J Neurodev Disord [JOURNAL]
Sun
200 papers
Association between a diagnostic journey in Angelman syndrome and caregivers' quality of life.
Domaradzki J, Walkowiak D
J Neurodev Disord · 2026 Apr · PMID 41975265 · Full text
BACKGROUND: Angelman syndrome (AS) is a rare neurogenetic disease that severely impacts a person’s health and daily living, requiring lifelong specialist care. This places substantial demands on caregivers, leading to a...
BACKGROUND: Angelman syndrome (AS) is a rare neurogenetic disease that severely impacts a person’s health and daily living, requiring lifelong specialist care. This places substantial demands on caregivers, leading to a decline in physical and mental health, financial strain, and reduced quality of life. This study examines the association between a diagnostic journey in Angelman syndrome and parents’ quality of life. METHODS: A self-administered, anonymous, computer-assisted online survey of 120 caregivers was conducted between March and August 2024. The Polish version of the WHO Quality of Life-BREF and the Consumer Financial Protection Bureau Financial Well-Being Scale were used. The collected information was imported into JASP 0.18.3. RESULTS: 54.2% of caregivers experienced difficulties in obtaining timely diagnoses, 51.6% reported receiving misdiagnoses, and 87.4% consulted several specialists before the correct diagnosis was confirmed. Many caregivers believed that a delayed diagnosis harmed their children’s health (31.7%) and resulted in unwarranted or inappropriate hospitalizations (18.3%), medical procedures (26.7%), and medications (16.7%). Caregivers struggled to access genetic counselling and psychological support. AS caregivers had lower quality of life scores compared to the national average across all domains, including social relationships (85.8%), physical health (80.8%), environmental (72.5%), and psychological (61.7%). Caregivers’ quality of life was associated with economic stability, gender, and the timing of diagnosis. CONCLUSION: There is a need for better access to genetic testing, a holistic healthcare approach, and comprehensive support services for caregivers, as well as reliable information, psychological support, financial assistance, and social services.
Altered folate metabolism disrupts auditory function from neonatal vocalizations to adult perceptual precision.
Barda D, Dor L, Sapir H … +7 more , Weinberger S, Mann YA, Or-Zeid A, Baram N, Lederman D, Golan H, Resnik J
J Neurodev Disord · 2026 Apr · PMID 41963776 · Full text
Methylenetetrahydrofolate‐reductase (MTHFR) is a critical enzyme in folate-dependent one-carbon metabolism. While MTHFR polymorphisms have been linked to sensorineural hearing loss and neurodevelopmental disorders in hum...
Methylenetetrahydrofolate‐reductase (MTHFR) is a critical enzyme in folate-dependent one-carbon metabolism. While MTHFR polymorphisms have been linked to sensorineural hearing loss and neurodevelopmental disorders in humans, the translation of early-life metabolic stress into long-term sensory processing and perceptual consequences has remained unclear. Here, we combined neonatal ultrasonic vocalization analysis, adult auditory-brainstem recordings, two-photon calcium imaging of the auditory cortex, and high-resolution psychophysics to map the effects of partial Mthfr deficiency across different developmental stages. MTHFR-deficient pups produced calls with lower onset frequencies and altered temporal structure. In adulthood, MTHFR-deficient mice exhibited elevated auditory brainstem response thresholds and reduced wave I amplitudes, indicating reduced cochlear output. Despite robust cortical tone responses, two-photon imaging revealed significantly broadened frequency–response areas, and a trained cortical activity decoder showed selectively reduced separability for closely spaced tones. Guided by these neural findings, behavioral testing revealed intact discrimination for widely separated tones but impaired performance near the perceptual boundary, indicating reduced fine spectral acuity. Together, these findings outline a developmental trajectory in which early metabolic stress impairs peripheral encoding, central gain compensates for the loss of sensitivity, and perceptual precision is ultimately compromised, highlighting one-carbon dysregulation as a modifiable contributor to auditory dysfunction.
Early neurodevelopmental brain perfusion abnormalities and functional connectivity findings in infants with Prader-Willi syndrome.
Boisgontier J, Charpy S, Pinto G … +12 more , Dangouloff-Ros V, Fillon L, Saitovitch A, Cabet S, Aljabali K, Fabre A, Diene G, Valette M, Cohen D, Zilbovicius M, Tauber M, Boddaert N
J Neurodev Disord · 2026 Apr · PMID 41937185 · Full text
BACKGROUND: Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by distinct eating behaviors that evolve from early feeding difficulties to later hyperphagia. Early brain abnormalities remain poorl...
BACKGROUND: Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by distinct eating behaviors that evolve from early feeding difficulties to later hyperphagia. Early brain abnormalities remain poorly understood, with no data on brain perfusion during infancy. This study investigated early brain perfusion and functional connectivity in infants with PWS and their associations with feeding and social functioning. METHOD: Twenty-seven infants (mean age 3 months) were included in this prospective study. Thirteen genetically confirmed PWS infants (mean age 2.7 ± 1.2 months) underwent 3T multimodal MRI combined with structural imaging, arterial spin labeling (ASL) to quantify cerebral blood flow (CBF) at rest, and resting-state functional MRI to assess functional connectivity. Oral-motor and social functioning were evaluated via the Neonatal Oral-Motor Assessment Scale (NOMAS) and Coding Interactive Behavior (CIB) scale. Group differences in CBF between PWS infants and 14 age-matched controls (mean age 3.5 ± 1.1 months) were investigated via whole-brain voxelwise analysis and linear regression, controlling for age and sex (p ≤ 0.05, FWE-corrected). Within the PWS group, associations between imaging and clinical data were analyzed via age-adjusted linear regressions, corrected for multiple comparisons using the false discovery rate procedure. RESULTS: Compared with controls, infants with PWS presented significantly increased CBF in the insula-superior temporal region, striatum-pallidum, and anterior cingulate cortex (p(FWE) ≤ 0.05). Within the PWS group, the anterior cingulate CBF was significantly associated with oral-motor performance (p(FDR) = 0.04) and birth weight (p(FDR) = 0.03). The functional connectivity between the insula-temporal region and the striatum pallidum was significantly associated with unacylated ghrelin levels (p(FDR) = 0.04), whereas the interhemispheric striatum-pallidum functional connectivity was significantly associated with social functioning (p(FDR) = 0.01). CONCLUSIONS: This multimodal MRI study identified early brain hyperperfusion in infants with PWS, preceding the onset of hallmark symptoms. Perfusion in the anterior cingulate cortex is related to early feeding and growth, and functional connectivity within the insular and striatal regions is linked to social and metabolic measures, suggesting that these associations develop early in life. These findings provide a basis for future longitudinal studies to clarify how early patterns of brain function are related to developmental outcomes.
Mis-spliced FMR1 transcripts in human fragile X syndrome neural progenitors and neurons.
Hourani SM, Utami KH, Oh SL … +2 more , Castrén ML, Pouladi MA
J Neurodev Disord · 2026 Apr · PMID 41923202 · Full text
BACKGROUND: Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by loss of fragile X messenger ribonucleoprotein (FMRP). In most cases, this results from a CGG expansion exceeding 200 repeats in the 5' untra...
BACKGROUND: Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by loss of fragile X messenger ribonucleoprotein (FMRP). In most cases, this results from a CGG expansion exceeding 200 repeats in the 5' untranslated region of the fragile X messenger ribonucleoprotein 1 (FMR1) gene, known as the "full mutation". While the trinucleotide expansion has long been thought to induce epigenetic silencing of this locus, studies have shown that many males with a full mutation still express FMR1 mRNA. However, these individuals produce little to no FMRP protein, due to mechanisms that remain unclear. Mis-splicing of FMR1 transcripts with an expanded CGG tract has recently been proposed as a potential mechanism underlying the absence of FMRP in FXS tissues despite the presence of gene transcripts. METHODS: We used human neural progenitors and neurons differentiated from FXS human pluripotent stem cells and RNA-seq to examine splicing patterns of expanded FMR1 transcripts. We analyzed transcript structure and protein expression to validate mis-splicing mechanisms. RESULTS: We demonstrate an enrichment in levels of mis-spliced transcripts in human neural progenitors and neurons differentiated from FXS human pluripotent stem cells. Our findings confirm that expanded transcripts undergo aberrant splicing, which may contribute to the absence of FMRP despite transcriptional activity. We further show that pharmacological reactivation of the FMR1 locus results in expression of mis-spliced transcripts and that FMRP loss alone, in the absence of an expanded CGG tract, causes only a modest increase in splicing defect. CONCLUSIONS: These results suggest that mis-splicing may represent one of several mechanisms contributing to the absence of FMRP in FXS, specifically in cases where transcriptional silencing of the FMR1 locus is incomplete and expanded transcripts are still produced. In these cases, expanded FMR1 transcripts are produced but undergo aberrant processing that prevents functional protein production. These findings have important implications for understanding FXS pathogenesis and developing therapeutic strategies targeting the expanded locus.
Transient visual evoked potential abnormalities in ADNP syndrome.
Levy T, Silver H, Benrey N … +7 more , Siegel A, Layton C, Zemon V, Gordon J, Buxbaum JD, Kolevzon A, Siper PM
J Neurodev Disord · 2026 Apr · PMID 41922951 · Full text
BACKGROUND: ADNP syndrome is a rare genetic disorder associated with global developmental delay/intellectual disability, autism, aberrant behavior, and medical comorbidities. Sensory symptoms represent a core clinical fe...
BACKGROUND: ADNP syndrome is a rare genetic disorder associated with global developmental delay/intellectual disability, autism, aberrant behavior, and medical comorbidities. Sensory symptoms represent a core clinical feature, even in those without autism spectrum disorder (ASD). Differences in visual evoked potentials (VEPs), an objective measure of excitatory and inhibitory postsynaptic activity, have been reported in other genetic neurodevelopmental disorders and have yet to be examined in ADNP syndrome. METHODS: Transient VEPs (tVEP) were collected from 12 children with ADNP syndrome, 46 autistic children without a known genetic cause, and 19 typically developing children. Time- and frequency-domain variables were compared between groups. RESULTS: Significant differences were found between the ADNP and TD groups in amplitude (P60-N75, N75-P100), latency (P60, N75), and magnitude-squared coherence (MSC). Significant differences were also found between the ADNP and ASD group in latency (P60, N75) and MSC (Band 2, 14–28 Hz). CONCLUSIONS: VEP abnormalities in children with ADNP syndrome compared to an ASD group and controls were identified. Weaker amplitudes in the ADNP group are consistent with prior research in other genetic neurodevelopmental syndromes. Longer latencies and diminished 14–28 Hz band activity, however, are distinct findings and represent an important area of continued study to explore the presence of syndrome-specific VEP profiles. Establishing VEP biomarkers for ADNP syndrome is a critical direction for future clinical trials in the syndrome.
Cognitive deficits linked to intrinsic timescales and gray matter volume abnormalities in children with Duchenne muscular dystrophy.
Niu X, Hu Q, Zhang X … +15 more , Zhang S, Xu K, Xu R, Song Y, Fu H, Zhou Z, Ren Y, Li C, Xu T, Han S, Zhang Y, Xu H, Cai X, Cheng B, Guo Y
J Neurodev Disord · 2026 Mar · PMID 41904378 · Full text
BACKGROUND: Duchenne muscular dystrophy (DMD) is associated with cognitive deficits and neural abnormalities, yet how temporal properties of regional brain activity align with structural changes across development remain...
BACKGROUND: Duchenne muscular dystrophy (DMD) is associated with cognitive deficits and neural abnormalities, yet how temporal properties of regional brain activity align with structural changes across development remains unclear. We integrated intrinsic neural timescale (INT) with voxel-based morphometry (VBM) to explore whether intrinsic timescales disruptions co-localize with gray matter volume (GMV) alterations and relate to cognition in children with DMD. METHODS: Thirty-six children with DMD and 30 age-matched healthy controls underwent T1-weighted MRI and resting-state fMRI. INT and VBM analyses were conducted to assess intrinsic timescales and GMV, respectively. Group differences were tested in statistical parametric mapping toolkit using two-sample t-tests with Gaussian random-field correction (voxel-wise P < 0.001; cluster-wise P < 0.05). Global volumetrics were analyzed with ordinary least squares models including group × age interactions. Spearman rank correlations were subsequently computed to assess associations between cognitive scores and the identified neural abnormalities. RESULTS: DMD showed cognitive impairment and distinct neurodevelopmental features, including: co-localized shorter INT and lower GMV within limbic–sensorimotor networks; widespread GMV reductions across the visual, default-mode, and dorsal attention networks; and divergent age-related trends in global volumes. Moreover, GMV in multiple abnormal regions correlated positively with working memory and perceptual reasoning scores. CONCLUSIONS: These findings suggest that dystrophin deficiency induces co-located functional-structural deficits and aberrant neurodevelopmental trends, offering insights into neurodevelopmental abnormalities in children with DMD. The integration of INT and GMV provides a novel framework for decoding hierarchical network dysfunction and morphological plasticity changes in DMD, identifying potential targets for cognitive intervention.
Phase 2, open-label INSPIRE trial to assess the tolerability and effectiveness of transdermal cannabidiol gel in children and adolescents with 22q11.2 deletion syndrome (ZYN2-CL-031).
Heussler H, Cohen J, Buchanan CB … +2 more , Albers DS, Bzdek KG
J Neurodev Disord · 2026 Mar · PMID 41888667 · Full text
BACKGROUND: 22q11.2 deletion syndrome (22qDS) is a genetic disorder affecting various body systems and associated with behavioral and psychiatric conditions, with no currently approved pharmacological treatments. ZYN002,...
BACKGROUND: 22q11.2 deletion syndrome (22qDS) is a genetic disorder affecting various body systems and associated with behavioral and psychiatric conditions, with no currently approved pharmacological treatments. ZYN002, a transdermal gel containing synthetic cannabidiol, has been demonstrated to be well tolerated, showing potential benefit in related neurodevelopmental disorders. The INSPIRE study evaluated the safety, tolerability, and effectiveness of ZYN002 in children and adolescents with 22qDS. METHODS: INSPIRE was a phase 2, open-label, multicenter trial comprising a 14-week treatment period (Period 1) followed by an optional 24-week, open-label extension (Period 2) for participants with ≥35% improvement on the Aberrant Behavior Checklist-Community (ABC-C) irritability subscale upon Period 1 completion. Participants aged 4 to <18 years with genetically confirmed 22qDS, Clinical Global Impression-Severity score ≥4, and Pediatric Anxiety Rating Scale-Revised (PARS-R) score ≥10, both at Screening and Visit 2 (Day 1), were enrolled. Weight-based, transdermal ZYN002 administration occurred twice daily. Primary outcomes were safety and tolerability, including the incidence of treatment-emergent adverse events (TEAEs). Secondary endpoints included the PARS-R; Anxiety, Depression, and Mood Scale (ADAMS); ABC-C; Clinical Global Impression-Improvement (CGI-I), and Qualitative Caregiver-Reported Behavioral Problems survey. RESULTS: Twenty participants initiated treatment; 17 completed Period 1, and 13 continued into Period 2. ZYN002 was well tolerated; only mild TEAEs were experienced in 35% of participants, and 15% reported treatment-related AEs. Upon Period 1 completion, significant changes from Baseline were observed across all measures: 40.6% PARS-R reduction (P=0.0005); 45.3% ADAMS total score reduction (P=0.0005) with clinically meaningful improvements in all subscales; and significant improvements in all ABC-C subscales, including irritability (36.3%, P=0.0055). On the CGI-I, 75% of participants were rated as “improved” or better relative to Baseline. For the behavioral problems survey, >80% of caregivers reported improvement in ≥1 problem during each period. Anxiety and irritability scores from Baseline through Period 2 maintained a similar reduction to Period 1. CONCLUSIONS: In this interventional, open-label trial of pediatric participants with 22qDS, ZYN002 was considered safe and well tolerated, and was associated with reductions in anxiety-related and behavioral symptoms, supporting further investigation of ZYN002 in a phase 3 randomized controlled trial. TRIAL REGISTRATION: Clinicaltrials.gov (NCT05149898) registered on October 5, 2021.
Electroretinography biomarkers indicate disrupted visual processing in Fragile X syndrome.
Pu Q, Bennett N, Sekhar TC … +2 more , Stanley MT, Berry-Kravis E
J Neurodev Disord · 2026 Mar · PMID 41888648 · Full text
BACKGROUND: Objective physiological biomarkers that index underlying neural circuit dysfunction, such as electroretinography (ERG), are needed in Fragile X syndrome (FXS) research. Fragile X syndrome (FXS) is a neurodeve...
BACKGROUND: Objective physiological biomarkers that index underlying neural circuit dysfunction, such as electroretinography (ERG), are needed in Fragile X syndrome (FXS) research. Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by silencing of the FMR1 gene and loss of fragile X messenger ribonucleoprotein (FMRP), leading to synaptic dysfunction and prominent sensory processing abnormalities. This study evaluated whether ERG waveform differences are detectable in FXS using a handheld RETeval® protocol while accounting for key technical and physiological determinants of signal variability. METHODS: ERG recordings were obtained during routine clinic visits using the RETeval® system in 24 males with genetically confirmed FXS [aged (mean ± SD) 28 ± 10 years; 19 full mutation, 5 mosaic] and 19 neurotypical male controls [aged (mean ± SD) 26 ± 2 years]. Outcomes included flash and flicker ERG parameters (a- and b-wave amplitudes and time-to-peak; flicker amplitude and time-to-peak). Feasibility was assessed using ERG waveform acquisition and success rates. RESULTS: Individuals with FXS demonstrated reduced flash b-wave amplitude (β = −6.84 µV; 95% CI [− 12.87 - −0.81]; p=.026) and prolonged time-to-peak for flash a-wave (β = 1.79 ms; 95% CI [0.32–3.26]; p=.017), flash b-wave (β = 1.10 ms; 95% CI [0.19–2.02]; p = .018), and flicker responses (β = 1.68 ms; 95% CI [0.49–2.88]; p=.006). Flash a-wave amplitude and flicker amplitude were not significantly different from controls. ERG feasibility was substantially reduced in FXS: participant-level flash acquisition and success were 67% and 46% in FXS versus 100% and 100% in controls, respectively (p=.0066 and p=.0001). Participant-level flicker acquisition and success were 46% and 38% in FXS versus 95% and 95% in controls (p=.0003 and p=.0001). No significant laterality effects were observed for waveform parameters or feasibility. CONCLUSIONS: Handheld, light-adapted ERG detected reproducible abnormalities in retinal function in FXS, consistently in reduced flash b-wave amplitude and delayed response timings, supporting altered post-photoreceptor processing as a physiological feature of FXS. Low acquisition and success rates in a routine outpatient clinic workflow indicate feasibility constraints, supporting use of ERG as a context-dependent biomarker for mechanistic studies and interventional trials.
Brain idiosyncrasy during biological-motion perception is amplified in autistic individuals with intellectual impairment.
Cheng M, Hawco C, Yang D … +9 more , Ni HC, Yeh CH, Chang JC, Tu EN, Hsu MY, Wu YY, Chou TL, Gau SS, Lin HY
J Neurodev Disord · 2026 Mar · PMID 41882534 · Full text
BACKGROUND: Neuroimaging research in autism spectrum condition (ASC) often overlooks brain idiosyncrasy by focusing on group averages and frequently excludes individuals with co-occurring intellectual impairment (II). ME...
BACKGROUND: Neuroimaging research in autism spectrum condition (ASC) often overlooks brain idiosyncrasy by focusing on group averages and frequently excludes individuals with co-occurring intellectual impairment (II). METHODS: We investigated functional MRI correlates of passive biological motion (BM) perception, comparing typically developing controls (TDC; n = 33), autistic individuals without II (intellectually able; ASC-IA; n = 28), and autistic individuals with II (ASC-II; n = 19; defined by IQ or adaptive function < 85). RESULTS: While standard group-average analyses revealed the expected BM-sensitive regions (e.g., bilateral posterior superior temporal sulci, cuneus) in the TDC and ASC-IA groups, the ASC-II group showed no consistent group-level activation pattern and exhibited greater activation in the right intraparietal sulcus compared to the ASC-IA group. Using a correlational distance-based metric, we quantified brain idiosyncrasy (“whole-sample brain variability”, VariabilityWhole), representing the deviance of an individual's activation pattern from others. Brain activity in the ASC-II group was significantly more idiosyncratic than the ASC-IA and TDC groups. Furthermore, VariabilityWhole showed significant transdiagnostic correlations with multiple cognitive and behavioural domains relevant to autism, including social difficulties, repetitive behaviours, non-verbal IQ, executive function, sensory hyper/hyposensitivity, ADHD symptoms, and adaptive function. CONCLUSIONS: Key limitations include the cross-sectional design and the use of a passive viewing task without a concurrent behavioral measure to directly link brain findings to task performance. These findings highlight substantial brain heterogeneity within the autism spectrum, particularly in the understudied ASC-II subgroup, and suggest that individual differences in brain processing patterns, rather than solely group-average differences, are critically linked to clinical and cognitive phenotypes.
Beta power as a neural correlate of sensory features in autistic individuals.
Chaudet J, Pichot J, Pedoux A … +11 more , Fleury M, Maruani A, Vantalon V, Humeau E, Bourgeron T, Houenou J, Dumas G, Duchesnay E, Delorme R, Iftimovici A, Lefebvre A
J Neurodev Disord · 2026 Mar · PMID 41851616 · Full text
BACKGROUND: Autism spectrum disorder (ASD) is characterized by social communication difficulties, restricted and repetitive behaviors, and sensory atypicalities. Its pathophysiology remains poorly understood, and no diag...
BACKGROUND: Autism spectrum disorder (ASD) is characterized by social communication difficulties, restricted and repetitive behaviors, and sensory atypicalities. Its pathophysiology remains poorly understood, and no diagnostic biomarker is currently available. However, studies support the hypothesis of an imbalance in the neuronal excitation/inhibition (E/I) balance. Beta and gamma oscillatory powers are described in the literature as indirect electrophysiological features reflecting network dynamics related to this balance. This study takes a dimensional approach to investigate whether alterations in these rhythms are linked to the severity of autistic symptoms. METHODS: A total of 127 individuals with ASD, including a sensory-assessed subgroup of 57 participants, all aged 5 to 17 years, underwent resting-state high-density electroencephalography (HD-EEG) recordings with eyes closed. Absolute power was extracted from the beta and gamma frequency bands for six regions of interest. Multiple linear regression models were used to investigate the relationships between beta and gamma powers and the clinical dimensions of ASD, while controlling for the effects of age and sex. RESULTS: Beta power was positively correlated with sensory hyposensitivity across all regions (all corrected p<.02, n = 57) and with sensory hypersensitivity in the central, parietal, and left temporal regions (all corrected p<.05, n = 57). In addition, an exploratory result suggested that an increase in gamma power may be associated with the severity of restricted and repetitive behaviors (RRBs) in the right temporal region (uncorrected p=.01, n = 127). CONCLUSIONS: These innovative results call for further analysis, including an investigation of other electrophysiological markers providing indirect profiles of E/I balance. Nevertheless, they open new avenues for a better understanding of the neurobiological processes and early diagnosis of ASD.
Longitudinal profiles of executive function in autistic and non-autistic children at high likelihood of autism.
St John T, Corrigan NM, Rokem A … +10 more , Estes AM, Hazlett HC, Pandey J, Schultz RT, Marrus N, Zwaigenbaum L, Lee CM, Dager SR, Piven J, IBIS network
J Neurodev Disord · 2026 Mar · PMID 41820855 · Full text
BACKGROUND: Executive functioning (EF) difficulties are common in autistic children and may aggregate in families. Longitudinal studies examining EF development in autistic children and their siblings are limited. In the...
BACKGROUND: Executive functioning (EF) difficulties are common in autistic children and may aggregate in families. Longitudinal studies examining EF development in autistic children and their siblings are limited. In the current study, we characterized EF development from later infancy through school-age in autistic and non-autistic high likelihood (HL; with an older autistic sibling) and low likelihood (LL; without older autistic sibling) children. METHODS: Participants were 83 autistic and 235 non-autistic HL children, and 132 LL children from the Infant Brain Imaging Study. EF was assessed at ages 12 and 24 months using the A-not-B task and ages 5–14 years (school-age) using the Behavior Rating Inventory of Executive Function (BRIEF), Flanker Inhibitory Control and Attention Test (Flanker), and Dimensional Change Card Sort (DCCS). Longitudinal profiles of EF were examined using linear mixed-effects models with three separate models for each school-age EF outcome. RESULTS: From 12–24 months, the LL group showed an increase in standardized EF scores (p < 0.05). The HL-ASD and HL-noASD groups showed no change (ps > .05). From 24 months to school-age, no change was observed for any group (ps > .05). From 12 months to school-age, standardized scores in the LL group increased (p = 0.002) and in the HL-ASD group (p < .001) decreased for the BRIEF GEC outcome. There were no group differences at 12 months in standardized EF scores (ps > .05) but at 24-months both HL groups had lower scores than the LL group (ps < .05). At school-age, the HL-ASD group had lower standardized EF scores than the LL and HL-noASD groups on all measures (ps < or = .050), and the HL-noASD group had lower standardized scores than the LL group on the BRIEF GEC (p = .014). CONCLUSIONS: Autistic and non-autistic HL children and LL children showed distinct EF profiles. On lab-based measures, autistic and non-autistic HL children showed relatively stable EF performance over time while LL children showed initial improvements. Parent report showed accumulating EF difficulties in autistic HL children. Executive function supports starting in toddlerhood may be useful for HL children showing emerging EF difficulties.
Trajectory of skill acquisition, loss, and regain in females with classic Rett syndrome.
Neul JL, Benke TA, Marsh ED … +4 more , Peters SU, Fu C, Merritt JK, Percy AK
J Neurodev Disord · 2026 Mar · PMID 41820836 · Full text
BACKGROUND: People with Rett syndrome (RTT) have abnormal psychomotor skill development manifested by delay or failure to acquire skills, loss of skills, and potential regain of lost skills. This study aimed to provide d...
BACKGROUND: People with Rett syndrome (RTT) have abnormal psychomotor skill development manifested by delay or failure to acquire skills, loss of skills, and potential regain of lost skills. This study aimed to provide detailed characterization of the frequency, timing, and trajectory of gain, loss, and regain of developmental skills in RTT. METHODS: The occurrence and time of gain, loss, and regain of 51 developmental skills was collected during in-person visits in the RTT Natural History Study from 1228 females with Classic RTT and a pathogenic loss-of-function variant in MECP2. The percentage of participants experiencing gain, loss, or regain events, mean and median age of event and time to event with confidence intervals, and the cumulative incidence curves were calculated and compared to normative data. One-year incidence of either gain or regain of each skill from 0 to 20 years old and one-year incidence of either gain or regain of any of 51 developmental skills was calculated. RESULTS: Across skill domains, acquisition occurred more frequently for lower-level skills than more advanced skills, with a median age of gain before 2 years old and rarely after 6 years old. Loss of previously gained skills occurred in all skill domains, with highest frequency in fine motor and expressive language domains. For most skills, loss occurred early in life and within 2 years of gain, except for loss of gross motor skills which occurred at older ages and further from age of gain. Regain of lost skills was infrequent for most skills, occurred mainly before 6 years old, and within 2 years of loss. After 6 years old, the incidence of either gaining or regaining skills was low. CONCLUSION: These results reveal that most skill gain, loss, and regain in RTT occurs early in life and stabilizes after 6 years old, except for the continued loss of gross motor skills beyond 6 years. The lack of gain or regain of skills beyond 6 years old suggest that any functional gains in these skills after a clinical intervention would represent an important indicator of efficacy as a clinical trial endpoint in RTT.
Crossing the finish line towards a disease-modifying treatment for Angelman syndrome.
Judson MC, de Almeida LP, Burdine RD … +13 more , Chamberlain SJ, Deverman BE, Distel B, Ehlers MD, Jalazo E, Kushner SA, Nespeca M, Sanders SJ, Scheffner M, Yi JJ, Zylka MJ, Elgersma Y, Philpot BD
J Neurodev Disord · 2026 Mar · PMID 41795090 · Full text
Recent progress in the development of genetic therapies promises that impactful treatments for single-gene neurodevelopmental disorders are imminent. But can derailed neurodevelopmental processes be mended after broken g...
Recent progress in the development of genetic therapies promises that impactful treatments for single-gene neurodevelopmental disorders are imminent. But can derailed neurodevelopmental processes be mended after broken genes are replaced or otherwise restored? The results of ongoing clinical trials for Angelman syndrome will soon yield answers to this pressing question, yet the trials face significant obstacles. Here we identify insights needed to aid the quest for a disease-modifying Angelman syndrome therapy, which could serve as a roadmap for the expeditious development of genetic therapies for other single-gene neurodevelopmental disorders.
Anxiety and obsessive-compulsive disorder (OCD) in adults with CHARGE syndrome.
Madhavan-Brown SA, Hartshorne TS, Schneider SB … +1 more , Slavin LJ
J Neurodev Disord · 2026 Mar · PMID 41765890 · Full text
BACKGROUND: CHARGE syndrome is a rare genetic disorder with multiple physical, cognitive, behavioral, and sensory impairments. Anxiety is a common finding. Difficulties with pain, sleep, sensory impairment, communication...
BACKGROUND: CHARGE syndrome is a rare genetic disorder with multiple physical, cognitive, behavioral, and sensory impairments. Anxiety is a common finding. Difficulties with pain, sleep, sensory impairment, communication, daily stress, and unpredictable environments are potential contributing factors to this anxiety. Further research is needed to gain a better understanding of the presentation of anxiety in CHARGE syndrome to promote proper diagnosis and treatment of anxiety. METHODS: An on-line survey was distributed to adults and guardians of adults with CHARGE syndrome. Fifty-two participants provided responses to the Developmental Behavior Checklist-Parent Version, the Florida Obsessive-Compulsive Inventory, and the Generalized Anxiety Disorder 7-Item Scale. Participants also provided demographic data, diagnostic characteristics of CHARGE, their perception of their anxiety, diagnosed mental health disorders, and the frequency of other potential factors of anxiety (i.e. pain and sleep concerns). Descriptive statistics, independent samples t-tests, and Pearson’s correlations provided information on the presentation of anxiety and the relationships between potential factors and anxiety subscale scores. A hierarchical multiple linear regression analysis and mediation analysis were used to investigate if sleep mediates the relationship between pain and anxiety. RESULTS: Generalized anxiety disorder and obsessive-compulsive disorder were the first (39% of sample) and fourth (27% of sample) most common mental health diagnoses reported and 50% of the sample had been diagnosed with at least one anxiety disorder. The most commonly reported anxious behaviors included getting obsessed with an idea or activity, being impatient, getting upset or distressed over small changes in the routine or environment, and being tense, anxious, or worried. Sleep was found to mediate the relationship between pain and anxiety. CONCLUSIONS: This study has implications for understanding the behavioral phenotype of CHARGE syndrome. Based on self-report and legal guardian report, anxiety is a common experience among individuals with CHARGE; generalized anxiety disorder and obsessive-compulsive disorder diagnoses/behavior are the most frequently reported. Further research into the management of pain and improvement of sleep as anxiety interventions for individuals with CHARGE may prove fruitful.
Synchronisation of circadian timing in families and the impact of autism: a scoping review.
Brennan A, Wyse C, Vasconcelos M … +3 more , Rudderham L, Gallagher L, Lopez LM
J Neurodev Disord · 2026 Feb · PMID 41742045 · Full text
Autism Spectrum Disorder (autism) is a neurodevelopmental condition characterised by altered social communication, repetitive behaviours and restricted interests. Emerging evidence suggests that disrupted circadian timin...
Autism Spectrum Disorder (autism) is a neurodevelopmental condition characterised by altered social communication, repetitive behaviours and restricted interests. Emerging evidence suggests that disrupted circadian timing mechanisms may be associated with certain traits of autism, such as sleep difficulties and behavioural dysregulation. Circadian rhythms are primarily entrained by the light–dark cycle but are also shaped by social cues, including synchronisation with the circadian rhythms of family members. Despite growing interest in circadian biology and autism, little is known about how circadian synchrony functions within families that include autistic children. This scoping review synthesises findings on circadian timing in families with autistic and non-autistic children. A systematic search of four databases (PubMed, Scopus, PsycINFO, and CINAHL) yielded 2,423 results, of which 25 met inclusion criteria. An additional 17 studies were identified through handsearching. The final dataset comprised 42 studies, which were organised into a narrative synthesis and thematic analysis. Six studies focused on sleep synchrony in families with autistic children, while the remaining 36 studies examined circadian biomarkers (n = 5), activity rhythms (n = 12), and sleep synchrony (n = 19) in families with non-autistic children. Findings revealed evidence of circadian synchrony in both groups, with family members displaying aligned sleep–wake patterns and daily activity rhythms. However, studies involving autistic families were relatively limited, and the mechanisms underlying circadian synchrony remain poorly understood. While this review highlights emerging insights into circadian synchrony in families, significant gaps in the literature remain. Research in autistic families is particularly scarce, and there is a need for longitudinal and experimental studies to better understand the interplay between genetic, environmental and social factors. Further research should explore whether disrupted circadian synchrony contributes to the neurobiology of autism or its associated traits, such as sleep difficulties and behavioural dysregulation. Addressing these gaps could inform targeted interventions to improve sleep and overall well-being in autistic children and their families.
Oxytocin receptor gene expression in the basal forebrain in autism: association with receptor binding levels and single nucleotide polymorphisms.
Dayley EE, Durham S, Palumbo MC … +2 more , Lundell JF, Freeman SM
J Neurodev Disord · 2026 Feb · PMID 41714951 · Full text
BACKGROUND: The brain’s oxytocin system has been implicated in the neurobiology of autism (ASD), given the role of oxytocin in modulating social function in humans and animals more broadly. Previous work from members of...
BACKGROUND: The brain’s oxytocin system has been implicated in the neurobiology of autism (ASD), given the role of oxytocin in modulating social function in humans and animals more broadly. Previous work from members of our group reported dysregulation in oxytocin receptor (OXTR) binding in postmortem tissue from the basal forebrain in donors with autism compared to unaffected control donors. This study follows up on those findings by investigating the potential genetic and gene expression changes that could be driving those differences. METHODS: We used adjacent sections from the same specimens from our previous study and performed duplex fluorescence in situ hybridization to visualize and quantify OXTR mRNA in the ventral pallidum (VP) and in the cholinergic magnocellular neurons of the nucleus basalis of Meynert (NBM), visualized with choline acetyltransferase (ChAT). We genotyped the brain samples using a SNP microarray on extracted DNA. We then used regression models to test associations between OXTR binding density, OXTR mRNA levels, and relevant OXTR SNPs. Additionally, we tested for correlations between age and OXTR mRNA. RESULTS: ASD specimens showed significantly greater OXTR mRNA than unaffected donors in both the VP and the NBM. Furthermore, this is the first demonstration of OXTR expression in the cholinergic neurons of the human basal forebrain; 73% of OXTR signal in the images of the ChAT+ neurons were colocalized with the cholinergic neurons. OXTR binding levels from our previous study were positively associated with OXTR mRNA in the NBM but only in the ChAT+ neurons there. OXTR binding levels were not associated with OXTR mRNA in the VP. We genotyped all specimens for three common SNPs in the OXTR gene that have been associated with ASD in the literature, but none significantly predicted levels of OXTR binding or gene expression in the NBM or VP. OXTR mRNA levels were strongly positively correlated with donor age across regions, which was driven by ASD specimens. CONCLUSIONS: Taken together, our results contribute to a more nuanced picture triangulating variation in OXTR gene sequence, gene expression, protein levels, and human behavior. TRIAL REGISTRATION: Clinical trial number: not applicable.
Development of at-home video recordings for functional skill assessment in Angelman Syndrome: a pilot study.
Leffler M, Woods RJ, Sapp A … +11 more , Zigler CK, Komorowski R, Crean R, Bird LM, Merton CF, Booman AJ, O'Sullivan JD, Sheehy KA, Duis J, Tan WH, Sadhwani A
J Neurodev Disord · 2026 Feb · PMID 41714940 · Full text
BACKGROUND: Outcome measures currently used to assess function in Angelman Syndrome (AS) may be affected by participant anxiety in the clinic, use of a measure outside of age norms, and a reliance on caregiver report. Th...
BACKGROUND: Outcome measures currently used to assess function in Angelman Syndrome (AS) may be affected by participant anxiety in the clinic, use of a measure outside of age norms, and a reliance on caregiver report. This study aimed to leverage the process used to develop the Duchenne Video Assessment to develop, pilot, and evaluate tasks to be recorded in AS to lay the foundation for the Angelman Syndrome Video Assessment (ASVA), which is being developed for the assessment of everyday functional skills in individuals with AS in their home environment. METHODS: The task list was informed by published conceptual disease models identifying four domains of interest (i.e. communication, motor skills (fine and gross), self-care and executive functioning) and determined by a team of experts based on family and clinician input. The study was conducted remotely in the home environment, with families capturing videos of everyday activities and participating in an exit interview about their experience. Videos were evaluated, and caregiver interview transcripts were coded and analyzed to determine whether each task would be included in the finalized measure. RESULTS: Eleven dyads (i.e., caregiver and individual with AS) completed the study. Individuals with AS between 4 and 39 years of age were enrolled. The video completion rate was 96%, with 99% of the submitted videos meeting quality standards. Caregivers endorsed the value of assessing these individuals in their home environment. The video capture list was reduced to 13 tasks for ambulatory individuals and 12 tasks for minimally ambulatory individuals. CONCLUSIONS: The ASVA is a novel tool that captures data on the daily functioning of individuals with AS in their home environment. If it is validated in the future, this tool presents a promising new approach to evaluate participant functioning in clinical trials and for clinical care.
A symphony of functioning: exploring the interplay of cognition, movement, and visual demands in adolescents on the autism spectrum using mobile brain-body imaging (MoBI).
Nicklas PR, Cruz LN, Terilli C … +5 more , Bojanek EK, De Sanctis P, Freedman EG, Molholm S, Foxe JJ
J Neurodev Disord · 2026 Feb · PMID 41663918 · Full text
BACKGROUND: Autism Spectrum Disorder (ASD) is characterized by differences across multiple intertwined functional domains, including cognitive, sensory, and motor processes. There is a need to understand how concurrent d...
BACKGROUND: Autism Spectrum Disorder (ASD) is characterized by differences across multiple intertwined functional domains, including cognitive, sensory, and motor processes. There is a need to understand how concurrent demands in different domains can impact performances in one another, as the simultaneous processing and execution of tasks from different domains is how most normal daily tasks and activities are completed. Differences in integration are thought to underly many characteristics of ASD, and therefore understanding how the brain processes multi-modal demands in both typically and neurodivergently developing populations is vital, and revealing how neural activity adapts to meet multi-modal demands can serve as valuable markers for supporting diagnosis and treatment decisions.” METHODS: We used Mobile Brain-Body Imaging (MoBI) to simultaneously record 64 channel electroencephalography (EEG), motion-tracking, and response inhibition task performance in adolescents (ages 13–23, mean 16.96 years) who have ASD and typically developing (TD) counterparts. We designed experimental conditions that either did or did not include a motor demand (standing or treadmill walking), sensory demand (static field or optical flow), and cognitive demand (completing task or not) to investigate single, dual, and tri-modal impacts on ERPs, gait kinematics, and task accuracy and speed. RESULTS: The TD group was significantly more accurate when walking. The ASD group did not increase task accuracy despite making similar adjustments to response speed when going from standing to walking. Optic flow did not impact task accuracy or for either group but did impact response speed. Similarly, walking impacted N200 and P300 amplitudes and latencies, but the addition of visual flow did not further these impacts. The ASD group’s neural activity showed differences that were similar in direction but weaker in magnitude to the addition of more demands (walking and flow), compared to the TD group. CONCLUSIONS: There is a complex interplay between motor, cognitive, and sensory functions and we provide evidence here that cross-domain integration of these in adolescents is different in ASD than those who are typically developing. These results suggest that coupled neural and gait responses during multi-modal demands may serve as a potential marker of altered cross-domain integration in adolescents with ASD. Future research should further investigate these relationships with multi-modal methods like MoBI.
A new effective treatment for dyslexia based on dorsal visual stream neuromodulation.
Di Dona G, Zamfira DA, De Benedetto F … +5 more , Turri C, Venturini C, Venniro L, Perani D, Ronconi L
J Neurodev Disord · 2026 Jan · PMID 41620638 · Full text
Developmental dyslexia (DD) affects approximately 10% of individuals, impairing reading ability thus limiting professional fulfilment and psychological wellbeing. DD is associated with both phonological and visual defici...
Developmental dyslexia (DD) affects approximately 10% of individuals, impairing reading ability thus limiting professional fulfilment and psychological wellbeing. DD is associated with both phonological and visual deficits, and the latter are attributed to dysfunctions of the magnocellular-dorsal visual stream, which has a critical role in planning saccades and supporting the extraction of letters/words identity. Currently, there are no effective treatments to restore the brain networks underlying visuospatial analysis and oculomotor efficiency. Adults with DD were enrolled in a randomised clinical trial introducing a non-invasive neuromodulation protocol specifically designed to enhance dorsal stream functionality. We used bi-focal beta-band transcranial alternating current stimulation (tACS) in parietal areas, due to the recognized role of beta oscillation in the dorsal stream functionality. Coupled with a 12-session visuoattentional training, such protocol induced improvements in reading speed, oculomotor control, and visual motion perception. Additionally, beta-tACS led to long-term enhancement of working memory. These outcomes were exclusive or superior to those obtained with a placebo/sham neuromodulation, and were accompanied by plastic changes in the stimulated brain networks. Overall, our findings show the efficacy of multisession tACS in improving core visual, oculomotor and cognitive deficits associated with reading disorders.
Development and validation of the Klinefelter-Associated Neurodevelopmental Difficulties (KAND) Checklist: a three-phase mixed-methods study.
Theelen K, Galasso C, Cools W … +3 more , Gies I, Vanclooster S, Jansen AC
J Neurodev Disord · 2026 Jan · PMID 41618129 · Full text
BACKGROUND: Klinefelter syndrome (KS) (47,XXY) is a genetic condition associated with infertility, hormonal imbalances, and a range of neurodevelopmental and psychosocial challenges, including language impairments, execu...
BACKGROUND: Klinefelter syndrome (KS) (47,XXY) is a genetic condition associated with infertility, hormonal imbalances, and a range of neurodevelopmental and psychosocial challenges, including language impairments, executive dysfunction, and difficulties in social functioning. Although these challenges can significantly affect daily life, no uniform terminology or standardized tool currently exists to systematically identify and assess them. Building upon research in tuberous sclerosis complex (TSC) and using the TSC-Associated Neuropsychiatric Disorders (TAND) Checklist as a foundation, this study explored neurodevelopmental difficulties associated with KS and led to the development, initial validation, and translation of the Klinefelter-Associated Neurodevelopmental Difficulties (KAND) Checklist. METHODS: A three-phase mixed-methods design was used. In Phase 1, a literature review and semi-structured interviews with nine adults with KS and eleven parents identified relevant challenges and informed the preliminary checklist (KAND-PL). In Phase 2, feedback from twenty-four parents and thirteen healthcare professionals, collected through a feedback form and focus group, guided iterative revisions to produce the pre-final version (KAND-PF). In Phase 3, the checklist was evaluated using participant feedback and exploratory psychometric analyses with eighteen individuals with KS and twenty-nine parents. Internal consistency (Cronbach’s α) within conceptually related item groups and correlations with validated behavioral measures (Spearman’s ρ) were examined. Thematic analysis and descriptive statistics were applied to qualitative and quantitative responses. RESULTS: Building on the TAND Checklist, the KAND Checklist addresses KS-specific challenges across 13 domains and a background information section on discussing the diagnosis. Across all phases, input from individuals with KS, parents, and healthcare professionals provided strong evidence for face, content, and response process validity, demonstrating that the checklist covers relevant difficulties, uses clear language, and is feasible for self- and proxy-completion. Internal consistency was good, and preliminary convergent validity was supported through correlations with existing behavioral measures. CONCLUSION: The KAND Checklist is a reliable, accessible tool for identifying neurodevelopmental difficulties in KS. It is intended to raise awareness, facilitate structured clinical conversations, and encourage individualized care. This study highlights the value of participatory research in developing meaningful tools, promoting holistic care, and fostering collaboration between individuals with KS, their families, and professionals. Further dissemination, translation, and larger-scale validation are needed.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe