Detection of Deregulated miRNAs in Childhood Epileptic Encephalopathies

Aims The term "epileptic encephalopathy" is used to describe a possible relationship between epilepsy and developmental delay. The pathogenesis of developmental encephalopathies, independent of epilepsy, can be defined by genetic control mechanisms. The aim of this study was to investigate the use of miRNAs as serum biomarkers for the determination and discrimination of epileptic encephalopathies. Methods Whole blood samples obtained from 54 individuals in 2 groups designated as epileptic encephalopathy patients group (n=24) and healthy controls (n=30) were included in this study. The expression levels of 10 miRNAs were determined using qRT-PCR. After the determination of expression levels the correlation of upregulated miRNA levels and Ki67 index was calculated using Pearson correlation test. Results The comparison of epileptic encephalopathy patients group with healthy controls revealed the upregulation of one miRNAs (hsa-miR-324-5p) and downregulation of three miRNAs (hsa-miR-146a-5p, hsa-miR-138-5p, hsa-miR-187-3p). Conclusion It has been determined that miRNAs with altered expression are an important factor in the formation of epileptic seizures and seizure-induced neuronal death. The fact that processes that play a key role in epiloptogenesis are under the control of miRNAs causes miRNAs to become meta-controllers of gene expression in the brain. We thouhgt that further studies are needed to prove that especially, hsa-miR-146a-5p, hsa-miR-138-5p and hsa-miR-187-3p can be used as epileptic encephalopathy biomarkers. Detection of disease-specific miRNAs could contribute to the development of presicion treatments.

Inherited Developmental and Epileptic Encephalopathies

Epileptic encephalopathies often have a genetic etiology. The epileptic activity itself exerts a direct detrimental effect on neurodevelopment, which may add to the cognitive impairment induced by the underlying mutation (“developmental and epileptic encephalopathy”). The focus of this review is on inherited syndromes. The phenotypes of genetic disorders affecting ion channels, metabolic signalling, membrane trafficking and exocytosis, cell adhesion, cell growth and proliferation are discussed. Red flags suggesting family of genes or even specific genes are highlighted. The knowledge of the phenotypical spectrum can indeed prompt the clinician to suspect specific etiologies, expediting the diagnosis.