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Neonatal-Onset Genetic Epilepsies: A Multicentric Study

Introduction: The most common causes of neonatal seizures are hypoxic ischemic encephalopathies and infections, genetic causes are also important in the etiology. The most common mutations of neonatal onset genetic epilepsy are in the KCNQ2, KCNQ3, SCN2A, SCN8A, KCNT1, CDKL5, SLC25A22, STXBP1 and ARX genes and genotype-phenotype correlations are unclear.

Material-Methods: This multicentric study included 11 pediatric neurology clinics around Turkiye and 60 patients enrolled. The clinical features, electrophysiological and imaging findings, genetic results and treatment responses of the patients were evaluated.

Results: The most common mutations are respectively in the KCNQ2 (13.3%), STXBP1 (6.7%), SCN1A (6.7%) and CDKL5 (5%) genes (Table 1) Genetic diagnoses of the patients were obtained with whole-exome sequencing (63.3%), epilepsy gene panel (20%), single gene analysis (8.3%) and chromosomal microarray analysis (3.3%). Seizure onset time was 9.5±9 days with a median of 5 days. In 5% of patients, the semiology of the dominant seizure was described as non-motor. In electrophysiological studies, different EEG patterns including hypsarrhythmia in STXBP1, IFIH1, GABRB3 mutations, focal/multifocal epileptic activities in SCN1A, ADAM22, PRUNE1 mutations, and multifocal epileptic activities or burst-suppression pattern in CDKL5 mutations were reported.

Conclusions: Genetic causes should be considered in newborns with seizures for the optimal therapeutic choice, especially for gene-specific targeted therapies. Additionally, a better understanding of these entities may help to advance our knowledge regarding prognosis.