[SP3-3A-6] Clinical features and targeted sequencing of early epileptic encephalopathies patients with unknown cause
[Introduction] Early epileptic encephalopathies (EEEs）are a devastating group of pediatric epilepsies occurring during the neonatal or infantile periods, which characterized by refractory seizures, psychomotor development impairment or regression associated with ongoing epileptic activity.
[Objective] To analyze the clinical features of idiopathic EEEs patients without causative copy number variants, and to explore the etiology of EEEs by captured sequencing.
[Methods] We perform targeted capture and next generation sequencing 208 genes, followed by bioinformatics analysis and Sanger sequencing to identify pathogenic and or likely-pathogenic mutations.
[Results] Among 58 EEEs patients with unknown cause, 44 were diagnosed with West syndrome, 4 with Dravet syndrome, 2 with Ohtahara syndrome and 8 with unclassified early epileptic encephalopathy. 31% patients had brain dysplasia or astrophy, 60% of patients were normal. 24 patients responded effectively to treatment, 26 patients were resistant to treatment, 3 patients died, 5 patients were lost to follow up. We identified 9 pathogenic mutations in 10 patients, 8 of which were de novo, including mutations of CDKL5 (n=2), STXBP1 (n=1), SCN1A (n=3), KCNQ2 (n=1), SCN8A (n=1), STXBP1 (n=1) and ARX (n=1). Additionally, three likely-pathogenic mutations including mutations of SCN1A (n=2) and KCNQ2 (n=1), but parental testing were not applicable.
[Significance] This research not only enriched the gene bank of EEEs, but also improved the understanding of the clinical characteristic and possible etiology of EEEs, thereby provide clues for genetic counseling for these family.
[Objective] To analyze the clinical features of idiopathic EEEs patients without causative copy number variants, and to explore the etiology of EEEs by captured sequencing.
[Methods] We perform targeted capture and next generation sequencing 208 genes, followed by bioinformatics analysis and Sanger sequencing to identify pathogenic and or likely-pathogenic mutations.
[Results] Among 58 EEEs patients with unknown cause, 44 were diagnosed with West syndrome, 4 with Dravet syndrome, 2 with Ohtahara syndrome and 8 with unclassified early epileptic encephalopathy. 31% patients had brain dysplasia or astrophy, 60% of patients were normal. 24 patients responded effectively to treatment, 26 patients were resistant to treatment, 3 patients died, 5 patients were lost to follow up. We identified 9 pathogenic mutations in 10 patients, 8 of which were de novo, including mutations of CDKL5 (n=2), STXBP1 (n=1), SCN1A (n=3), KCNQ2 (n=1), SCN8A (n=1), STXBP1 (n=1) and ARX (n=1). Additionally, three likely-pathogenic mutations including mutations of SCN1A (n=2) and KCNQ2 (n=1), but parental testing were not applicable.
[Significance] This research not only enriched the gene bank of EEEs, but also improved the understanding of the clinical characteristic and possible etiology of EEEs, thereby provide clues for genetic counseling for these family.