Search Results (2,797)

Fragile X syndrome (FXS) is the most common form of X-linked intellectual disability (ID). This study aimed to share 30 years of experience in diagnosing FXS and determine its frequency in Thailand. We retrospectively reviewed 1480 unrelated patients (1390 males and 90 females) with ID, developmental delay, or autism spectrum disorder, or individuals referred for FXS DNA testing at Songklanagarind Hospital, Thailand, over a 30-year period. The samples were analyzed using cytogenetic methods, PCR-based techniques, and/or Southern blot analysis. Full mutations (>200 CGG repeats) were identified in 100 males (7.2%) and three females (3.3%). An intermediate allele was detected in one male, while no premutation was found in the index cases. Two males were suspected to have FMR1 gene deletions. Twelve families underwent prenatal testing during this study. Most families undergoing prenatal FXS diagnosis involved mothers who were premutation carriers and had given birth to children affected by FXS. This study represents the largest series of molecular genetic FXS testing cases reported in Thailand. The frequency of FXS identified in different cohorts of Thai patients across various periods was approximately 7%. This study enhances public awareness of at-risk populations and highlights the importance of prenatal testing and genetic counseling for vulnerable families. Full article

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are neurodevelopmental disorders with lifelong functional implications. Their potential role as emerging risk factors for cardiovascular diseases (CVDs) is increasingly acknowledged. The aim of this study was to conduct a comprehensive evaluation and meta-analysis of Mendelian Randomization (MR) studies exploring the causal effects of ADHD and ASD on various cardiovascular outcomes and vice versa. Three databases were searched, study quality was evaluated using a STROBE-MR checklist, and relevant data were extracted. In total, 14 studies revealed genetic associations between ADHD or ASD susceptibility and selected CVDs and vice versa. Notably, genetic markers for ADHD were linked to an increased risk of coronary artery disease, heart failure, and various types of stroke. Genetic predisposition to ASD raised the likelihood of atrial fibrillation and heart failure. Atrial fibrillation showed a causal relationship with elevated ADHD risk. Interestingly, hypertension was not associated with ADHD or ASD at the genetic level. Further efforts are needed to fully elucidate the basis of causal links from a mechanistic perspective. Overall, the results highlight the need for cardiovascular risk assessment and management in the clinical care of individuals with ADHD and ASD. Full article

Background/Objectives: Autism spectrum disorder (ASD) has been extensively studied through neuroimaging, primarily focusing on grey matter and more in children than in adults. Studies in children and adolescents fail to capture changes that may dampen with age, thus leaving only changes specific to ASD. While grey matter has been the primary focus, white matter (WM) may be more specific in identifying the particular biological signature of the neurodiversity of ASD. Diffusion tensor imaging (DTI) is the more appropriate tool to investigate WM in ASD. Despite being introduced in 1994, its application to ASD research began in 2001. Studies employing DTI identify altered fractional anisotropy (FA), mean diffusivity, and radial diffusivity (RD) in individuals with ASD compared to typically developing (TD) individuals. Methods: We systematically reviewed literature on 21 May 2025 on PubMed using the following strategy: (“autism spectrum”[ti] OR autistic[ti] OR ASD[ti] OR “high-functioning autism” OR Asperger*[ti] OR Rett*[ti]) AND (DTI[ti] OR “diffusion tensor”[ti] OR multimodal[ti] OR “white matter”[ti] OR tractograph*[ti]). Our search yielded 239 results, of which 26 were adult human studies and eligible. Results: Analysing the evidence, we obtained regionally diverse WM alterations in adult ASD, specifically in FA, MD, RD, axial diffusivity and kurtosis, neurite density, and orientation dispersion index, compared to TD individuals, mostly in frontal and interhemispheric tracts, association fibres, and subcortical projection pathways. These alterations were less prominent than those of children and adolescents, indicating that individuals with ASD may improve during brain maturation. Conclusions: Our findings suggest that white matter alterations in adults with ASD are regionally diverse but generally less pronounced than in younger populations. This may indicate a potential improvement or adaptation of brain structure during maturation. Further research is needed to clarify the neurobiological mechanisms underlying these changes and their implications for clinical outcomes. Full article

Background/Objectives: An important new consideration when studying autism spectrum disorder (ASD) is the bioenergetic mechanisms underlying the relatively recent rapid evolutionary expansion of the human brain, which pose fundamental risks for mitochondrial dysfunction and calcium signaling abnormalities and their potential role in ASD, as recently highlighted by insights from the BTBR mouse model of ASD. The rapid brain expansion taking place as Homo sapiens evolved, particularly in the parietal lobe, led to increased energy demands, making the brain vulnerable to such metabolic disruptions as are seen in ASD. Methods: Mitochondrial dysfunction in ASD is characterized by impaired oxidative phosphorylation, elevated lactate and alanine levels, carnitine deficiency, abnormal reactive oxygen species (ROS), and altered calcium homeostasis. These dysfunctions are primarily functional, rather than being due to mitochondrial DNA mutations. Calcium signaling plays a crucial role in neuronal ATP production, with disruptions in inositol 1,4,5-trisphosphate receptor (ITPR)-mediated endoplasmic reticulum (ER) calcium release being observed in ASD patient-derived cells. Results: This impaired signaling affects the ER–mitochondrial calcium axis, leading to mitochondrial energy deficiency, particularly in high-energy regions of the developing brain. The BTBR mouse model, with its unique Itpr3 gene mutation, exhibits core autism-like behaviors and metabolic syndromes, providing valuable insights into ASD pathophysiology. Conclusions: Various interventions have been tested in BTBR mice, as in ASD, but none have directly targeted the Itpr3 mutation or its calcium signaling pathway. This review presents current genetic, biochemical, and neurological findings in ASD and its model systems, highlighting the need for further research into metabolic resilience and calcium signaling as potential diagnostic and therapeutic targets for ASD. Full article

Background: Understanding the origin and natural organization of early infant vocalizations is important for predicting communication and language abilities in later years. The very frequent production of speech-like vocalizations (hereafter “protophones”), occurring largely independently of interaction, is part of this developmental process. Objectives: This study aims to investigate the gap durations (time intervals) between protophones, comparing typically developing (TD) infants and infants later diagnosed with autism spectrum disorder (ASD) in a naturalistic setting where endogenous protophones occur frequently. Additionally, we explore potential age-related variations and sex differences in gap durations. Methods: We analyzed ~1500 five min recording segments from longitudinal all-day home recordings of 147 infants (103 TD infants and 44 autistic infants) during their first year of life. The data included over 90,000 infant protophones. Human coding was employed to ensure maximally accurate timing data. This method included the human judgment of gap durations specified based on time-domain and spectrographic displays. Results and Conclusions: Short gap durations occurred between protophones produced by infants, with a mode between 301 and 400 ms, roughly the length of an infant syllable, across all diagnoses, sex, and age groups. However, we found significant differences in the gap duration distributions between ASD and TD groups when infant-directed speech (IDS) was relatively frequent, as well as across age groups and sexes. The Generalized Linear Modeling (GLM) results confirmed these findings and revealed longer gap durations associated with higher IDS, female sex, older age, and TD diagnosis. Age-related differences and sex differences were highly significant for both diagnosis groups. Full article

The present research examines the intersections of giftedness, disability status, and cultural identity through the case of Kent, a nine-year-old Asian American boy who is not only profoundly gifted but has also been diagnosed with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and possibly developmental coordination disorder (DCD). This study offers a comprehensive exploration of how these overlapping factors shape Kent’s early talent development and educational experiences, while also highlighting the challenges faced by his family and their need for a personalized, holistic support system tailored to his unique combination of abilities and disabilities. While Kent’s case is not generalizable, it underscores the critical importance of understanding the dynamic interplay among giftedness, disability status, and cultural identity in developing effective educational strategies. Furthermore, we advocate for personalized interventions that extend beyond conventional approaches, such as applied behavior analysis (ABA), to adequately address the complex needs of multi-exceptional individuals like Kent. Full article

Sensorimotor integration along the gastrointestinal (GI) tract is crucial for normal gut function yet remains poorly understood in the context of neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD). The genetic tractability of zebrafish allows investigators to generate molecularly defined models that provide a means of studying the functional circuits of digestion in vivo. Optical transparency during development allows for the use of optogenetics and calcium imaging to elucidate the mechanisms underlying GI-related symptoms associated with ASD. The array of commonly reported symptoms implicates altered sensorimotor integration at various points along the GI tract, from the pharynx to the anus. We will examine the reflex arcs that facilitate swallowing, nutrient-sensing, absorption, peristalsis, and evacuation. The high level of conservation of these processes across vertebrates also enables us to explore potential therapeutic avenues to mitigate GI distress in ASD and other NDDs. Full article

Background: Spectrin proteins are critical cytoskeleton components that maintain cellular structure and mediate intracellular transport. Pathogenic variants in SPTBN1, encoding βII-spectrin, have been associated with various neurodevelopmental disorders, including developmental delay, intellectual disability, autism spectrum disorder, and epilepsy. Here we report a Korean infant with infantile epileptic spasms syndrome (IESS) and an SPTBN1 mutation and provide a review of this mutation. Methods: The genomic data of the patient were analyzed by whole exome sequencing. A comprehensive literature review was conducted to identify and analyze all reported SPTBN1 variants, resulting in a dataset of 60 unique mutations associated with neurodevelopmental phenotypes. Case Presentation: A 10-month-old Korean female presented with IESS associated with a de novo heterozygous SPTBN1 mutation (c.785A>T; p.Asp262Val). The patient exhibited global developmental delay, microcephaly, hypotonia, spasticity, and MRI findings of diffuse cerebral atrophy and corpus callosum hypoplasia. Electroencephalography revealed hypsarrhythmia, confirming the diagnosis of IESS. Seizures persisted despite initial treatment with vigabatrin and steroids. Genetic analysis identified a likely pathogenic variant within the calponin homology 2 (CH2) domain of SPTBN1. Conclusions: This is the first report of an association between IESS and an SPTBN1 CH2 domain mutation in a Korean infant. This finding expands the clinical spectrum of SPTBN1-related disorders and suggests domain-specific effects may critically influence phenotypic severity. Further functional studies are warranted to elucidate the pathogenic mechanisms of domain-specific variants. Full article

Background/Objectives: Autism spectrum disorder (ASD) encompasses several neurodevelopmental disorders, whose onset is correlated to genetic and environmental factors. Although the etiopathogenesis is not entirely clear, the involvement of inflammatory processes, the endocannabinoid system, and alterations in the permeability and composition of the intestinal microbiota are known to occur. Methods: This review systematically explores the literature available to date on the most widely used murine models for the study of ASD, the main biomarkers investigated for the diagnosis of ASD, and the therapeutic potential of probiotics, with a particular focus on the use of strains of Lactiplantibacillus (Lpb.) plantarum in in vivo models and clinical trials for ASD. Results: Several studies have demonstrated that targeting multifactorial biomarkers in animal models and patients contributes to a more comprehensive understanding of the complex mechanisms underlying ASD. Moreover, accumulating evidence supports the beneficial effect of probiotics, including Lpb. plantarum, as a promising alternative therapeutic strategy, capable of modulating gut–brain axis communication. Conclusions: Probiotic supplementation, particularly with selected Lpb. plantarum strains, is emerging as a potential complementary approach for ameliorating ASD-related gastrointestinal and behavioral symptoms. However, further large-scale clinical studies are essential to validate their efficacy and determine optimal treatment protocols and dietary strategies. Full article

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

Objective: Retained primitive reflexes are associated with delayed motor and behavioral development in children with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). This study examined the effects of a 12-week structured exercise intervention on reflex integration, motor coordination, and socio-behavioral outcomes in these populations. Method: Fifteen children with ASD (13 boys, 2 girls) and twelve with ADHD (8 boys, 4 girls), aged 6–12 years, participated in rhythmic, balance, and coordination-based exercises. Primitive reflexes, including the asymmetrical tonic neck reflex (ATNR), were assessed using standardized protocols, and fine motor coordination was evaluated using the Finger and Thumb Opposition Test (FOT). Behavioral outcomes were measured using the Social Responsiveness Scale-2 (SRS-2) for the ASD group and the Conners 3 for the ADHD group. Results: The ASD group showed significant reductions in left-standing ATNR retention scores (p = 0.012) and improvements in right-hand FOT scores (p = 0.023). In the ADHD group, significant improvements were also observed in right-hand FOT scores (p = 0.007). Furthermore, Conners 3 Total and Global Index scores significantly decreased in the ADHD group (p = 0.016 and 0.020, respectively). Reflex retention patterns appeared broader and more bilateral in ASD than in ADHD, suggesting distinct motor developmental profiles. Conclusions: Short-term rhythmic, balance, and whole-body coordination exercise interventions may support behavioral and motor development in children with ASD and ADHD. Tailored programs emphasizing reflex integration hold promise for clinical and educational applications. Full article

Background: Very preterm infants are at increased risk of impairment. The objective was to explore the effect of immediate parent–infant skin-to-skin contact at very preterm birth on cognition, motor, social, and language development during the two first years. Methods: The Immediate Parent-Infant Skin-To-Skin Study (IPISTOSS) was a clinical trial with inclusions between April 2018 to June 2021, in three Scandinavian neonatal intensive care units. Infants were randomised at gestational age 28 + 0 to 32 + 6 weeks plus days, to immediate and continuous skin-to-skin contact at birth or conventional care, during the first six hours of life. Results: At three months, 42 infants underwent a General Movement Assessment. At four and 12 months, 69 and 62 infants, respectively, were assessed with the Alberta Motor Infant Scale. At 24 months, language and cognition were tested in 62 infants with the Bayley Scales of Infant and Toddler Development, third edition. Parents completed the Modified Checklist for Autism in Toddlers for 57 infants. There were no significant differences in motor development, cognition, or autism spectrum disorders. A significant difference in language scores in favour of immediate skin-to-skin contact, was found, when adjusted for fathers’ education, mothers’ education, and infants’ sex, Beta (95% CI): 32.00 (7.57, 56.43) p = 0.01, 11.51 (8.94, 55.06) p = 0.007, and 32.00 (7.85, 56.15) p = 0.01, respectively. Conclusions: Skin-to-skin contact immediately at birth did not enhance cognition, motor, or social development during the first two years of life but may have been important for language skills. Our findings support the World Health Organisation guidelines recommending iSSC for preterm born infants in all settings. Full article

Background: Autism spectrum disorder (ASD) is characterised by atypical behavioural and cognitive diversity, yet the neural underpinnings linking brain activity and individual presentations remain poorly understood. In this study, we investigated the relationship between resting-state functional magnetic resonance imaging (fMRI) signal complexity and intelligence (full-scale intelligence quotient (FIQ); verbal intelligence quotient (VIQ); and performance intelligence quotient (PIQ)) in male adults with ASD (n = 14) and matched neurotypical controls (n = 15). Methods: We used three complexity-based metrics: Hurst exponent (H), fuzzy approximate entropy (fApEn), and fuzzy sample entropy (fSampEn) to characterise resting-state fMRI signal dynamics, and correlated these measures with standardised intelligence scores. Results: Using a whole-brain measure, ASD participants showed significant negative correlations between PIQ and both fApEn and fSampEn, suggesting that increased neural irregularity may relate to reduced cognitive–perceptual performance in autistic individuals. No significant associations between entropy (fApEn and fSampEn) and PIQ were found in the control group. Group differences in brain–behaviour associations were confirmed through formal interaction testing using Fisher’s r-to-z transformation, which showed significantly stronger correlations in the ASD group. Complementary regression analyses with interaction terms further demonstrated that the entropy (fApEn and fSampEn) and PIQ relationship was significantly moderated by group, reinforcing evidence for autism-specific neural mechanisms underlying cognitive function. Conclusions: These findings provide insight into how cognitive functions in autism may not only reflect deficits but also an alternative neural strategy, suggesting that distinct temporal patterns may be associated with intelligence in ASD. These preliminary findings could inform clinical practice and influence health and social care policies, particularly in autism diagnosis and personalised support planning. 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