Evaluation of genetic, electrophysiological and clinical characteristics of patients followed up with the diagnosis of Developmental Epileptic Encephalopathy: A single center experience

Objectives Developmental Epileptic Encephalopathy (DEE) is defined as a group of diseases in which underlying genetic cause leads both developmental delay and epileptic activity.The aim of this study was to evaluate the clinical,electrographic and genetic characteristics of patients with DEE. Methods We retrospectively evaluated 44 consecutive children with monogenic DEE whose genotype-phenotype relationship was shown at the pediatric neurology division of Baskent University,Adana Hospital between 2012-2022. Patients with ALDH7A1,TSC1,TSC2 and SCN1A related DEE, Rett Syndrome and metabolic DEE were excluded as they were a part of different projects. Results Thirty different gene mutations were detected in 44 patients. The mutations were KCNQ2 (n:4),STXBP1(n:3),CACNA1A(n:3),SCN9A(n:3),SCN2A(n:3),CDKL5 (n:2), GABRB3(n:2) and SPTAN1, PLA2G6, KCNB1, EEF1A2, NECAP1, TUBB2A, CHD2, FGF12, ITPA, SIK1, YWHAG, ST3GAL5, FOXG1, PRICKLE2, SCN1B, PCDH19, ATXN2, CACNA1H, PRRT2, ARX, GRIA2, BRAT1, GRIN2D, GABBR2 one each, respectively. Lacosamide response was observed in CHD2 and STXBP1 mutations, folinic acid response in NECAP1 and PRICKLE2 mutations, and pyrimidone response in SCN2A mutation. Conclusions: Advanced genetic studies provide positive contribution to the determination of targeted treatment options and a better understanding of the course of the disease in DEE. Interestingly, the present study showed heterozygous PRICKLE2 mutation in DEE for the first time in the literature. The most important finding of this study is that effective drug therapy,which may be a targeted treatment option,has been reported for the first time for CHD2, STXBP1, NECAP2, PRICKLE2 and SCN2A mutations.
Keywords: monogenic, target therapy, PRICKLE, pyrimidone,lacosamide,folinic acide