ABSTRACT Syndromic autism refers to autism spectrum disorder (ASD) occurring as part of an identifiable genetic syndrome. Helsmoortel–Van der Aa syndrome (HVDAS/ADNP syndrome) is a rare autosomal dominant neurodevelopmental disorder caused by heterozygous pathogenic variants in the ADNP gene. We report a 10‐year‐old boy with ASD and intellectual disability who exhibited delayed motor and language development, characteristic facial dysmorphism, early tooth eruption, endocrine abnormalities, electroencephalography (EEG) abnormalities, and urogenital findings. Following unremarkable karyotyping and chromosomal microarray analysis (CMA), whole‐exome sequencing identified a heterozygous pathogenic de novo frameshift variant, c.1239_1240del, p .(Gln414Valfs*25) in ADNP . This case emphasizes the importance of considering a syndromic etiology in children with ASD accompanied by developmental delay, dysmorphic features, neurological findings, or multisystem involvement, and supports comprehensive genetic evaluation when first‐tier testing is unrevealing.
The pathophysiology of attention-deficit/hyperactivity disorder (ADHD) is not fully understood, but increasing evidence suggests that gut microbiota may play a role. This study compared the gut microbiota of children with ADHD with that of a control group of healthy children, and examined their dietary and sleep habits. Ten medication-naïve children aged 612 years who had recently been diagnosed with ADHD and ten healthy controls were included. ADHD diagnoses were confirmed using the Schedule for Affective Disorders and Schizophrenia for School-Age ChildrenPresent and Lifetime Version (K-SADS-PL). Sleep and eating habits were assessed using the 2nd Level Sleep Disorder Short Form, the Children's Eating Behaviour Inventory, and a form to collect sociodemographic and clinical information. The gut microbiota were analysed using 16S NGS metagenome analysis. A significant decrease in the Shannon and Simpson diversity index values was observed in the ADHD group compared to the control group. Despite the presence of a percentage difference, no statistically significant differences were observed between the groups with respect to species, genus, family, order, class or phylum. Following evaluation of the sleep and eating habit scale scores, no statistically significant difference between the groups was determined.These findings suggests that children with ADHD may alter gut microbiota diversity.However, the absence of significant taxonomic differences and the small sample size mean that these results should be interpreted with caution. Further, larger, adequately powered studies are needed to validate these findings and clarify the potential role of gut microbiota in the pathophysiology of ADHD.
The integrity of the brain's barrier systems-the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB)-is crucial for central nervous system homeostasis. Oxytocin (OXT), a neuropeptide with emerging peripheral roles, has been implicated in vascular function. This study investigates the hypothesis that OXT directly modulates the functional properties of the BBB and BCSFB via receptor-mediated mechanisms. Using Transwell monoculture in vitro models employing primary rat brain microvascular endothelial cells (BMECs) and choroid plexus epithelial cells (ChPlECs), we first confirmed biological purity and demonstrated constitutive expression of both OXT receptor (OXTR) and the receptor for advanced glycation end products (RAGE) in both cell types. Notably, OXTR and RAGE expression were significantly higher in choroid plexus cells compared to BMECs. Treatment with 800 nM OXT significantly increased transendothelial/epithelial electrical resistance (TEER) in both models, indicating enhanced barrier tightness, with a more rapid effect observed in the BCSFB model. However, paracellular permeability to Lucifer yellow remained unchanged. OXT treatment induced a transient increase in lactoperoxidase (LPO) levels in the conditioned medium at 24 h, followed by a decline at 48-72 h, coinciding with peak TEER values. These findings establish OXT as a potent modulator of cerebral barrier function, with the BCSFB exhibiting higher sensitivity. This novel role of OXT in barrier regulation extends its physiological repertoire and presents a potential therapeutic avenue for neurodevelopmental and neurodegenerative disorders associated with barrier dysfunction.
Neurotoxicity induced by the repeated anesthetic exposure during the neurodevelopmental period and its potential long-term cognitive consequences remain a matter of concern. This study investigated the neurobiological and histological changes in the hippocampus as well as potential long-term neurobehavioral alterations, following repeated administration of ketamine (KET) and dexmedetomidine (DEX) in neonatal rats. Postnatal Day 7 (PND7) rat pups were randomly assigned to four groups: Control (0.9% NaCl), KET (50 mg/kg), DEX (25 µg/kg), and DEXKET (DEX (25 µg/kg) + KET (50 mg/kg)). Intraperitoneal (i.p.) injections were performed for three consecutive days (PND8-10). Developmental neurotoxicity was assessed by measuring apoptotic markers (caspase-3, Bax, and Bcl-2) and pyroptosis-related proteins (caspase-1, gasdermin D, IL-1β, and IL-18) in hippocampus via ELISA. Western blotting was used to analyze long-term hippocampal caspase-1, brain-derived neurotrophic factor (BDNF), and growth associated protein 43 (GAP43) levels. Long-term cognitive effects, including learning, memory, and attention, were evaluated on PND40 using the Barnes maze and the novel object recognition (NOR) tests. Hippocampal morphology was examined by Nissl staining. Although KET or DEX alone did not alter classical apoptotic pathways, they significantly reduced caspase-1. However, both KET and DEX alone impaired recognition memory and attention in the long term, without altering spatial learning. Notably, the combined administration of KET and DEX enhanced sedation while maintaining caspase-1, BDNF, and GAP43 levels close to control values, preserving recognition memory and spatial learning. These findings indicate that co-administration of KET and DEX during the neonatal period may provide a safer anesthetic strategy by reducing cognitive side effects and modulating neuroinflammatory pathways.
Smith-Magenis syndrome (SMS) is a rare multisystem genetic disorder caused by a 17p11.2 microdeletion or pathogenic variants in the retinoic acid-induced 1 (RAI1) gene. It is characterized by developmental delay, distinctive craniofacial features, behavioral dysregulation, and inverted sleep-wake rhythm. Because early clinical findings are often nonspecific, diagnosis is frequently delayed, and patients may initially present to child psychiatry services with behavioral complaints. We report a 5-year-old girl referred for hyperactivity, severe circadian sleep disturbance with recurrent nocturnal awakenings, self-injurious behaviors, sensory-seeking behaviors, and developmental delay. Comprehensive psychiatric, developmental, neurological, physical, and genetic evaluations revealed a 17p11.2 microdeletion involving both RAI1 and folliculin (FLCN). The diagnosis of SMS was confirmed, and the involvement of FLCN indicated additional potential long-term medical risks. This case underscores the importance of considering genetic etiologies in children presenting with severe behavioral dysregulation and sleep problems and highlights the critical role of comprehensive genetic assessment in guiding diagnosis, management, and long-term follow-up.
