Autism spectrum disorders (ASD) represent a substantial social problem affecting at least 1 in 100 children worldwide. These conditions are very often accompanied by intellectual disability (ID) and speech delay; thus, they can be considered within a clinical continuum of neurodevelopmental disorders. Given the high heterogeneity of ASD, the subjective nature of diagnostic criteria, and the presence of phenocopies, identifying genetic determinants of these disorders remains a challenge. To investigate the spectrum and frequency of rare genetic variants in genes with proven association with ASD in Russian children. 110 patients from 106 families were recruited into the study (mean age at diagnosis 6 years; boy-to-girl ratio 3:1. Most of the patients (84%) demonstrated a combination of ASD with developmental delay (DD) or ID. Patients with syndromic features were subjected to the chromosomal microarray analysis. The remained children underwent clinical exome sequencing aimed at identifying presumably monogenic causes of ASD. The study focused on rare (minor allele frequency ≤ 0.001) variants affecting high-confidence ASD-associated genes. Pathogenic copy number variations were detected in three (7%) of the patients examined. Clinical exome sequencing revealed pathogenic/likely pathogenic variants in 12 of 105 cases (11%), indicating the presence of monogenic syndromes with established clinical significance (Pitt-Hopkins syndrome, ZTTK syndrome, syndromic X-linked ID of Billuart type, Snijders-Blok-Campeau, Helsmoortel-van der Aa, Coffin-Siris, Clark-Baraitser, Keefstra syndromes, etc.). In addition, 27 patients (26%) had 37 rare variants of unknown clinical significance in DSCAM, SHANK2, AUTS2, ADNP, ANKRD11, APBA2, ARID1B, ASTN2, ATRX, SCN1A, CHD2, DEAF1, EHMT1, GRIN2B, NBEA, NR4A2, TRIO, TRIP12, POGZ, EP300, FOXP1, PCDH19, GRIN2A, NCKAP1, and CHD8 genes. No specific variant was detected more than once in unrelated patients. Among the genes with rare variants found in 2 or more patients were TRIP12 (n = 4), AUTS2 (n = 3), ARID1B (n = 3), PCDH19 (n = 3), EP300 (n = 3), TRIO (n = 2), ASTN2 (n = 2), EHMT1 (n = 2), and CHD2 (n = 2). Of note, 5 male ASD/DD patients from 3 unrelated families had PCDH19 missense variants, confirming that at least some hemizygous males with non-mosaic PCDH19 variants may present with neurobehavioral abnormalities. These variants did not cause epilepsy restricted to females in patients' mothers or sisters. These data confirm a tremendous diversity of genetic causes of ASD. Clinical exome sequencing may serve as a reasonable alternative to whole-exome sequencing.

Purpose The COVID-19 pandemic created a rapid move to digital delivery of services within the NHS. Reduced face-to-face contact for the general population meant accessing services through video or telephone calls; this was not possible for some service users with intellectual disabilities. Technology, originally designed for use with older adults to reduce isolation, was trialled by the learning disability (LD) service in an NHS Trust. The pilot was exploratory, giving staff and service users the opportunity to experiment and find potential uses for equipment initially designed for a different client group. This evaluation aims to review how staff utilised the equipment, its benefits and drawbacks. Design/methodology/approach Semi-structured interviews were carried out with staff and service users to explore the possibilities of remote service delivery with this patient group. Interview data was coded, themed and analysed. Findings Devices were well received once technical issues were resolved. The trial was successful in reducing isolation and delivering some services in a new way at a time of mandatory social isolation. The move to digital service delivery has not stopped post-pandemic and has enhanced choices available for clinicians. This may improve service access for vulnerable communities with limited access to mainstream IT. Originality/value This study highlights how technology can be used to support access to services amongst vulnerable groups. Further research into patient experience of using devices should be considered to develop evidence of their usefulness in delivering services and reducing isolation across services.

Cardiorespiratory fitness is a crucial component for health. However, measuring cardiorespiratory fitness in older adults with intellectual disabilities (ID) in practice and in large-scale studies remains challenging. The Two-Minute Step Test (2MST) is a submaximal cardiorespiratory fitness test that is brief, relatively easy to perform, and does not require any expensive materials. However, the clinimetric properties of the 2MST for older adults with ID are unknown. Therefore, this study aimed to determine the feasibility, reliability and convergent validity of the 2MST in older adults with ID. This was a cross-sectional study within the 'Healthy Ageing and Intellectual Disabilities' (HA-ID) cohort study. Participants (n = 180, 70.6 [66-75] years) that participated in the physical fitness assessment were included in this study. Feasibility was defined as a successful completion according to protocol. Test-retest reliability was assessed over two measurements, on the same day, with the intraclass correlation coefficient (ICC). Convergent validity was assessed relative to other fitness components (static balance, muscular endurance, comfortable and fast gait speed), with Pearson's and Spearman's correlation coefficients. The 2MST showed moderate feasibility for the first (49.4%) and second (48.3%) measurement. Feasibility was good in participants with borderline, mild and moderate ID (57.1%-80%), but low in participants with severe (15.2%) and profound ID (7.7%). Test-retest reliability was excellent (ICC = 0.88). The 2MST had a moderate correlation with static balance (r = 0.46) and comfortable (r = 0.42) and fast (r = 0.51) gait speed, and a good correlation with muscular endurance (r = 0.63). Based on predefined criteria, all correlations were at least moderate (r > 0.30), supporting good convergent validity (categorised as good if three or more out of four correlations were at least moderate). The 2MST is a feasible, reliable and valid test to use in older adults with ID. Feasibility was especially good in older adults with borderline to moderate ID; however, it was low in adults with more severe ID. The excellent test-retest reliability and good indications for convergent validity show this test is a suitable field test for cardiorespiratory fitness to use in older adults with ID.

A missense mutation in the MTSS2 gene, which encodes the I-BAR domain protein ABBA (Mtss1l/Mtss2), has been linked to an intellectual disability syndrome. To better understand the MTSS2 mutation-related effect in the brain, we elucidated the cells expressing ABBA and the localization of ABBA in these cells to get insights into which cells and processes might be dysfunctional in mutation-carrying patients. As a novel discovery, we found that ABBA was highly expressed in GABAergic inhibitory neurons, such as parvalbumin-positive interneurons in the hippocampus. At the subcellular level, ABBA localizes to the edges of membrane protrusions in various cells in the brain, suggesting a role in cell migration and spinogenesis. Overexpression of ABBA in pyramidal excitatory and inhibitory neurons increased dendritic spine density. Through live-cell imaging, we demonstrated that ABBA facilitates spine initiation by clustering on the plasma membrane before a new filopodium appears. However, our live cell imaging data also revealed that ABBA localized not only to small focal points, typical for filopodia formation, on the plasma membrane, but also more broadly on the edge of lamellipodial structures. Compared to its close homolog MIM, ABBA appears to be a more general facilitator of protrusion formation, from dendritic filopodia to lamellipodial structures. Altogether, our findings provide insights into ABBA expression, localization, and functional mechanisms, advancing our understanding of its role in neurodevelopmental processes and disorders.

To address the dearth of literature on outcomes for autistic individuals with significant intellectual disability, researchers require validated measures to use in research. This study examined the psychometric properties of PROMIS quality-of-life caregiver-proxy scales included in the PROMIS Autism Battery-Lifespan among autistic children who are minimally verbal and with intellectual disability (MVID). We examined basic psychometric properties of the PROMIS caregiver-proxy scales and tested the scales for measurement invariance between groups of autistic children who are minimally verbal with intellectual disability and those without signficant intellectuatl disability (N = 448). We also descriptively examined feedback from caregivers regarding the appropriateness of the questions to capture meaningful outcomes for their autistic children who are minimally verbal with intellectual disability. Results indicated that some PROMIS caregiver-proxy scales (Anger, Positive Affect, and Life Satisfaction) exhibited strong psychometric evidence and content validity, but many other scales either did not demonstrate measurement invariance between groups or included a high proportion of items endorsed by caregivers as not applicable for their minimally verbal autistic child. Our findings emphasize the need for continued work developing appropriate measures for capturing meaningful outcomes among minimally verbal autistic people with significant intellectual disability.

Background: This research emphasizes the background issue of social media-based adverse effects on children with intellectual disabilities in Saudi Arabia, along with parents’ perceptions and possible solutions for mitigating such issues. Results: The results derived from the survey method used with Saudi parents indicated that social media had negative emotional, physical, and psychological impacts on children suffering from intellectual disabilities. Parents’ perceptions are also negative of these children’s excessive usage of social media Conclusions: It is concluded that parents must guide these children to limited and positive usage of social media for exchanging information and educational achievements. Parents are also required to keep their children monitored and use the co-surfing of social media accounts to prevent children from cybercrimes, fake relationships, and data privacy issues.

Menstrual hygiene, caregiver challenges, and human rights concerns for adolescent girls with intellectual disabilities: a state-of-the art review

Objectives: This study aimed to assess the caries experience and severity among students with disabilities in Sokoto, Nigeria. Materials and Methods: This descriptive cross-sectional study was conducted on elementary and high-school students with special needs attending Abdulrasheed Adisa Raji Special School in Sokoto State, Nigeria, who were selected by a systematic random sampling method. The students were between 6 to 28 years, and had hearing, visual, intellectual, or physical disabilities. Data regarding their sociodemographic characteristics were collected using a questionnaire, and their dental caries experience was determined by using the decayed, missing, and filled teeth (DMFT) index. SPSS version 23 was used for data analysis with a statistical significance set at 0.05. Results: Sixty-nine females (29.2%) and 167 males (70.8%), totaling 236 students, with disabilities participated in this study. The mean DMFT score was 0.72±1.32. Children between 6-12 years had the highest caries experience (mean DMFT=0.92±1.17). Among different disability groups, those with intellectual disability had the highest rate of caries experience (mean DMFT=0.98±1.61). Males had a higher rate of dental caries experience than females (P=0.006). The decayed component (DT) had by far the highest mean score (0.66±1.26) compared to other DMFT components. Conclusion: The caries experience of the study population was low. Nonetheless, the severity of caries was high in those who had caries experience.

The assessment of adaptive functioning is essential in neurodevelopmental disorders, such as Intellectual Disability (ID) and Autism Spectrum Disorder (ASD), as a diagnostic criterion and as a definer of the level of severity or support. The Adaptive Functioning Scale (Escala de Funcionamento Adaptativo - EFA) is a Brazilian instrument for assessing adaptive functioning in children and adolescents aged 6 to 15. This study aimed to investigate evidence of the validity of EFA criteria as a screening instrument FA difficulties in individuals with ID and ASD. 917 EFA children and adolescents without diagnoses of neurodevelopmental disorders participated, 76 with a diagnosis of ID, and 65 with ASD. Variance analyses indicated differences in Z values in the three dimensions for the three groups. The differences presented a medium effect size, with the following partial Eta squared values: Social = 0.40; Practical = 0.43; Conceptual = 0.58. Sensitivity values ranged from 90 to 91% and 87 to 94%, while specificity values ranged from 64 to 74% and 63 to 90% in the ASD and ID groups respectively. The AUC values obtained for the EFA indicate that it has an excellent discriminatory capacity between the different aspects of adaptive functioning in the three domains of the instrument. The EFA showed a greater ability to identify individuals with ASD and ID compared to individuals without diagnosis for all domains.

Introduction: Caregivers of children with Neurodevelopmental Disorders (NDDs) experience a multidimensional burden that affects their physical, emotional, social, and financial well-being. This burden is intensified in contexts marked by social vulnerability, limited specialized services, and persistent stigma. Symptom severity — such as autism, intellectual disabilities, and complex comorbidities — further increases caregiving demands. This article aims to discuss the nature of caregiver burden among parents of children with NDDs, examining the factors that shape it and the intervention strategies suggested in recent literature. Methods: An integrative literature review was conducted following a structured methodological framework. Articles published between 2015 and 2025 were identified in PubMed using descriptors related to caregiver burden and neurodevelopmental disorders. Results: Eighteen studies met the inclusion criteria. Findings consistently indicated high levels of psychological distress, fatigue, sleep disturbances, and social isolation among caregivers. Interventions such as telehealth, peer support, and family-centered practices demonstrated positive outcomes in reducing stress and strengthening resilience. Discussion: The analysis shows that caregiver burden arises not only from clinical demands but also from structural factors, including inequitable access to services and insufficient public policies. Resilience-promoting strategies and multiprofessional support can mitigate these effects, but they remain underutilized in underserved settings. Conclusion: Caregiver burden represents a significant public-health concern requiring intersectoral action. Strengthening inclusive policies, expanding access to specialized and telehealth services, and improving professional training are essential to support caregivers and promote better developmental outcomes for children with neurodevelopmental disorders.

Neurological disorders affect both the central and peripheral nervous systems, exhibiting broad genetic and clinical variability and posing a significant public health concern. These conditions range from common disorders, such as attention deficit disorder and epilepsy, to rare diseases like intellectual disability (ID) and white matter disorders. Exome sequencing (ES) has emerged as a powerful tool in diagnosing the genetic underpinnings of these disorders. ES demonstrated its feasibility as a cost-effective diagnostic pathway by identifying pertinent diagnostic outcomes in 29.4% of cases and being noticeably more cost-effective than conventional genetic diagnostic techniques. This study investigated the genetic basis of three rare neurological disorders in three unrelated Pakistani families using ES. Each family presents with a distinct syndromic form of ID, associated with bilateral frontoparietal polymicrogyria (BFPP) (Family-1), Li-Ghorbani-Weisz-Hubshman syndrome (LIGOWS) (Family-2), or hypomyelination and congenital cataract (HCC) (Family-3). The functional consequences of the missense variants were investigated using bioinformatic prediction tools to confirm the pathogenicity. In Family-1 with BFPP, ES identified a novel homozygous missense variant ((NM_001145771.3): c.1579C>T; (NP_001139243.1): p.Pro527Ser) in ADGRG1, predicted to impact protein function. In Family-2 with LIGOWS, a novel homozygous missense variant ((NM_182958.4): c.649A>C; (NP_892003.2): p.Met217Leu) was found in KAT8. In Family-3 with HCC, a novel homozygous nonsense variant ((NM_032581.4): c.722T>G; (NP_115970.2): p.Leu241Ter) was identified in FAM126A, likely resulting in a truncated, nonfunctional protein. Families' structures and segregation analysis confirm disease condition segregating with autosomal recessive mode of inheritance. The functional consequences of the ADGRG1 and KAT8 missense variants were revealed as deleterious using bioinformatic prediction tools. We have identified novel pathogenic variants in ADGRG1, KAT8, and FAM126A in individuals with rare neurological disorders, thereby expanding the genetic and clinical spectrum of these conditions. This study reports, for the first time, an autosomal recessive inheritance pattern for a KAT8-related disorder, providing new insights into its genetic architecture.

A comprehensive synthesis of the broad range of neurodevelopmental and psychiatric manifestations in NF1 is needed to identify knowledge gaps and future directions for NF1 research. In the following scoping review, we identify and summarize the scope of research that examines neurodevelopmental and psychiatric manifestations, both as categorical diagnoses and symptoms, in children and adolescents with neurofibromatosis type 1 (NF1). As a secondary objective, we summarize studies examining the association between intellectual impairment and psychopathology in children and adolescents with NF1. A literature search was conducted in three databases (Medline, PsychINFO, EMBASE) from inception to the third week of November 2024 with no restrictions on year of publication or publication type. Search terms related to neurofibromatosis, psychiatric symptoms and disorders, intellectual disability, and learning disorders. A total of 112 studies were identified that met the review inclusion criteria. The majority of studies focused on children aged 6-12 years (n = 106; 95%) and adolescents (n = 87; 78%) with fewer studies in the preschool age (n = 43; 38%) and the least number of studies in the infant age group (n = 10; 9%). The majority of these involved clinical cohorts (n = 94; 84%). The intellectual domain was assessed in 77 studies (69%), the academic domain in 29 studies (26%), and the psychiatric domain in 88 studies (79%). Thirteen studies (12%) assessed all three domains (intellectual, academic, and psychiatric). Many studies assessed for ADHD diagnosis (n = 24; 21%) or symptomatology (n = 43; 38%) or for autism diagnosis (n = 12; 11%) or symptomatology (n = 26; 23%). Few studies assessed for anxiety diagnosis (n = 4; 4%) or symptomatology (n = 7; 6%) or for depression diagnosis (n = 4; 4%) or symptomatology (n = 7; 6%). Twelve studies (11%) examined the association between intellectual impairment and psychopathology. There is a need for studies that use standardized assessments to reliably distinguish between traits and diagnoses and to capture whether children meet criteria for more than one disorder (co-morbidity). There is also a need for studies examining the association between intellectual impairment and psychopathology in children with NF1. A better understanding of the neurodevelopmental and psychiatric manifestations that children with NF1 are at greatest risk for can help shape clinical care guidelines, improve parental psychoeducation, and optimize the use of effective interventions.

The effects of perceptual-motor exercises on executive functions and motor skills in children with intellectual disabilities: a randomized cluster trial

Both hospitalised (H) and non-hospitalised (NH) individuals may have different symptoms and impairments after COVID-19. We aimed to explore symptoms, mental and physical health after initial COVID-19 for both groups of individuals and the association between physical and mental impairments in relation to self-rated health status and to identify different cluster profiles. Participants were recruited between June 2020 until December 2022 at the Karolinska University Hospital, Sweden. Data was collected at first assessment after COVID-19 and consisted of demographics, medical history, symptoms and results from physical function tests and self-reported questionnaires. Here we show that among 931 participants, the H-group are older (mean age 56.7 years) and predominantly male (72%), while the NH-group are younger (mean age 44.4 years) and mostly female (84%). Fatigue, dyspnoea, joint pain, paraesthesia, and chest pressure are common symptoms reported across all participants. Physical function is lower than predicted in both groups and the NH-group have higher prevalence of depression and fatigue. These impairments together with dyspnoea, number of symptoms and sick leave are also associated with reduced self-rated health. Four specific cluster profiles have been identified, and 66.4% of the participants have severe to moderate impairments. Regardless of the initial level of care approximately two-thirds of the participants exhibit various physical and mental impairments associated to self-rated health after COVID-19. We propose that defining specific cluster profiles is crucial for tailoring management of post-COVID sequelae. Further long-term studies are needed to understand recovery trajectories to optimise targeted interventions.

Actigraphy is being increasingly used to assess sleep and circadian rhythms among populations with intellectual and developmental disabilities and genetic syndromes, including Rett syndrome and related disorders, but the reliability of these measures in these populations is unclear. The primary purpose of the current study was to evaluate the impact of recording duration on the reliability of various measures of sleep and circadian rhythm in Rett and related syndromes. Two 14-day recordings were collected between 4 and 12 weeks apart in a sample of 30 individuals (aged 2-36 years; 97% female). Reliability was estimated by calculating statistics based on 3, 5, 7, 10 or 13-14 nights of recording. Most measures of average sleep quality could be reliably estimated with 7-10 nights. Measures of night-to-night variability in sleep timing showed poor reliability at all recording durations, whereas night-to-night variability in sleep duration showed adequate reliability at 5-7 days of recording. The reliability of measures of circadian rhythm was highly variable. The results suggest that the optimal recording durations for actigraphy in this population vary based on the specific metrics of interest, but most can be measured reliably.

Researchers’ Roadblocks to Including People with Intellectual and Developmental Disabilities (DD) in Research: Translational Science and/DD Program Leaders Insights

Exploring programme theory when integrating ICF categories in a support development programme for children with intellectual disability living in special residences: a realist evaluation

15q26 deletion syndrome is a rare genetic condition caused by the deletion of terminal end of the long arm of chromosome 15 (Drayer's syndrome). Clinical presentation usually implies intrauterine growth restriction, postnatal growth failure, varying degrees of intellectual disability, developmental delay, typical facial appearance, brachydactyly and diaphragmatic hernia. Lymphangioleiomiomatosis (LAM) is a rare genetic disease affecting multiple organs, which almost exclusively afflicts women. Typical presentation of LAM disease is pulmonary LAM, characterized by cyst-like destruction of pulmonary tissue, which leads to loss of pulmonary function, and if progresses further can lead to recurring pneumothoraxes. Co-existence of these two rare diseases hasn't been reported so far. Here we report a case of the simultaneous presence of 15q26 deletion syndrome and LAM disease in a 38-year-old female. She presented with short statue, brachydactyly, pes equinovarus, microcephaly and signs of intellectual disability manifesting from birth and early childhood. At the age of 23 she starts to suffer of recurring pneumothoraxes with gradual loss of pulmonary function. CT and pathohistological findings revealed the presence of pulmonary LAM and genetic testing revealed 15q26.2 microdeletion characteristic for 15q26 deletion syndrome. Successful treatment of LAM using mTOR inhibitor Sirolimus resulted in clinical and functional improvement.

Genotype-phenotype analysis of pathogenic copy number variations in pediatric epilepsy.

ABSTRACT This paper offers a critique of nascent efforts to reclaim the r-slur—referred to throughout the manuscript as the r-word so as not to beg the question of its normative status—grounded in Linda Martín Alcoff’s groundbreaking ‘The Problem of Speaking for Others’. In it, I argue that the question of the r-word’s reclamation fails to take into account the intra-community hierarchies that are reified when only some members of a slurred community—in this case, the community consisting of neurodivergent people and those with intellectual disability, as well as others targeted by the r-word—are able to participate in a slur’s reclamation. I begin by discussing slur reclamation more generally, before using Alcoff’s work, alongside the writings of Emmalon Davis and Olúfẹ́mi O. Táíwò, to show why the reclamation of the r-word is fundamentally different than that of other slurs.