Epileptic encephalopathies of the Landau-Kleffner and continuous spike and waves during slow-wave sleep types: Genomic dissection makes the link with autism

摘要: Summary Purpose:  The continuous spike and waves during slow-wave sleep syndrome (CSWSS) the Landau-Kleffner (LKS) are two rare epileptic encephalopathies sharing common clinical features including seizures regression. Both CSWSS LKS can be associated with electroencephalography pattern of electrical status epilepticus part a continuum that at its benign end also includes rolandic epilepsy (RE) centrotemporal spikes. patients have behavioral manifestations overlap spectrum autism disorders (ASD). An impairment brain development and/or maturation complex interplay between genetic predisposition nongenetic factors has been suspected. A role for autoimmunity proposed but pathophysiology remains uncharacterized. Methods:  In recent years, participation genomic alterations in susceptibility to autistic demonstrated. involvement copy number variations (CNVs) 61 was questioned using comparative hybridization assays coupled validation by quantitative polymerase chain reaction (PCR). Key Findings:  Whereas showed highly heterogeneous architecture, several potentially pathogenic were detected. large these corresponded regions or genes (ATP13A4, CDH9, CDH13, CNTNAP2, CTNNA3, DIAPH3, GRIN2A, MDGA2, SHANK3) either ASD most them, involved speech language impairment, RE. Particularly, CNVs encoding cell adhesion proteins (cadherins, protocadherins, contactins, catenins) detected high frequency (≈20% patients) significant enrichment (cell adhesion: p = 0.027; molecule binding: p = 9.27 × 10−7). Significance:  Overall our data bring first insights into possible molecular LKS. overrepresentation strong genetic, networks, provide an exciting unifying view on links among CSWSS, LKS, ASD.