1. Dainelli A, Nosrati MSS, Romano F, Vercellino F, Mancardi MM, Torella A, Nigro V, Capra V, Zara F, Scala M. Novel De Novo RALA Missense Variants Expand the Genotype Spectrum of Hiatt-Neu-Cooper Neurodevelopmental Syndrome. Mol Genet Genomic Med. 2025; 13(2): e70072.

BACKGROUND: RALA is a small GTPase from the RAS superfamily implicated in signal transduction and cytoskeletal dynamics. Recently, de novo variants in RALA have been associated with a neurodevelopmental syndrome characterized by intellectual disability (ID), developmental delay (DD), and seizures. So far, only < 12 patients have been reported. METHODS: In this study, we report two novel patients with neurodevelopmental impairment and epilepsy carrying previously unreported RALA variants. We performed a thorough clinical investigation of these patients and performed brain MRI to detect potential abnormalities. Trio-exome sequencing and/or NGS panel testing were conducted to identify the genetic variants. Then, we reviewed previous cases reported in the literature. RESULTS: Affected individuals showed a complex neurodevelopmental phenotype consistent with Hiatt-Neu-Cooper neurodevelopmental syndrome. Brain MRI in both subjects showed abnormalities including megalencephaly and ventricular enlargement, previously unreported in RALA patients. Genetic testing revealed two novel de novo missense variants in RALA: c.217G>A, p.(Glu73Lys) in case #1 and c.73G>C, p.(Val25Leu) in case #2. Both variants affect highly conserved residues within the GTP/GDP-binding site of the protein. These changes are predicted to be deleterious by in silico tools, interfering with the GTPase activity of RALA. CONCLUSION: Our findings expand the genotype and phenotype spectrum of Hiatt-Neu-Cooper neurodevelopmental syndrome. Our observations also support the important role of variants affecting the GTP/GDP-binding site of the RALA protein in the pathogenesis of Hiatt-Neu-Cooper neurodevelopmental syndrome.

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2. Galli J, Dusi L, Garofalo G, Brizzi A, Gritti M, Polo F, Fazzi E, Buccino G. Children with autistic spectrum disorder can imagine actions- what can this reveal about the Broken Mirror Hypothesis?. Front Neurol. 2025; 16: 1490445.

OBJECTIVE: This study investigated whether children with Autistic Spectrum Disorder (ASD) can imagine object directed actions similarly to their typically developed (TD) peers. STUDY DESIGN: We tested the ability to imagine goal directed actions in children with ASD (n = 18) and TD (n = 18) peers by means of VMIQ-2 questionnaire and a novel behavioral task, in which children were requested to imagine some daily actions, after seeing them through videoclips presented on a computer screen. Observed actions lasted 4 s and children were requested to follow the same time course during imagination. During this motor imagery (MI) task, children were interrupted at a specific timepoint (e.g., at 1.5 s) from the beginning of the task. Afterwards, they had to select one of two frames extracted from the videoclips: one showed the correct timepoint at which the imagined action was stopped, the other depicted an earlier or later timepoint. Children had to press the key associated to the correct frame to provide their responses. RESULTS: Both groups performed similarly in the questionnaire and in the novel MI task, where they showed the same error rate. Errors distribution suggests that all children exploited a similar strategy to solve the task, being errors mainly distributed in judging the later frame. CONCLUSION: These findings support the view that children with ASD can imagine actions similarly to their TD peers. These results do not fully support the Broken Mirror Hypothesis and may encourage the use of MI as a cognitive strategy in the rehabilitation of autism.

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3. Grant S, Norton S, Hoekstra RA. Central Sensitivity Symptoms and Autistic Traits in Autistic and Non-Autistic Adults. Autism Res. 2025.

Central sensitivity syndromes (CSSs) are a group of health conditions thought to include an underlying sensitisation of the central nervous system. Evidence suggests autistic adults experience poorer physical health than the general population and are more likely to have a CSS. This study examined CSS diagnoses and symptoms in autistic and non-autistic adults, to determine whether CSS symptoms were related to autistic traits, mental health, sensory sensitivity, age or gender. Participants included 534 adults with clinical diagnoses of autism, CSS, both diagnoses or neither (i.e., comparison group), who were recruited through social media, support groups and institutional affiliations. Participants completed online self-report validated questionnaires, including the Autism Spectrum Quotient (AQ), Central Sensitization Inventory (CSI), Sensory Perception Quotient (SPQ), and the PHQ-9 and GAD-7. Autistic people without a diagnosed CSS reported significantly more CSS symptoms than the comparison group, with a mean score above the clinical cut-off. Non-autistic participants with a CSS had significantly more autistic traits than the comparison group. Autistic people with a CSS reported the most sensory sensitivity, with autism only and CSS only groups reporting similar levels of sensory sensitivity and all diagnostic groups reporting more sensory sensitivity than the comparison group. Sensory sensitivity, anxiety, autistic traits, age and gender were all significant predictors of CSS symptoms. The overlap in symptoms between autistic individuals and those with CSS suggests diagnostic overshadowing and possible under-diagnosis or misdiagnosis. Furthermore, these symptoms may exacerbate or mask one another. Notwithstanding potential limitations of representativeness and selection bias, increased awareness of the association between autistic traits and CSS symptoms is important for clinicians to improve diagnostic accuracy and treatment.

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4. Hechler FC, Tuomainen O, Weber N, Fahr F, Karlek B, Maroske M, Misia M, Caruana N. « What does ‘often’ even mean? » Revising and validating the Comprehensive Autistic Trait Inventory in partnership with autistic people. Mol Autism. 2025; 16(1): 7.

BACKGROUND: In this study, we revised the comprehensive autistic trait inventory (CATI)-a self-report inventory of autistic traits, in collaboration with autistic people and provided preliminary evidence for its validity as a self-report measure of autistic traits in the general population. An established strength of the CATI is its ability to capture female autistic traits. Our project aimed to extend this further, to increase the inventory’s accessibility, and to minimise stigma induced by deficit-based representations of autistic experience. METHODS: Together with 22 individuals from the autism and autistic communities, we created the Revised Comprehensive Autistic Trait Inventory (CATI-R). Revisions included rewording items to increase clarity or reduce stigma and expanding items to capture diverse autistic experiences. We also present a series of guidelines for developing self-report inventories of subclinical neurodivergent traits. We validated the CATI-R within a large sample (n = 1439), comprising people with a self-reported autism diagnosis (n = 331), people who self-identified as autistic (n = 44), and non-autistic participants (n = 1046). RESULTS: We successfully validated a revision of the CATI. A confirmatory factor analysis supported the six-subscale structure (two-factor bifactors model: Chi-squared = 2705.73, p < .001, RMSEA = .04, SRMR = .03, CFI = .95, TLI = .94). Spearman's rank correlations showed positive relationships between all subscales (all rs > .56, ps < .001). Convergent validity was demonstrated by significant correlations between the CATI-R and two contemporary inventories of autistic traits: the AQ (rho = .86, p < .01) and BAPQ (rho = .82, p < .01). Finally, a measurement invariance analysis indicated that total-scale scores can be compared across genders. LIMITATIONS: Our study presents only initial evidence for the validity of the CATI-R that should be enriched with further analyses and types of data, including a larger number of participants who do not identify as male or female. CONCLUSIONS: This project provides a revised trait inventory that resonates with actual autistic experience, along with guidelines for creating self-report measures that are sensitive, accessible, and non-stigmatising.

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5. Jamal FN, Dzulkarnain AAA, Basri NA, Rahmat S, Shahrudin FA, Azemin MZC, Sidek SN, Yusof HM, Hamid SRA. Influence of Different Types of Contralateral Suppression Tones on Otoacoustic Emission in Children With Autism Spectrum Disorder. J Audiol Otol. 2025; 29(1): 49-56.

BACKGROUND AND OBJECTIVES: Auditory sensory gating deficits are abnormalities in patients with autism spectrum disorder (ASD) that may lead to sensory processing difficulties. It is particularly difficult for children with ASD to distinguish multiple auditory stimuli, which hinders them from focusing on a single auditory stimulus and separating unnecessary sounds. Suppression of otoacoustic emission (OAE) is an approach used to identify sensory gating deficits in the general population, specifically for children with ASD. This study aimed to investigate the suppression effect of various types of sound suppressors to measure their sensory gating capacity in children with ASD. Subjects and. METHODS: Twenty children including 10 with ASD and 10 normally developing children aged 6-12 years were recruited for this study. One accessible ear was exposed to transient-evoked OAE, whereas the other was exposed to suppressor tones. Contralateral suppressors included white noise, Quranic recitations, environmental noise, and natural sound. The magnitude of OAE suppression was determined from the difference between the OAE amplitude with and without the masker (in dB sound pressure levels) for all sound types. The sound with the highest suppression effect was determined using effect size calculation and repeated-measures analysis of variance at a 95% confidence level. A high suppression effect may suggest a high sensory gating performance, whereas low suppression may indicate low sensory gating performance. RESULTS: Based on the analysis, the sound with the highest suppression effect was that of the waterfall. The suppression results were supported by descriptive analysis findings and effect-size calculations. CONCLUSIONS: This study provides a better understanding of the alternative sound stimuli, besides the standard white noise tone, for the assessment of sensory gating deficits among children with ASD. Sounds with a high suppression effect have the potential to be used as sound therapy interventions for children with ASD as part of rehabilitation and therapy.

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6. Kim YE, Kim M, Kim S, Lee R, Ujihara Y, Marquez-Wilkins EM, Jiang YH, Yang E, Kim H, Lee C, Park C, Kim IH. Endothelial SHANK3 regulates tight junctions in the neonatal mouse blood-brain barrier through β-Catenin signaling. Nat Commun. 2025; 16(1): 1407.

Autism spectrum disorder (ASD) is a neurodevelopmental disability condition arising from a combination of genetic and environmental factors. Despite the blood-brain barrier (BBB) serving as a crucial gatekeeper, conveying environmental influences into the brain parenchyma, the contributions of BBB in ASD pathogenesis remain largely uncharted. Here we report that SHANK3, an ASD-risk gene, expresses in the BBB-forming brain endothelial cells (BECs) and regulates tight junctional (TJ) integrity essential for BBB’s barrier function. Endothelium-specific Shank3 (eShank3) knockout (KO) neonatal mice exhibit male-specific BBB-hyperpermeability, reduced neuronal excitability, and impaired ultra-sonic communications. Although BBB permeability is restored during adult age, the male mutant mice display reduced neuronal excitability and impaired sociability. Further analysis reveals that the BBB-hyperpermeability is attributed to the β-Catenin imbalance triggered by eShank3-KO. These findings highlight a pathogenic mechanism stemming from the ASD-risk Shank3, emphasizing the significance of neonatal BECs in the BBB as a potential therapeutic target for ASD.

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7. Liu V, Hanson E, Owens JW, Hopkin RJ, Shillington A. A Dual Diagnosis of Okur-Chung Neurodevelopmental Syndrome and Becker Muscular Dystrophy: Inquiry Into the Lower Limits of Neurodevelopmental Functioning Attributable to Muscular Dystrophy. Brain Behav. 2025; 15(2): e70276.

PURPOSE: This case discusses the limits of neurodevelopmental functioning attributable to Duchenne’s Muscular Dystrophy (DMD) dysfunction. METHOD: A 3-year-old male presented with global developmental delay, growth failure, and dysmorphic facial features. An SNP microarray revealed an interstitial duplication in exon 55 of DMD suggestive of Becker Muscular Dystrophy (BMD), but his degree of delays led to follow-up exome sequencing revealing a pathogenic CSNK2A1 variant diagnostic for Okur-Chung Neurodevelopmental Syndrome. FINDINGS: Large cohorts predict a full-scale IQ (FSIQ) of 88.3 ± 13.9 among all patients with BMD and 86.1 ± 15.0 among all patients with DMD, while variants impacting the brain dystrophin isoform Dp140 are associated with FSIQ of 77.7 ± 10.8 in BMD and 78.8 ± 18.6 in DMD. CONCLUSION: An FSIQ one standard deviation below these expected ranges should prompt screening for alternative causes of neurodevelopmental delays, and an FSIQ two standard deviations below these ranges should prompt broad-spectrum genetic testing.

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8. Omori M. Increased observation of predictable visual stimuli in children with potential autism spectrum disorder. Sci Rep. 2025; 15(1): 4572.

Children with autism spectrum disorder (ASD) often exhibit social communication impairments and restricted, repetitive behaviors (RRB). Previous studies have shown that children with ASD prefer observing repetitive movements over random movements, reflecting RRB symptoms, but the developmental timeline of this preference remains unclear. New evidence suggests that children with ASD may develop predictive processing abilities for repeated behaviors, providing insight into how they recognize and respond to predictable patterns. This study employed a preferential-looking paradigm to examine whether children with potential ASD demonstrated longer observation durations for predictable movements compared to typically developing (TD) children. Participants were presented with pairs of stimuli featuring predictable and unpredictable movements, which they freely observed side-by-side. Results showed that children with potential ASD spent significantly more time observing predictable movements, particularly during the latter part of the stimulus presentation. These findings suggest that a gradual increase in attention to predictable movements may reflect difficulties in learning cause-and-effect relationships between movement trajectories and the anticipation of complete shapes. This study highlights the potential utility of predictable movement stimuli as a behavioral marker for early ASD screening. It underscores the essential need for further research into predictive processing in children with ASD.

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9. Parsons EM, Hammerstrom MR, Nazaroff A, Kemp M, Montgomery P, Macoun S, Krigolson OE. Analyzing the effects of high autistic traits on neural markers of learning and memory: An EEG approach analysis. Brain Cogn. 2025; 184: 106271.

OBJECTIVE: A body of electroencephalographic (EEG) research demonstrates that executive functioning (EF) differences exist in autistic people. Here, we aimed to investigate how and to what extent these EF differences appear in people with high autistic traits in contrast to a low autistic traits comparison. METHODS: The present study used a series of EEG markers (frontal theta power, frontal beta power, the reward positivity ERP component, and the P300 ERP component) to examine potential differences in EF over the course of gambling and oddball tasks. Qualitative research measures to include the perspectives of the autistic people who took part in the study were also used. RESULTS: While frontal theta and beta power differed between groups, we observed no significant component or correlational differences. However, it was found that high autistic traits participants perceived their task performance as worse than low autistic traits participants despite task performance being equal across groups. CONCLUSIONS: EF differences as measured by frontal theta and beta power were observed across groups. Self-perception of task performance may differ in high autistic traits participants when asked to complete tasks under a time constraint.

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10. Sarangi S, Ranjan Raj R, Rawat A, Salam S, Tripathi S, Aggarwal D, Kashwani R. Oral health care concerns among autism patients: A review. Bioinformation. 2024; 20(9): 1017-21.

Autism is a developmental disorder mostly affecting neural and developmental skills with problems in learning, communication and repetitive behaviour. It has become more highlighted over the past few decades because of the increasing awareness, survey tools and research worldwide. Existing worldwide, this disorder affects the normal lifestyle of the affected people since childhood and continues with the same pace through lifetime. Due to poor neuromuscular coordination, it also affects the normal orofacial dynamics of an individual and manifests as multiple oral disorders. Therefore it’s of interest to report known data on the oral manifestations of this spectral disorder and various approaches at varied levels to maintain a harmonious oral environment.

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