0041 Neuronal circuits convergently disrupted in the genetic basis of sleep phenotypes and rare neurodevelopmental syndromes

Abstract Introduction Sleep-related phenotypes have been frequently reported in early on-set epileptic encephalopathies (EE) and developmental delay (DD) syndromes, particular syndromes related to autism spectrum disorder (ASD). Yet the convergent pathogenetic mechanisms between these comorbidities are largely unknown. Methods We first performed a gene enrichment study that identified shared risk genes among rare EE/neurodevelopmental disorders (NDD), DD genetic sleep disturbances. then determined cellular molecular pathways enriched those two onset mental illnesses, aiming identify disparities commonalities phenotypic groups. Results The set was observed as significantly overlapped with lists associated (i.e. EE/NDD sets), suggesting contribution. Similarities across intersect comprehended mostly synapse-related pathways, such retrograde endocannabinoid signaling, serotonergic GABAergic synapse. Network analysis indicates vs specific clusters synaptic transcriptional regulation, respectively. Longstanding functional patterns previously described EE NDD architecture were recaptured after dissecting overlap disturbances, during neurodevelopment different alterations on circadian rhythm. Conclusion overlapping biological highlighted by this may serve primer for new investigations of disturbances or without epilepsy. Support (if any) Our studies supported Associação Fundo de Incentivo à Pesquisa (AFIP). S.T. M.L.A. received CNPq fellowships.