Early Onset Epileptic Encephalopathy: Genetic Analysis and Further Delineation of Genotype-phenotype Correlation

Objective: Early onset epileptic encephalopathy (EOEE)remains an important diagnostic and therapeutic challenge.The objective was to perform genetic analysis in patientswith EOEE and to further delineate the genotype-phenotype correlation in patients with EOEE. Methods: We recruited 15 refractory epileptic patientswith epileptic onset before age 12 months. All patients had metabolic screening, electroencephalogram, magnetic reso-nance imaging and molecular analysis (comparative genomic hybridization, gene sequencing, next generation sequencing and or whole exome sequencing. Results: Dravet syndrome (DS) with SCN1A mutations was found in six patients with refractory epilepsy (RE) andmoderate to severe developmental delay (DD). Two patients diagnosed (KCNT1, SCN) with malignant migrating partialseizure (MMPS) had RE, severe DD, autistic behavior. The latter had movement disorders (video) (choreoathetosis, ballis-mus) with a worse outcome than the patients with DS phe-notype with SCN1A mutations. Severe DD and RE wasfound in patients with SCN8A, SLC13A5, SMC1A, orHCFC1 and ATRX mutations. Patient with SCN2A mutation had severe DD. A better outcome was observed in the patient with CDKL5 mutations in the catalytic domain in compari-son with the patient with a deletion in Xp22.13 including CDKL5. The patient with SMC1A mutations disclosed the Cornelia de Lange syndrome phenotype (Table 1). TRXmutations and deletions in 2q24.3 and Xp22.13. In SLC13A5 and SCN2A mutations, epileptic onset occurred atthe earliest age.