Dup15Q Syndrome

Autism spectrum disorder (ASD) , hereafter referred to as autism, is a group of neurodevelopmental disorders caused by genetic and environmental factors. Its core symptoms are social impairment, repetitive stereotyped behaviors, and restricted interests. The 15q11-13 region of the human chromosome is a locus prone to structural abnormalities leading to neurological disorders. Maternal duplications within this region lead to Dup15q syndrome , which accounts for approximately 1% of ASD cases . This region harbors multiple alleles, and current research indicates that the pathophysiological alterations in this syndrome primarily involve UBE3A . Among all genes in the 15q11-13 region, only UBE3A exhibits cell-type-specific maternal monoallelic expression . Consequently, duplication of the UBE3A gene is considered the primary pathogenic factor in the pathology of Dup15q syndrome. Studies show that the metabolic conversion of retinol to retinoic acid is impaired in ASD patients with UBE3A overexpression and corresponding animal models . Notably, dietary supplementation with all-trans retinoic acid (ATRA) has been shown to significantly ameliorate autism-like behaviors caused by UBE3A overexpression in male mice . This study aims to evaluate ATRA treatment in children with Dup15q syndrome-related autism , assessing changes in their ADOS-2 scores , to potentially provide a novel therapeutic approach for autism treatment.

Recent studies have shown that the aperiodic part of the signal (neuronal avalanches) of electroencephalography (EEG) contains important information about the dynamics of neuronal networks. Indeed, this has helped to identify functionally altered areas in patients with temporal epilepsy by simply using the resting EEG signal. Furthermore, it has been seen that the propagation of neuronal avalanches (VNs) correlates with the morphological organization of the cerebral cortex. Therefore, NAs represent a measure with direct utility for studying functional reorganization pre and post drug/surgical treatment. In addition, the aperiodic portion of the signal may represent a noninvasive measure of the excitation/inhibition relationship, which is known of being altered both in epilepsy and in some rare neurodevelopmental syndromes (example: Angelman and Dup15q)