An overview of drug-resistant epilepsies based on advances in genetics: a cohort study

Objectives: Etiology of drug-resistant epilepsy (DRE) is multifactorial. Small proportion of affected patients are diagnosed with genetics. Nowadays, specific gene panels and whole exome squencing (WES) have increased the opportunities for specific diagnosis and treatments with developments in genetics. In this cohort study, we determined the specific diagnostic value of gene panels and WES analysis in our cases followed up with the diagnosis of DRE. Methods: The medical records of 2897 cases were reviewed. The clinical features, and genetic results of the cases that had True Sight One panel (130 cases) and WES examination (303 cases) followed up by DRE, were evaluated. Results: Significant pathogenic mutations were detected in 105 (34.6%) of 303 patients who underwent WES. The original diagnosis was made in 25 (19.2%) of 130 cases in which the True Sight One panel was studied. Significant mutations (30%) were detected in 130 of 433 patients. Pathogenic mutations were detected most frequently in SCN1A (n= 13), CDKL5 (n=7) and STXBP1(n= 5) genes. Afterwards, significant pathogenic changes were found in MECP2, TREX1, CACNA1H, PRUNE1, CLP1, PNKP, TPP1, KCTD7, CLN6, CLN8, GRIN2A, SLC2A1, FLNA, SCN8A, SCN9A, UBE3A, WWOX, KCNQ2, PRICKLE2 genes. Conclusion: Despite detecting the increasing number of DRE-associated genes, the clinical features of these disorders often overlap and are difficult to make a systematic diagnosis. Genetic tests especially whole exome sequence analysis significantly, increase the rate of original diagnosis in DRE cases. Definite genetic diagnosis is very important in terms of avoiding unnecessary tests, choosing specific treatment and genetic counseling.
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