutation for GRIN2A gene were detected. Among cases with Dravet syndrome, 2 frame-shift mutations, one missense mutation for SCN1A gene, one missense mutation for SCN1A gene, one missense mutation for SCN1A combined with SCN9A gene and one denovo nonsense mutation for STXBP1 gene was detected. After treatment, 22 patients had clinical seizures under control. The child with KCNQ2 gene nonsense mutation was dead.
Conclusions:The clinical phenotypes for children with unexplained EOEE were various. SCN1A、STXBP1、PCDH19、CDKL5 and GRIN2A gene detected in China are in accordance with international countries. The SCN9A gene may be the new pathogenic mutation for Dravet syndrome. And the KCNQ2 gene nonsense mutation may be the lethal mutation.