Search Results (567)

Background: Kleefstra syndrome (KS) is a rare neurodevelopmental disorder caused by haploinsufficiency of EHMT1; it is characterized by global developmental delay, intellectual disability, hypotonia, distinctive facial features, and variable congenital anomalies. Autistic features, behavioral abnormalities and severe speech impairment are frequently reported. However, molecularly confirmed cases of KS from Africa remain extremely limited, largely due to restricted access to genomic diagnostic infrastructures. Methods: We describe a 15-month-old patient from Rwanda presenting with neonatal hypotonia, global developmental delay, short stature, and characteristic dysmorphic facial features. Comprehensive clinical evaluation was performed, followed by trio-based exome sequencing to identify the underlying genetic cause of this neurodevelopmental disorder. Results: Exome sequencing identified a de novo heterozygous frameshift variant in EHMT1 (NM_024757.5: c.2871dup; p. Phe958Leufs*219), confirming the diagnosis of KS. Conclusions: This report presents the first molecularly confirmed case of KS in Rwanda. It highlights additional clinical features like bilateral 5th toe clinodactyly, short stature and absence of obesity in KS. There is a need to further delineate the study of EHMT1 and investigate the natural history of KS across different populations for optimal patient management and to reduce diagnostic odyssey. The diagnostic utility of exome sequencing for neurodevelopmental disorders needs to be strengthened, with strong emphasis on expanding genomic medicine to help diagnose rare diseases in resource-limited settings. Full article

Background/Objectives: Comparative sociogenomics combines multiple scientific fields to investigate the genetic basis of social behavior across species. Our aim was to uncover the genetic roots of human sociability with possible implications for autism, a neurodevelopmental disorder characterized by social and communication deficits. Methods: We conducted molecular network analysis on 659 sociability-related genes from different animal species, including humans. Results: We identified a network of 240 genes strongly associated with autism (p < 10⁻¹⁵), with 194 inferred. These genes were grouped into 23 functional communities related to cell–cell junctions and communication, inflammatory and synaptic signaling, neurotransmitter receptors and semaphorin signaling among the more enriched meta-pathways. Some network genes were clustered in nine chromosomal bands (FDR < 0.25), indicating genes’ functional cooperation, shared evolutionary history, and coordinated regulation, and few genes are physically in linkage with ASD genes (within 0.5 cM) or controlled by human-accelerated regions. Conclusions: The most compelling inferred autism risk genes are MED12, FZD9, and DMD since they are differentially expressed in autistic brains, physically linked to key autism genes, controlled by human-accelerated regions, or mapped to chromosomal regions enriched in network genes. If validated, they could represent novel biomarkers, advancing the understanding of autism’s genetic makeup. Full article

Objectives: Autism Spectrum Disorder (ASD) and psychotic disorders have long been considered separate diagnostic entities, yet increasing evidence highlights shared neurodevelopmental mechanisms and symptom overlap. Psychotic-like experiences have been frequently reported in individuals with ASD, while subthreshold autistic traits (ATs) in first-degree relatives may also confer vulnerability to psychotic symptoms. This cross-sectional study aimed to compare psychotic spectrum manifestations among adults with ASD, their first-degree relatives (BAP), and controls (HCs), to explore associations between psychotic and ATs, and to evaluate whether psychotic symptoms predict diagnostic group membership. Methods: 22 adults with ASD, 22 BAP, and 24 HCs were evaluated with the Psychotic Spectrum–Self Report (PSY-SR) and the Adult Autism Subthreshold Spectrum (AdAS Spectrum). Results: ASD participants scored significantly higher on the PSY-SR. BAP individuals showed higher PSY-SR total scores compared to HCs, though less severe than in ASD. All PSY-SR domains positively correlated with all AdAS Spectrum domains, with few exceptions. Multinomial regressions showed that higher PSY-SR total scores significantly predicted ASD and BAP membership, and that the PSY-SR Paranoid domain score specifically predicted inclusion in both groups in relation to HCs. Conclusions: Psychotic spectrum symptoms are elevated not only in individuals with ASD but also among first-degree relatives, supporting a continuum linking autistic and psychotic vulnerabilities. The strong association between paranoid symptoms and ATs highlights a dimension of potential clinical relevance for early identification and assessment. These findings reinforce shared neurodevelopmental pathways between the autism and psychosis spectra and underscore the importance of dimensional approaches across diagnostic categories. Full article

Autism Spectrum Disorder (ASD) is a developmental disorder that manifests a broad variability of phenotypes. The underlying factors contributing to the diverse presentation of autistic phenotypes remain poorly understood. Studies have shown that environmental and genetic factors could contribute to ASD. Additionally, there is a sex bias in the disorder, where the prevalence in males is higher than in females. But it is still unknown how exposure to similar risk factors can lead to different phenotypes. The three-hit theory states that the vulnerability of an individual to develop ASD is modulated by the interplay between genetic predisposition, sex, and environmental insults. To better understand this phenomenon, we investigated whether an environmental insult, via maternal immune activation (MIA) during pregnancy could influence the development of the autistic-like phenotype in a genetically predisposed mouse strain, contactin-associated protein-like 2 (CNTNAP2) knockout. CNTNAP2 knockout, sex, and maternal immune activation had significantly additive effects on repetitive/stereotyped and social behavior in the offspring, while working memory and sensory gating were not affected by hits. These results indicate that genetics, sex, and environment interact to influence autistic-like phenotypes in a behavior-specific manner. Full article

Background: Eating disorders (EDs) frequently co-occur with trauma-related symptoms and elevated autistic traits (ATs), both of which contribute to clinical complexity. Social camouflaging, strategies used to mask or compensate for ATs, has been increasingly described in ED populations, yet its relationship with trauma-related symptoms remains poorly understood. This study aimed to examine the association between social camouflaging and post-traumatic stress symptoms in individuals with EDs and to evaluate whether trauma-related symptomatology is associated with camouflaging behaviors. Methods: A total of 67 ED patients were assessed using the Adult Autism Subthreshold Spectrum, the Trauma and Loss Spectrum—Self Report (TALS-SR), the Camouflaging Autistic Traits questionnaire (CAT-Q), and the Eating Disorder Inventory (EDI-2). Participants were divided into high-trauma-symptoms (HTS) (N = 36, 53.7%) and low-trauma-symptoms (LTS) (N = 31; 46.3%) groups based on TALS-SR criteria. Results: The sample was predominantly female (92.5%), and gender distribution differed between groups, which may represent a potential confounding factor and limits the generalizability of the findings. The HTS group reported significantly higher TALS-SR, EDI-2, CAT-Q, and AdAS Spectrum scores, although for the latter the p-value was barely significant (p = 0.046). No differences emerged in the distribution of ED diagnoses between groups. CAT-Q scores were significantly positively correlated with TALS-SR total scores and with domains related to reaction to losses, maladaptive coping, avoidance/numbing, and personal vulnerability. Regression analyses showed that overall trauma-related symptoms were significantly associated with greater camouflaging; however, the proportion of explained variance was modest, suggesting that trauma-related symptoms represent only one of multiple factors linked to camouflaging. Conclusions: Among individuals with EDs, higher trauma-related symptomatology is linked to greater use of social camouflaging strategies. These findings suggest that camouflaging may represent a transdiagnostic correlate connecting neurodevelopmental vulnerability and trauma responses within ED populations, underscoring the importance of integrated assessment and trauma-informed care. Full article

Sex education for students with autism spectrum disorder in Saudi Arabia remains limited and underdeveloped, raising concerns related to safety, body awareness, and healthy personal development during the school years. This qualitative study employed semi-structured interviews with four teachers and three family members and was analyzed using thematic analysis. Participants discussed school-aged autistic children educated in mainstream inclusive settings alongside peers with diverse learning profiles. All students referenced were verbally communicative, and some were reported to have co-occurring developmental or behavioral conditions. The findings revealed key challenges, including heightened vulnerability to harassment, limited understanding of bodily boundaries, and difficulties related to personal hygiene and privacy. Participants also identified substantial gaps in existing curricula, inconsistent teacher preparation, and limited access to guidance for families, resulting in fragmented approaches to sex education. The findings highlight the urgent need for culturally responsive, developmentally appropriate sex education curricula, targeted professional development for teachers and families, and strengthened collaboration between home and school. Such efforts are essential to promote safety, well-being, and protection for autistic students within the Saudi educational context. Full article

Background: Adolescents with neurodevelopmental disorders (NDDs), particularly autism spectrum disorder (ASD) and borderline intellectual functioning/intellectual disability (BIF/ID), represent a clinically complex population in psychiatric emergency settings, with unclear contributions to acute psychopathology and suicide risk. Aims: This study examined whether ASD and BIF/ID differentially influence clinical severity, psychopathological profiles, and suicidality in adolescents admitted for psychiatric emergencies, comparing high-functioning ASD, ASD with cognitive impairment, and adolescents without NDDs. Methods: We conducted a retrospective, single-center cohort study including 206 consecutive patients aged 11–17 years admitted to a psychiatric emergency unit between January 2022 and December 2023. Patients were stratified into four groups: ASD (ASD-HF; ASD-BIF/ID), BIF/ID and N-ASD/N-BIF/IDClinical severity, global functioning, psychiatric diagnoses, adverse childhood experiences, emotional dysregulation, and suicidality were assessed using standardized diagnostic and behavioral measures. Group comparisons were performed to identify predictors of suicidality. Results: ASD-BIF/ID patients exhibited the lowest global functioning, whereas ASD-HF adolescents showed functioning comparable to controls. Suicidal ideation and behaviors were significantly more frequent in ASD-HF. BIF/ID was associated with greater behavioral impairment and lower suicidality. Conclusions: ASD and BIF/ID may differentially shape psychiatric emergency presentations. Adolescents with high-functioning ASD showed a higher prevalence of suicidality in this specific clinical context. Limits: This study is limited by its cross-sectional, single-center, and retrospective design, small and uneven subgroup sizes, and assessment tools not specifically validated for autistic or intellectually disabled populations. The high prevalence of bipolar spectrum disorders may reflect referral bias. Despite these limitations, adolescents with high-functioning ASD exhibited elevated suicidality, underscoring the importance of risk assessment adapted to cognitive and diagnostic profiles. Full article

Gradable adjectives (long, happy) differ from absolute adjectives (spotted) in that they are dependent on context and speaker/listener perspective for their interpretation. Such context sensitivity may present challenges for individuals with autism spectrum disorder (ASD); however, this has never been investigated for these linguistic elements. In the current study, we asked adolescents with ASD or typical development (TD), who were part of a larger longitudinal study in which autistic characteristics, nonverbal cognition (NVIQ), and standardized language were also assessed, to sort pictures whose properties were either gradable or absolute. Adolescents sorted pictures on two occasions. In the second sorting, we manipulated the context by adding images representing one end of the scale to induce a shift in interpretation. Contrary to prediction, both groups demonstrated sensitivity to the context-specific properties by shifting their cutoffs of what counted as ‘long’ or ‘happy’ when the array was changed. Whereas NVIQ correlated positively with physical property shifts for the TD group, language measures correlated negatively with emotion property shifts for the ASD group. Autistic characteristics were not related to shift patterns in either group. Adolescents with autism are clearly able to take context into account when interpreting gradable adjectives; however, those with better language seem more focused on maintaining their cutoffs more than shifting them. Full article

Background/objectives: The prevalence of autistic spectrum disorder has been increasing rapidly in the world population and the cause of this increase is unknown. Autistic spectrum disorder is an important cause of social, communication and specific learning difficulties in children. Assortative mating may increase the genetic burden leading to manifestation of polygenic diseases affecting mental health in the offspring. Correlation of scores in the social responsiveness scale (SRS), which is used to quantify autistic spectrum disorder features, between spouses, has been used as indicator of phenotypic assortative mating. We investigated whether assortative mating is involved in increased severity of autism spectrum disorder in the offspring. Methods: All studies reporting on investigation of assortative mating in relationship to autistic spectrum disorder were included. Information sources were PubMed, EMBASE and the Cochrane Library. Results were synthesized by entering correlation analyses of results of the SRS conducted in spouses in a meta-analysis. A sub-group analysis was performed comparing spouses with offspring with diagnosed autistic spectrum disorder to spouses without. Prevalence of autistic spectrum disorders in children in countries with and without predominant assortative mating was compared. Results: A total of 14 investigations of assortative mating including 9914 spouse pairs were included. In total, 8 studies (4641 spouse pairs) reported intra-class correlation (ICC) or Spearman’s correlation coefficients between spouses’ SRS scores. There was a significant correlation of SRS scores in studies using ICC or Spearman’s correlation with a pooled coefficient = 0.37. Spouse pairs (n = 401) with offspring diagnosed with autistic spectrum disorder had a pooled ICC coefficient which was 0.278 (95% CI 0.08 to 0.46), significantly lower than spouse pairs without (n = 1525): 0.40 (95% CI 0.35 to 0.46). Higher scores in SRS of both spouses were associated with higher scores and more autism diagnoses in offspring. Pooled prevalence of autistic spectrum disorder in children in countries where assortative mating is most common was 63.1 per 10,000 of population and in countries without it was significantly lower with 14.1 per 10,000 of population. Conclusions: There is evidence of assortative mating according to social responsiveness scale score which correlates significantly in spouse pairs with and without children with autistic spectrum disorder. In countries where assortative mating is predominant, a higher prevalence of autism spectrum disorder in children is found compared to countries without. Full article

Background/Objectives: Phelan–McDermid syndrome (PMS), caused by either chromosome 22q13.3 deletions or pathogenic/likely pathogenic variants in the SHANK3 gene, is a rare neurodevelopmental disorder. Behavioral issues greatly impair the quality of life for affected individuals and their families. This genotype–phenotype study intended to further characterize key behavioral features and their genetic and metabolic correlates in PMS. Methods: We conducted a cross-sectional analysis of data on 56 individuals with PMS. Autistic and related behaviors were assessed with the Autism Diagnosis Interview—Revised (ADI-R) and adaptive behavior skills were assessed with the Vineland Adaptive Behavior Scales-Third Edition (Vineland-3), both covering multiple aspects of communication, socialization and abnormal behaviors. Genetic diagnostic information on deletions or pathogenic variants was supplemented with the sequencing data of nine candidate genes on 22q13.3. Metabolic data were obtained using the Biolog Phenotype Mammalian MicroArray plates (PM-M). Results. Every subject in the cohort presented either prominent autistic behavior or adaptive behavior impairment, 55.4% of them meeting the ASD cutoff in every ADI-R domain and 92.9% scoring in the lowest level of adaptive behavior (range of 20–70). Individuals with SHANK3 variants had lower adaptive behavioral skills than those with 22q13 deletions regardless of deletion size, while genomic parameters were largely unrelated to ADI-R scores. Metabolic profiling identified unique profiles of individuals with PMS compared with controls, while distinct profiles distinguished those who met or did not meet the ADI-R ASD cutoff. Cluster analyses revealed groups of individuals with ASD and other clinical features. Conclusion. This study highlighted the importance of SHANK3 in adaptive behavioral skills and uncovered potential metabolic biomarkers of therapeutic relevance. Full article

Background: Autism Spectrum Disorder (ASD) involves social, emotional, and behavioral challenges, and conventional therapies show limited effectiveness. Aims: To evaluate the effect of Yoga Therapy (YT) on neurophysiological regulation and behavioral functioning in individuals with ASD. Methods: Thirty-six autistic individuals, aged 6 to 25 years and with Childhood Autism Rating Scale (CARS) scores above 15, were randomly assigned to yoga (YG) and control (CG) groups. YG received 60 min YT sessions twice weekly for six months alongside a regular school routine, while CG followed only a regular school routine. Handgrip strength (HGS), visual reaction time (VRT), systolic (SBP) and diastolic (DBP) blood pressure, heart rate (HR), and CARS scores were assessed at pre-, mid-, and post-intervention. Repeated measures ANOVA and Pearson’s correlation were used for statistical analysis. Results: The study showed an increase in HGS (Δ = 3.27 kg) and a reduction in VRT (Δ = −523.86 ms) with a marked decrease in total CARS score (Δ = −5.67), p < 0.01 in YG. There was a mild, non-significant reduction in cardiovascular (CV) dysfunction in YG, while CG showed no significant changes across all measures. Conclusion: Biweekly YT sessions over six months enhanced neurophysiological regulation, improving sensorimotor integration and accelerating cognitive, emotional, and behavioral outcomes in individuals with ASD. Full article

Selective mutism (SM) is an anxiety disorder that prevents speech in certain situations. Increasingly, it is reported that a proportion of those with SM may also be autistic and that physical freezing may be an important feature of SM. Information on speech and freezing behavior in children with a diagnosis of autism only (n = 20), SM only (n = 61), both autism and SM (n = 19), or neither diagnosis (n = 131) was collected via a self-selected cross-sectional online parent survey with an embedded child survey completed by a small subsection of the children (total n = 27: autism only n = 1, SM only n = 13, both autism and SM n = 3, neither diagnosis n = 10). Throat and body freezing were reported by children with SM, whether they were also autistic or not. The most common reasons given by the children that increased their difficulty in speaking were pressure to talk, worries about how they would be perceived, and fear of making mistakes. The Selective Mutism Questionnaire (SMQ) gave the lowest median score for children with both autism and SM, with median scores increasing in the order SM only, autism only, and neither diagnosis. Children who reported more freezing tended to have lower SMQ scores. Full article

In recent years, there has been increasing interest in the study of the gut–brain axis. Furthermore, there appears to be a relationship between abdominal pain, selective eating patterns, emotional instability, and intestinal disorders in Autism Spectrum Disorder (ASD). This work describes the development and accessibility evaluation of the INCE mobile app. This mobile app allows users to obtain levels of gut–brain interaction severity using two scientifically proven scales: The Gastrointestinal Symptom Severity Scale (GSSS) and the Pain and Sensitivity Reactivity Scale (PSRS). The validity of both instruments was established in previous studies in neurotypical and autistic populations. Statistically significant improvements were found following post-design changes in the use and accessibility of the INCE app (.NET Maui 9 Software) reported by professionals (p = 0.013), families (p = 0.011), and adolescents (p = 0.004). INCE represents an important contribution to evidence-based applications and clearly translates into society. Full article

Background/Objectives: Narrative differences in autism spectrum disorder (ASD) and subtle and parallel differences among their first-degree relatives suggest potential genetic liability to this critical social-communication skill. Effective social-communication relies on coordinating signals across modalities, which is often disrupted in ASD. Therefore, the current study examined the coordination of fundamental skills—gaze and speech—as a potential mechanism underlying narrative and broader pragmatic differences in ASD and their first-degree relatives. Methods: Participants included 35 autistic individuals, 41 non-autistic individuals, 90 parents of autistic individuals, and 34 parents of non-autistic individuals. Participants narrated a wordless picture book presented on an eye-tracker, with gaze and speech simultaneously recorded and subsequently coded. Time series analyses quantified their temporal coordination (i.e., the temporal lead of gaze to speech) and content coordination (i.e., the amount of gaze-speech content correspondence). These metrics were then compared between autistic and non-autistic groups and between parent groups and examined in relation to narrative quality and conversational pragmatic language skills. Results: Autistic individuals showed reduced temporal coordination but increased content coordination relative to non-autistic individuals with no significant differences found between parent groups. In both autistic individuals, and parent groups combined, increased content coordination and reduced temporal coordination were linked to reduced narrative quality and pragmatic language skills, respectively. Conclusions: Reduced temporal and increased content coordination may reflect a localized strategy of labeling items upon visualization. This pattern may indicate more limited visual, linguistic, and cognitive processing and underlie differences in higher-level social-communicative abilities in ASD. To our knowledge, this study is the first to identify multimodal skill coordination as a potential mechanism contributing to higher-level social-communicative differences in ASD and first-degree relatives, implicating mechanism-based interventions to support pragmatic language skills in ASD. Full article

Background and Clinical Significance: Adams–Oliver syndrome type 3 (AOS3) is a rare congenital disorder typically characterised by terminal transverse limb defects and variable involvement of other organ systems. Although pathogenic variants in RBPJ are well established in AOS3, associated neurodevelopmental or psychiatric features have been only sporadically documented. Case Presentation: We describe a male patient first evaluated at the age of 10 years and subsequently re-evaluated at 14 years, with AOS3 presenting terminal limb defects together with autistic-like behaviour, cognitive difficulties, dyslexia, and recurrent depressive symptoms. Whole-exome sequencing (WES) identified a heterozygous pathogenic variant in RBPJ (c.505A>G; p.Lys169Glu), confirming the molecular diagnosis of autosomal dominant AOS3. Additional findings included a heterozygous missense variant in CACNA1A (p.Arg1678Cys), a gene linked to neurological disorders with broad phenotypic variability. Because of elevated homocysteine levels, the patient was also tested for MTHFR variants and was found to be heterozygous for C677T and A1298C. Conclusions: This case illustrates a rare combination of a validated AOS3-associated RBPJ variant, along with additional CACNA1A and MTHFR variants that may influence the patient’s neurocognitive and psychiatric characteristics. The results underscore the importance of comprehensive genetic testing in atypical AOS presentations and highlight the complexity of interpreting overlapping genetic factors. Full article