Search Results (632)

Background/Objectives: Autism spectrum disorders (ASDs) are neurodevelopmental conditions with early onset of clinical manifestations. ASD etiology is highly heterogeneous, with genetic factors being strong determinants of the behavioral problems and neurodevelopmental deficits. Fragile X syndrome (FXS) (OMIM #300624), caused by the transcriptional silencing of the FMR1 gene, represents the most common monogenic cause of autism. Our study included 226 boys with a diagnosis of ASD, for a systematic screening of genetic and epigenetic defects in the FMR1 gene promoter in a Romanian pediatric cohort. Methods: The methods, methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and triplet-primed PCR (TP-PCR)/melt curve analysis (MCA), were chosen for their ability to detect the methylation anomalies (the former) as well as repeat expansions in the FMR1 promoter (the latter). Results: Both methods used in our screening generated concordant results, detecting FMR1 full mutation in 4 out of 226 patients (~1.8%). This yield is similar to data obtained in larger studies. Three out of four boys presented the typical clinical features, in correlation with genetic findings. Conclusions: The combined use of MS-MLPA and TP-PCR/MCA-based assay was, in our experience, useful to fully describe the genetic defects responsible for FXS. A significant variability of clinical presentations was observed in our small group of children with FXS, from mild to severe intellectual disability and from atypical to characteristic dysmorphic features, as well as various behavioral problems. Full article

Background: Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental disorders characterized by a complex, multifactorial etiology with a strong genetic contribution. Our study aimed to evaluate the link between the burden of rare genetic variants within a specific panel of ASD and intellectual disability-associated genes and phenotypic variability in a cohort of children with autism in Slovakia. Methods: Gene burden scores were calculated based on pathogenic, likely pathogenic, and uncertain significance rare DNA variants identified by whole-exome sequencing. We then assessed the effect of three different scoring methods on the variance across 15 psycho-behavioral parameters describing the phenotypic profiles of 117 ASD probands. Results: The burden score showed a significant multivariate effect on the combination of psycho-behavioral parameters. This score was associated with the social affect of ADOS-2, as well as with the socialization domain, and total adaptive behavior scores from the Vineland Adaptive Behavior Scales-3 (VABS). While a score based solely on count of pathogenic and likely pathogenic variants did not show a multivariate effect, incorporating variants of uncertain significance revealed a multivariate effect on two adaptive behavior parameters: daily living skills and total adaptive behavior score (VABS). Conclusions: Our findings partially explain the variability in phenotypic manifestation in our ASD patient cohort, highlighting the importance of considering the cumulative effect of rare genetic variants, including those of uncertain significance, in shaping the diverse clinical presentation of ASD. Full article

Background and objectives: Neurosurgical intervention on the newborn’s developing brain is a risk factor for neurodevelopmental disorders (NDDs). These patients necessarily require regular, coordinated follow-up. The ventricular subgaleal shunt (VSGS) technique has been used since 2013 at Rouen University Hospital. Like any change in practice, this technique must be evaluated. In this paper, we describe the population of patients with hydrocephalus treated by VSGS, the complications associated with the procedure, and the outcome of these patients at two and six years old. Methods: This study was an observational, descriptive, retrospective, single-center study. Children included were those less than three months old with hydrocephalus treated by VSGS at Rouen University Hospital from January 2013 to December 2023. Data were anonymized and collected using EDSaN software. A descriptive analysis was performed. Results: Thirty-two patients were included in our study. Of these, 22 (69%) were born prematurely; 16 (50%) of these 22 had postnatal intraventricular hemorrhage (IVH) requiring treatment with VSGS. A total of three patients (13.6%) died within the first year of life; twenty-four patients (75%) required definitive shunting. Twenty-two patients were over 2 years old in our study. Only 10 of them acquired the ability to walk (45%). Cerebral palsy was present in 10 (45%) patients. Fifteen patients were over 6 years old; thirteen (87%) attended school, but six (40%) had special needs (the need of an assistant, or part-time schedule). In our study, only 24 patients (82%) were followed by a pediatrician trained in neurodevelopment at Rouen University Hospital, and 27 (93%) were followed by a neurosurgeon. Conclusions: This study describes all patients with hydrocephalus treated by VSGS at Rouen University Hospital between January 2013 and December 2023, as well as their complications and their neurological outcomes. The follow-up of these children at risk of NDDs is essential. Full article

Background and Objectives: Toe walking (TW) is frequently observed in children with Autism Spectrum Disorder (ASD), yet its clinical significance and association with comorbid conditions remain poorly understood. This study aimed to examine the prevalence of TW in a large Italian cohort of children with ASD and to explore its association with ASD severity, sleep disturbances, feeding behaviors, and gastrointestinal symptoms. Materials and Methods: A total of 289 children with ASD and 289 typically developing controls (TDC), matched for age and sex, were evaluated in a multicentric observational study. TW was assessed during neurodevelopmental evaluations. Sleep quality was assessed using the Sleep Disturbance Scale for Children (SDSC), feeding behaviors via the Brief Autism Mealtime Behavior Inventory (BAMBI), and gastrointestinal symptoms through clinical reporting. Statistical analyses included Chi-square tests, Mann–Whitney U tests, Spearman correlations, and logistic regressions. Results: TW was significantly more prevalent in the ASD group (27.3%) than in TDC (5.5%, p < 0.0001). Within the ASD group, TW occurred in 50.5% of children with Level 3 severity but was absent in Levels 1 and 2 (p < 0.0001). Males exhibited TW more frequently than females. Children with TW had higher SDSC scores (ρ = 0.33, p < 0.0001), though no subscale independently predicted TW. Constipation was reported in 100% of children with Level 3 ASD and was strongly correlated with SDSC total scores (ρ = 0.58, p < 0.0001). The Disorders of Arousal (DA) subscale emerged as an independent predictor of constipation (β = 0.184, p = 0.019). Conclusions: TW in ASD appears to be a marker of greater neurodevelopmental severity and is associated with sleep disturbances and gastrointestinal dysfunction. These findings support the hypothesis that TW may reflect broader dysfunctions involving the gut–brain axis, sensory processing, and motor control. The routine clinical assessment of TW should include the evaluation of sleep and somatic symptoms to better understand the multisystemic nature of ASD phenotypes. Full article

Background/Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental disorder distinguished by an extensive range of symptoms, including reduced social interaction, communication difficulties and tiresome behaviors. Early detection of ASD is important because it allows for timely intervention, which significantly improves developmental, behavioral, and communicative outcomes in children. However, traditional diagnostic procedures for identifying autism spectrum disorder (ASD) typically involve lengthy clinical examinations, which can be both time-consuming and costly. This research proposes leveraging automated machine learning (AUTOML) to streamline the diagnostic process and enhance its accuracy. Methods: In this study, by collecting data from various rehabilitation centers across Pakistan, we applied a specific AUTOML tool known as Tree-based Pipeline Optimization Tool (TPOT) for ASD detection. Notably, this study marks one of the initial explorations into utilizing AUTOML for ASD detection. The experimentations indicate that the TPOT provided the best pipeline for the dataset, which was verified using a manual machine learning method. Results: The study contributes to the field of ASD diagnosis by using AUTOML to determine the likelihood of ASD in children at prompt stages of evolution. The study also provides an evaluation of precision, recall, and F1-score metrics to confirm the correctness of the diagnosis. The propose TPOT-based AUTOML framework attained an overall accuracy 78%, with a precision of 83%, a recall of 90%, and an F1-score of 86% for the autistic class. Conclusions: In summary, this research offers an encouraging approach to improve the detection of autism spectrum disorders (ASD) in children, which could lead to better results for affected individuals and their families. Full article

Background/Objectives: Atypical sensory processing is increasingly recognized as a transdiagnostic dimension of neurodevelopmental disorders (NDDs), with critical implications for emotional and behavioral regulation. This study aimed to identify distinct sensory profiles in preschool children with NDDs and to examine their associations with emotional–behavioral and cognitive/developmental functioning. Methods: A total of 263 children (aged 21–71 months) diagnosed with autism spectrum disorder (ASD), language disorder (LD), or other NDDs (ONDD) were recruited. Sensory processing was assessed using the SPM-P, emotional–behavioral functioning was assessed via the CBCL 1½–5, and cognitive/developmental levels were assessed through standardized instruments. Latent profile analysis (LPA) was conducted to identify sensory subtypes. Group comparisons and multinomial logistic regression were used to examine profile characteristics and predictors of profile membership. Results: Three sensory profiles emerged: (1) Multisystemic Sensory Dysfunction (20.1%), characterized by pervasive sensory and emotional difficulties, primarily observed in ASD; (2) Typical Sensory Processing (44.9%), showing normative sensory and emotional functioning, predominantly LD; and (3) Mixed Subclinical Sensory Processing (35%), with subclinical-range scores across multiple sensory and emotional domains, spanning all diagnoses. Higher cognitive functioning and fewer internalizing symptoms significantly predicted membership in the typical profile. A gradient of symptom severity was observed across profiles, with the Multisystemic group showing the most pronounced emotional–behavioral impairments. Conclusions: Distinct sensory–emotional phenotypes were identified across diagnostic categories, supporting a dimensional model of neurodevelopment. Sensory profiles were strongly associated with emotional functioning, independently of diagnostic status. Early sensory assessment may therefore offer clinically meaningful insights into emotional vulnerability and inform targeted interventions in preschool populations with NDDs. Full article

Approximately 18% of U.S. children experience cognitive and behavioral challenges, with both genetic and environmental contributors. We examined if household insecticides, particularly those used in and around the home and on pets, are associated with neurodevelopmental changes. Data were from children aged 24–60 months in the CHARGE study with the following classifications: autism spectrum disorder (ASD, n = 810), developmental delay (DD, n = 192), and typical development (TD, n = 531). Exposure to indoor, outdoor, and pet insecticides was reported for the period from three months pre-conception to the second birthday. Cognitive and adaptive functioning were assessed using the Mullen Scales of Early Learning and Vineland Adaptive Behavior Scales. Linear regression was used to evaluate associations by diagnostic group, adjusting for confounders. Flea/tick soaps, shampoos, and powders used during year two were significantly associated with lower cognitive and adaptive scores in children with ASD after FDR correction. Flea/tick skin treatments in early pregnancy were associated with reduced scores in the DD group, though not significant after correction, especially when used with high frequency. No associations were observed in TD children. These findings underscore the need to examine early-life exposure to non-agricultural insecticides as modifiable risk factors for neurodevelopment. Full article

Background/Objectives: Neurofibromatosis type 1 (NF1) and Noonan syndrome spectrum disorders (NSSD) are the most common RASopathies, resulting from germline mutations that affect the RAS-MAPK signaling pathway. Both are associated with increased risk for neurodevelopmental and psychiatric conditions, yet few studies have used structured diagnostic interviews to compare their psychiatric comorbidities. Methods: We conducted clinician-administered DSM-5 diagnostic assessments (KSADS) in 123 children with RASopathies (NF1 = 29, NSSD = 94; ages 5–15). Diagnosis prevalence was compared within each group and to population-based estimates. Results: Psychiatric diagnoses were highly prevalent, at 79.3% in NF1 and 76.6% in NSSD, with ADHD (NF1 = 72.4%, NSSD = 51.1%) and anxiety disorders (NF1 = 37.9% and NSSD = 43.6%) being the most common, rates substantially higher than those reported in general population estimates. Behavioral and sleep disorders were identified in approximately 25% of both groups. Notably, social anxiety disorder was identified in 14.9% of NSSD but not in NF1. Full-scale IQ did not significantly differ by diagnosis status. Specific anxiety disorders, elimination disorders, obsessive–compulsive disorder, and post-traumatic stress disorder were characterized, expanding the known psychiatric phenotype of RASopathies. Conclusions: Children with NF1 and NSSD demonstrate similarly high rates of ADHD, anxiety, and behavioral disorders compared to the general population; in addition, we report sleep disorders in NSSD and characterize psychiatric disorders not previously described in RASopathies. The shared psychiatric profiles may reflect the common effect of RAS-MAPK pathway dysregulation on psychiatric outcomes. These findings highlight the need for early, syndrome-informed mental health screening and intervention in the clinical care of individuals with RASopathies. Full article

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is a complex neurodevelopmental condition typically requiring information from multiple informants for accurate diagnosis. However, the consistency and diagnostic value of reports from teachers, parents, primary care providers (PCPs), and other professionals remain debated. This study aimed to examine the role and diagnostic accuracy of different informants in the referral and diagnostic process for ADHD in children aged 3–11. Methods: This retrospective study analyzed data from 120 children referred for suspected ADHD. Initial reports were obtained from teachers, parents, PCPs, and other professionals, and final diagnoses were determined through comprehensive neuropsychiatric evaluations. Diagnostic concordance and informant-specific contributions were assessed. Results: Of the 120 children, 64 (53.3%) received an ADHD diagnosis. Teachers were the most frequent informants, followed by parents, with fewer referrals from PCPs and other professionals. No significant differences in diagnostic accuracy were found among informants, aligning with previous studies suggesting that no single informant is superior in identifying ADHD. Notably, over 93% of referred children were diagnosed with a neuropsychiatric disorder, though not necessarily ADHD. Conclusions: The findings underscore the importance of combining reports from parents and teachers to capture symptom expression across different environments, which is essential for accurate ADHD diagnosis. Enhanced training for informants and a multidisciplinary approach is recommended to improve diagnostic accuracy and support early identification and intervention efforts. These results support nuanced evaluation strategies that account for informant variability and help mitigate potential misinterpretations of ADHD symptoms. Full article

Neuro-Affective Intelligence (NAI) integrates neuroscience, psychology, and artificial intelligence to support neurodivergent children through personalized Child–Machine Interaction (CMI). This paper presents an adaptive neuro-affective system designed to enhance engagement in children with neurodevelopmental disorders through serious games. The proposed framework incorporates real-time biophysical signals—including EEG-based concentration, facial expressions, and in-game performance—to compute a personalized engagement score. We introduce a novel mechanism, Bayesian Immediate Feedback Learning (BIFL), which dynamically selects visual, auditory, or textual stimuli based on real-time neuro-affective feedback. A multimodal CNN-based classifier detects mental states, while a probabilistic ensemble merges affective state classifications derived from facial expressions. A multimodal weighted engagement function continuously updates stimulus–response expectations. The system adapts in real time by selecting the most appropriate cue to support the child’s cognitive and emotional state. Experimental validation with 40 children (ages 6–10) diagnosed with Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) demonstrates the system’s effectiveness in sustaining attention, improving emotional regulation, and increasing overall game engagement. The proposed framework—combining neuro-affective state recognition, multimodal engagement scoring, and BIFL—significantly improved cognitive and emotional outcomes: concentration increased by 22.4%, emotional engagement by 24.8%, and game performance by 32.1%. Statistical analysis confirmed the significance of these improvements ($p<0.001$, Cohen’s $d>1.4$). These findings demonstrate the feasibility and impact of probabilistic, multimodal, and neuro-adaptive AI systems in therapeutic and educational applications. Full article

While genetic mechanisms in neurodevelopmental disorders are well studied, the mechanisms of environmental factors such as prenatal stress are less understood. Our lab previously characterized miRNA changes associated with stress during pregnancy in mouse brains and in maternal blood from mothers of children with ASD and indicated that prenatal stress can be linked to epigenetic markers. These miRNAs could be used as discovery biomarkers for stress exposure, as well as predictors of neurodevelopmental outcomes. In this pilot study, we gathered saliva samples and stress survey questionnaires from 83 pregnant African American women (ages 18–40) at the time of their ultrasound performed at 20 weeks. miRNA analysis was performed on the 10 highest- and 10 lowest-stress subjects. Out of 6631 miRNAs examined, 34 had significant differential expression, with 5 being upregulated and 29 downregulated in the high-stress group. Predicted targets of differentially expressed miRNAs revealed significant enrichment in neurodevelopmental pathways, including forebrain development, sensory system development, and neuronal growth regulation. This may suggest the potential developmental salience of these miRNA profiles. Future research will examine the neurodevelopmental outcomes of these pregnancies to determine the predictive potential of these miRNAs. This may help identify individuals at greatest risk after stress exposure during pregnancy. Full article

Objectives: Sleep serves a crucial role in the optimal development of cognitive, emotional, and physical domains. Sleep disturbances and disorders have been reported to frequently occur in many neurodevelopmental conditions, including ADHD and Autism Spectrum Disorder. The connection between dyslexia and sleep, however, is sparsely explored. This community study aimed to enhance knowledge about sleep disturbances in children with dyslexia and explore the potential impact of anxiety. Method: The parents of 160 children aged 7–13 years old with a primary diagnosis of dyslexia completed the Children’s Sleep Habits Questionnaire (CSHQ) and the Spence Children’s Anxiety Scale (SCAS). Results: Sixty-six percent of the children showed pathological levels of sleep disturbances, with clinical scores observed in the subscales of Sleep Onset Delay, Sleep Anxiety, and Daytime Sleepiness. Overall, sleep and anxiety were correlated, but anxiety levels were not elevated and not correlated with Sleep Onset Delay. Conclusions: The current results suggest that the majority of children with dyslexia suffer from sleep disturbances, such as delayed sleep onset and shorter sleep durations, irrespective of the scores given on the anxiety scale. Given the importance of sleep for optimal development, there is an alarming need for more studies to be carried out to explore additional factors that interact with healthy sleep to develop sleep interventions. Full article

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder marked by neurological regression, autonomic dysfunction, seizures, and significant sleep and breathing abnormalities. About 80% of affected individuals, especially young children, experience sleep disturbances such as insomnia, sleep-disordered breathing, nocturnal vocalizations, bruxism, and seizures. Breathing irregularities during sleep—like apnea, alternating hyperventilation, and hypoventilation—are common, with both obstructive and central sleep apnea identified through polysomnography. This review focuses on the prevalent sleep disorders in children with Rett syndrome and highlights current recommendations for the management of sleep disorders. Full article

Background/Objectives: Cerebral palsy (CP) is a neurodevelopmental disorder associated with sleep disturbances, particularly sleep-disordered breathing (SDB), and is often linked to an increased risk of obstructive sleep apnea (OSA). OSA is underdiagnosed in this population due to the lack of standardized methods and limited access to appropriate diagnostic technologies and appropriate equipment. Thus, this study aimed to investigate the presence and severity of sleep disorders, with a particular focus on OSA, in children and adolescents with CP compared to their typically developing peers. Methods: This observational, clinical, and prospective study included 28 children and adolescents with CP and 32 age- and sex-matched typically developing individuals. Sleep disturbances were assessed using the Sleep Disturbance Scale for Children (SDSC) and a high-resolution oximeter plus actigraphy combined with a cloud-based algorithm for the detection of obstructive sleep apnea (Biologix^® system), which provided data on oxygen saturation, snoring, movement during sleep, and total sleep time. Results: According to the SDSC, 92% of children and adolescents with CP presented scores indicative of sleep disturbances, compared to 31% of typically developing individuals. SDB was the most prevalent subtype (64%) and overnight oximetry revealed that 100% of the CP group presented oxygen desaturation index (ODI) values consistent with a diagnosis of OSA. The CP group also exhibited significantly lower mean SpO₂, longer snoring duration, shorter total sleep time, and prolonged sleep latency compared to the typically developing group. Conclusions: Children and adolescents with cerebral palsy (CP) exhibit a high prevalence of sleep disturbances, with increasing evidence indicating a significant occurrence of sleep-disordered breathing (SDB), particularly obstructive sleep apnea (OSA). Full article

Background: Developmental delay and intellectual disability (DD/ID) are frequently accompanied by epilepsy, and growing evidence implicates variants in voltage-gated calcium channel genes in their pathogenesis. This study aimed to investigate the association of polymorphisms in CACNA1A, CACNA1C, and CACNA1H with DD/ID and epilepsy comorbidity in Korean children. Methods: We retrospectively analyzed 141 pediatric patients diagnosed with DD/ID who underwent whole-exome sequencing (WES) and were not found to have pathogenic monogenic variants. Nine single-nucleotide polymorphisms (SNPs) across CACNA1A, CACNA1C, and CACNA1H were selected based on functional annotation scores and prior literature. Genotype data were extracted from WES variant files, and allele and genotype frequencies were compared with control data from the gnomAD East Asian population and the Korean Reference Genome Database (KRGDB). Subgroup analyses were performed according to epilepsy comorbidity. Results: The CACNA1A rs16023 variant showed a significantly higher B allele frequency in DD/ID patients than in both control datasets and was also associated with epilepsy comorbidity. Genotype distribution analysis revealed that the BB genotype of rs16023 was more frequent in patients with epilepsy. Conclusions: The CACNA1A rs16023 variant may contribute to genetic susceptibility to DD/ID and epilepsy in Korean children, potentially through regulatory mechanisms. These findings support the relevance of calcium channel genes in neurodevelopmental disorders and highlight the importance of integrating functional annotation in variant prioritization. Full article