ena-STUDY-SEOUL NATIONAL UNIVERSITY COLLEGE OF MEDICINE-03-05-2018-01:13:29:524-44
Diagnostic yield of epilepsy panel testing of patients with seizure onset within the first year of life
Objective: Although epilepsy gene panel testing is increasingly used clinically, its diagnostic yield varies widely. Studies suggest that earlier seizure onset may be linked to higher diagnostic rates. Thus, we aimed to evaluate the diagnostic yield of epilepsy gene panel testing of epilepsy patients whose seizures began within the first year after birth.Methods: We included 112 patients with seizure onset before 12 months and no known etiology. Deep targeted sequencing with custom-designed capture probe was performed to ensure detection of germline or mosaic sequence variants and copy number variations (CNVs). Results: We identified pathogenic, or likely pathogenic, variants in 54 patients (48.2%, 54/112), including five with pathogenic CNVs. Two putative pathogenic mosaic variants in SCN8A and KCNQ2 were also detected and validated. Those with neonatal onset (61.5%, 16/26) and early infantile onset (51.7%, 30/58) showed higher diagnostic rates than those with late infantile onset (28.5%, 8/28). Diagnostic rate was similar between patients with a specific syndrome (53.8%,28/52) and those with no recognizable syndrome (43.3%, 26/60).Significance: Genetic cause was identified in nearly half of infantile onset epilepsy patients through epilepsy gene panel testing. Since the phenotypic spectrum is expanding, and characterizing it at seizure onset is difficult, this group should be prioritized for epilepsy gene panel testing.
Objective: Although epilepsy gene panel testing is increasingly used clinically, its diagnostic yield varies widely. Studies suggest that earlier seizure onset may be linked to higher diagnostic rates. Thus, we aimed to evaluate the diagnostic yield of epilepsy gene panel testing of epilepsy patients whose seizures began within the first year after birth.Methods: We included 112 patients with seizure onset before 12 months and no known etiology. Deep targeted sequencing with custom-designed capture probe was performed to ensure detection of germline or mosaic sequence variants and copy number variations (CNVs). Results: We identified pathogenic, or likely pathogenic, variants in 54 patients (48.2%, 54/112), including five with pathogenic CNVs. Two putative pathogenic mosaic variants in SCN8A and KCNQ2 were also detected and validated. Those with neonatal onset (61.5%, 16/26) and early infantile onset (51.7%, 30/58) showed higher diagnostic rates than those with late infantile onset (28.5%, 8/28). Diagnostic rate was similar between patients with a specific syndrome (53.8%,28/52) and those with no recognizable syndrome (43.3%, 26/60).Significance: Genetic cause was identified in nearly half of infantile onset epilepsy patients through epilepsy gene panel testing. Since the phenotypic spectrum is expanding, and characterizing it at seizure onset is difficult, this group should be prioritized for epilepsy gene panel testing.