Clinical and genetic evaluation of early onset epileptic encephalopathy cases

Objective: Epileptic encephalopathy is defined as epileptic syndromes that cause progressive impairment of cognitive, behavioral and other brain functions. In childhood, these disorders cause a decrease in the developmental process or loss of acquired brain functions. In recent years, genetic causes have begun to be detected more frequently in etiopathogenesis. Pathogenic gene mutations may play a role in the development of epileptic encephalopathy even in the absence of obvious genetic inheritance patterns or kinship. It was aimed to investigate the phenotype-genotype relationship in patients. Method: In the study, 51 genes were studied with a multiple new generation sequencing panel designed for early onset epileptic encephalopathy among 37 patients who were clinically and laboratory pre-diagnosed with early onset epileptic encephalopathy in the Pediatric Neurology Department of Çukurova University Faculty of Medicine, Balcalı Hospital. For the study, causal variants (pathogenic, possibly pathogenic, and VUS) detected in patients were examined. The phenotype-genotype relationship of the patients was evaluated. Results: The preliminary diagnoses of the patients included in the study were West syndrome (n = 24), unclassified early-onset epileptic encephalopathy (n = 8), Ohtahara syndrome (n = 1), and early myoclonic epilepsy (n = 4). Mutation could not be detected in 10 (27 %) of 37 patients. Pathogenic variant was detected in 5 (13,5 %) of the patients. Possible pathogen was detected in 5 patients (13,5 %), and variant with uncertain pathogenicity (VUP) in 7 (19 %) patients. Changes of unknown clinical significance were detected in 10 patients. The causal variant (pathogenic, possible pathogenic and VUP) was detected in 17 (45,9 %) patients in total. In this study, the diagnostic value determined by targeted gene panel analysis containing 51 known epileptic encephalopathy genes was 27 % (P, PP) and 45,9 % (P, PP and VUP). Conclusion: The diagnostic value found in our study was 27 % (P, PP) and 45,9 % (P, PP, and VUP), and was consistent with recent studies using targeted gene panel analyzes in the diagnosis of patients with early onset epileptic encephalopathy. The targeted gene panel is seen as a practical diagnostic tool for early-onset epileptic encephalopathy patients, as it enables genotype-phenotype correlations and guides treatment. Keywords: Epileptic encephalopathy, targeted gene panel, diagnostic value