Search Results (336)

Zinc finger proteins are frequently implicated in a wide range of neurodevelopmental disorders (NDDs). In this study, we report a case of mild intellectual disability (ID), global developmental delay (GDD), and developmental coordination disorder (DCD) in an individual with unaffected parents. Trio-based whole-exome sequencing (WES) identified a de novo variant (c.1530dup, p.Glu511ArgfsTer16) in the ZNF496 gene of the proband. According to ACMG guidelines, this novel variant is classified as pathogenic. It creates a frameshift that introduces a premature stop codon, resulting in a truncated protein of 525 amino acids (compared to the wild-type 587 residues). Notably, NMDEscPredictor analysis predicted that the transcript escapes nonsense-mediated decay (NMD) despite the frameshift. Computational analyses suggest the potential pathogenetic effects of the identified variant. As documented, ZNF496 interacts with JARID2, a gene associated with NDDs, ID and facial dysmorphism (MIM: #620098). In silico analyses suggest that the identified mutation disrupts this interaction by deleting ZNF496’s C2H2 domain, potentially dysregulating JARID2 target genes. To our knowledge, this is the first reported association between ZNF496 and NDDs, and the variant has been submitted to the ClinVar database (SCV006100880). Functional studies are imperative to validate ZNF496’s role in NDDs and confirm the mutation’s impact on ZNF496-JARID2 interactions. Full article

Background: More than 1500 genes are associated with developmental delay and intellectual disability, with variants in many of these genes contributing to a shared phenotype. The discovery of variants of uncertain significance (VUS) found in these genes during genetic testing can lead to ambiguity and further delay in diagnosis and medical management. Phenotyping, additional genetic testing, and functional studies can all add valuable information to help reclassify these variants. Here we demonstrate the clinical utility of epigenetic signatures in prioritizing variants of uncertain significance in genes associated with developmental delay (DD) and intellectual disability (ID). Methods: Genome sequencing was performed in a male with developmental delay. He was found to have VUSs in both PHF6 and DDB1 genes, linked with Börjeson–Forssman–Lehmann syndrome (BFLS) and White–Kernohan syndrome (WHIKERS), respectively. These two disorders share a similar phenotype but have distinct inheritance patterns and molecular pathogenic mechanisms. DNA methylation profiling (DNAm) of whole blood was performed using the clinically validated EpiSign assay. Results: The proband’s methylation profile demonstrated a strong correlation with the BFLS methylation signature, supporting the PHF6 variant as a likely cause of his neurodevelopmental disorder. Conclusions: Epigenetic testing for disorders with distinct methylation patterns can provide diagnostic utility when a patient presents with variants of uncertain significance in genes associated with developmental delay. Epigenetic signatures can also guide genetic counselling and family planning. Full article

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

Individuals with Autism Spectrum Disorder (ASD) often experience sensory hyperreactivities that interfere with daily life activities. White noise, characterized by its uniformity and its ability to mask environmental sounds, may serve as a tool to improve sensory and emotional regulation in children with ASD. The primary objective was to evaluate the response to white noise in improving self-regulation in minors with ASD. As a secondary objective, the study assessed whether there were differences in the response to white noise between patients with ASD and those with ASD and Intellectual Disability (ID). This study was conducted in the Child and Adolescent Psychiatry and Psychology Department of Hospital Clínic of Barcelona. A total of 54 patients, aged between 7 and 17 years, were included. The patients were divided into two groups: Group 1 consisted of patients diagnosed with ASD (n = 21), and Group 2 included patients diagnosed with ASD and ID (n = 33). White noise was offered to the patients, and their response was evaluated before and after the exposure using the Conners Teacher Rating Scale. Overall, the response to white noise in the sample was positive, with a significant difference in scores on the Conners Teacher Rating Scale (p < 0.001). When dividing the sample into the ASD group and the ASD + ID group, it was observed that the ASD + ID group tolerated white noise better and had a longer exposure time, although both groups showed improved scores on the Conners Teacher Rating Scale. White noise may be a valuable tool to enhance well-being in individuals with ASD, reduce motor restlessness, and increase attention span and emotional stability. However, its effectiveness varies across individuals. It is recommended to tailor its use to individual needs and to extend future research by incorporating physiological measures and larger sample sizes. Full article

Biallelic pathogenic variants in DHCR7 result in decreased activity of 7-dehydrocholesterol (7-DHC) reductase, which converts 7-DHC to cholesterol, and causes Smith–Lemli–Opitz syndrome (SLOS). Elevated serum 7-DHC levels are indicative of SLOS as are intellectual disability (ID), growth retardation, microcephaly, craniofacial anomalies, and 2–3 toe syndactyly. Additional congenital malformations may be present in SLOS, and broad clinical variability has been recognized in SLOS. Rarely, biallelic pathogenic DHCR7 variants were reported with low-normal and normal intelligence quotient (IQ) and development. We report here a pair of siblings with mild global developmental delay, infrequent epileptic seizures, and elevated serum 7-DHC levels, associated with the homozygous DHCR7 variant c.988G>A (p.Val330Met). Remarkably, neither sibling displayed congenital anomalies nor dysmorphisms. Quattro-exome sequencing performed for global delay and mild ID in both siblings did not identify other ID causes. c.988G>A affects a highly conserved amino acid and displays a relatively high global population allele frequency of 0.04%, with absence of homozygotes from the population database gnomADv4.1.0. Our observation leads us to suggest that DHCR7 variant c.988G>A and other DHCR7 variants might be generally considered as underlying non-syndromic ID. Full article

Background/Objectives: Family self-care (FSC) is increasingly recognized as a vital aspect of caregiving in pediatric chronic conditions. However, its development in families of children with intellectual disabilities (IDs) remains underexplored. This study aimed to examine how families construct and sustain FSC, and to identify factors that shape its development across four domains: physical, cognitive, psychosocial, and behavioral. Methods: A qualitative study was conducted using an abductive approach, combining inductive thematic analysis with a deductively applied theoretical framework. Semi-structured interviews were carried out with nine families of children with ID in southern Portugal. The children ranged in age from 4 to 15 years, and the parents were aged between 29 and 53 years. The data was analyzed using Bardin’s content analysis, supported by NVivo software, and organized according to the FSC framework. This study followed COREQ guidelines. Results: The families described a range of self-care strategies, including environmental adaptations, experiential learning, emotional regulation, and long-term planning. These practices were shaped by contextual factors such as access to healthcare, relationships with professionals, emotional support networks, and socioeconomic conditions. Four emergent conclusions illustrate how structural and relational dynamics influence FSC in daily caregiving. Conclusions: FSC is a dynamic, multidimensional process shaped by lived experience, family interactions, and systemic support. The findings support inclusive, family-centered care models and inform clinical practice, training, and policy in pediatric IDs. Full article

Objectives/Background: Aarskog–Scott syndrome (AAS), also known as faciogenital dysplasia, is a rare X-linked genetic disorder primarily characterized by its diverse physical manifestations. Previous evidence suggests a potential association between AAS and neurodevelopmental disorders, including autism spectrum disorder (ASD). Methods: This case study presents a male adolescent with ASD and a novel genetic variant in FGD1 underlying AAS. We conducted comprehensive clinical, genetic, and behavioral assessments to characterize the neurodevelopmental presentation. Moreover, we examined the existing literature on AAS and comorbid neurodevelopmental disorders. Results: The patient demonstrated features consistent with both AAS and ASD, presenting with characteristic physical features of AAS and meeting diagnostic criteria for ASD on both ADI-R and ADOS-2. Cognitive assessment revealed above-average nonverbal IQ (Leiter-3, NVIQ = 115), while adaptive functioning was notably impaired (Vineland composite score = 65). Executive function deficits were identified through several assessments, though ADHD diagnostic criteria were not met. The literature review considered 64 studies, including 151 individuals with AAS. ASD was observed in 4.0%, Attention Deficit/Hyperactivity Disorder (ADHD) in 10.6%, and Intellectual Disability (ID) in 14.2% of cases. Conclusions: The combination of ASD with preserved nonverbal intelligence but impaired adaptive functioning in this AAS case demonstrates the complex neurodevelopmental manifestations possible in this rare genetic condition. The prevalence of neurodevelopmental disorders among people with AAS may be higher than their prevalence in the general population. However, a comprehensive assessment of developmental progress was rarely performed in previous studies, which may lead to systematic underestimation of co-occurring neurodevelopmental difficulties in AAS. Full article

Background/Objectives: Neurodevelopmental disorders (NDDs) represent a clinically diverse group of conditions that affect brain development, often leading to varying degrees of functional impairment. Many NDDs, particularly syndromic forms, are caused by genetic mutations affecting critical cellular pathways. Ribosomopathies, a subgroup of NDDs, are linked to defects in ribosomal function, including those involving the synthesis of diphthamide, a post-translational modification of translation elongation factor 2 (eEF2). Loss-of-function (LoF) mutations in genes involved in diphthamide biosynthesis, such as DPH1, DPH2, and DPH5, result in developmental delay (DD), intellectual disability (ID), and multisystemic abnormalities. DPH5-related diphthamide deficiency syndrome has recently been reported as an ultrarare disorder linked to LoF mutations in DPH5, encoding a methyltransferase required for diphthamide synthesis. Methods: Clinical, neurological, and dysmorphological evaluations were performed by a multidisciplinary team. Brain MRI was acquired on a 3T scanner. Craniofacial abnormalities were assessed using the GestaltMatcher phenotyping tool. Whole exome sequencing (WES) was conducted on leukocyte-derived DNA with a trio-based approach. Bioinformatic analyses included variant annotation, filtering, and pathogenicity prediction using established databases and tools. Results: The affected subject carried a previously reported missense change, p.His260Arg, suggesting the occurrence of genotype–phenotype correlations and a hypomorphic behavior of the variant, likely explaining the overall milder phenotype compared to the previously reported patients with DPH5-related diphthamide deficiency syndrome. Conclusions: Overall, the co-occurrence of short stature, relative macrocephaly, congenital heart defects, variable DD/ID, minor skeletal and ectodermal features, and consistent craniofacial features suggests a differential diagnosis with Noonan syndrome and related phenotypes. Full article

Background: Developmental delay and intellectual disability (DD/ID) are frequently accompanied by epilepsy, and growing evidence implicates variants in voltage-gated calcium channel genes in their pathogenesis. This study aimed to investigate the association of polymorphisms in CACNA1A, CACNA1C, and CACNA1H with DD/ID and epilepsy comorbidity in Korean children. Methods: We retrospectively analyzed 141 pediatric patients diagnosed with DD/ID who underwent whole-exome sequencing (WES) and were not found to have pathogenic monogenic variants. Nine single-nucleotide polymorphisms (SNPs) across CACNA1A, CACNA1C, and CACNA1H were selected based on functional annotation scores and prior literature. Genotype data were extracted from WES variant files, and allele and genotype frequencies were compared with control data from the gnomAD East Asian population and the Korean Reference Genome Database (KRGDB). Subgroup analyses were performed according to epilepsy comorbidity. Results: The CACNA1A rs16023 variant showed a significantly higher B allele frequency in DD/ID patients than in both control datasets and was also associated with epilepsy comorbidity. Genotype distribution analysis revealed that the BB genotype of rs16023 was more frequent in patients with epilepsy. Conclusions: The CACNA1A rs16023 variant may contribute to genetic susceptibility to DD/ID and epilepsy in Korean children, potentially through regulatory mechanisms. These findings support the relevance of calcium channel genes in neurodevelopmental disorders and highlight the importance of integrating functional annotation in variant prioritization. Full article

Over the past decade, a growing body of evidence has highlighted the positive impact of full and equal participation in sport on the quality of life (QoL) of people with intellectual disabilities (IDs). However, access to mainstream sports remains limited due to persistent barriers, which leads to low participation levels among people with IDs. In this context, the Mixed Ability (MA) model offers an innovative approach by promoting the inclusion of people with and without disabilities in the same mainstream teams, without classification processes or modifications to the rules of the sport. Therefore, this study aimed to explore the relationship between rugby MA and the QoL and the needs of players with IDs. Using a convergent mixed methods design, the quantitative aspect involved 46 participants aged 18–57, engaged in eight different rugby teams, while the qualitative component included a focus group with four ID players from a rugby team. The findings revealed a positive correlation between higher QoL and the duration of participation in mainstream sports among the participants. Furthermore, a positive trend was also observed among individuals with moderate and severe intellectual disabilities. Qualitatively, participants highlighted the model’s emphasis on inclusivity, familial bonds, enjoyment, community spirit, active engagement, and opportunities to experience new activities. The shift towards inclusion requires modifying the community so that every person has opportunities to lead a valuable, meaningful, and self-determined life. In this sense, the MA sports model emerges as a potent instrument for fostering inclusive communities and enhancing the QoL of people with IDs. Full article

Introduction: People with disabilities are characterized by suboptimal health and lower self-rating health. Their need for health care is greater, they often have a higher prevalence of health problems and they have more difficulty accessing health care. The aim of this study was to assess the health behaviors and health indicators of 12–18-year-old young people with intellectual disabilities and autism spectrum disorder, and to explore their school-related perceptions in the Northern Great Plain region of Hungary. Materials and Methods: A cross-sectional questionnaire survey was conducted with the participation of 185 young people. A custom questionnaire was used, based on the Health Behavior in School-aged Children (HBSC) survey, assessing eating habits, oral care, physical activity, mental well-being, and self-reported health status. The sample was categorized into three groups: the ID1 (Intellectual Disability level 1) group, encompassing young individuals with mild intellectual disability; the ID2 group, encompassing young people with moderate intellectual disability; and the ID+ASD group, encompassing young individuals affected by both intellectual disability and autism spectrum disorder. Results: Consumption of various food types was below optimal levels. Low intake of fruits and vegetables was common, with only 21.6% of the respondents consuming fruit daily and 23.8% consuming vegetables daily. ID1 group reported significantly higher rates of nervousness several times a week (17.8% vs. 5.6% and 6.9%, p < 0.001), sleep difficulties (28.8% vs. 7.4% and 15.5%, p = 0.032), and dizziness (9.6% vs. 1.9% and 3.4%, p = 0.022) compared to the other two groups. A third school-related factor, related to negative emotions, showed a near-significant difference (p = 0.064), suggesting that students with both autism spectrum disorder and intellectual disability perceive lower levels of acceptance from teachers. On school-free days, computer usage was significantly highest in the ID+ASD group; 50% of them used a computer for at least 4 h per day. Conclusions: To improve mental well-being among affected children, psychological support and the implementation of mental health programs are recommended. In addition to teaching stress management techniques and coping mechanisms, integrating relaxation techniques into comprehensive developmental programs—both individually and in groups—is advised. For teachers, it is recommended to acquire disability-specific communication strategies. Full article

Background: Participation in sports offers children with intellectual disabilities (IDs) crucial opportunities for development. However, they often face barriers to inclusion in school-based sports, especially in under-resourced areas. This study aimed to (1) assess the level of participation in school sports among learners with IDs, and (2) explore teachers’ perceptions of the benefits and barriers to such participation in special schools within the Vhembe District of South Africa. Methods: A qualitative, descriptive research design was employed. Face-to-face semi-structured interviews were conducted with 20 teachers from four special schools. Thematic analysis helped identify key themes and interpret responses. Results: All schools offered weekly sports activities, as required by the Department of Education. Teachers viewed sports as vital for social interaction, physical fitness, and psychological well-being. However, barriers such as insufficient adapted equipment, inadequate facilities, and limited family support hindered meaningful participation, particularly for learners with profound disabilities. Conclusions: School sports have the potential to transform the lives of learners with IDs, but systemic barriers restrict access. Increased investment in inclusive infrastructure, adaptive equipment, teacher training, and community awareness is essential to align policy with practice in special education. Full article

Genetic studies have identified numerous candidate genes for neurodevelopmental disorders associated with intellectual disability (ID) and autism spectrum disorders (ASD). Some genetic anomalies are very rare or challenging to detect, making it essential to validate the presence of gene mutations or copy number variations in additional patients with similar clinical phenotypes. Background/Objectives: Case reports play a crucial role in this process by validating rare variants in phenotypically matched patients, shedding light on novel candidate genes linked to these disorders. Methods: Patients with ID and ASD underwent neurological examinations, brain magnetic resonance imaging (MRI), sleep and wake electroencephalogram (EEG), neuropsychological evaluations, and laboratory tests including molecular analysis for fragile-X syndrome and array comparative genomic hybridization (aCGH). Results: We observed a patient with ID and ASD who carried a microdeletion in Xq22.1 that affects only exon 1 and intron 1 of the Nuclear RNA Export Factor 5 (NXF5) gene. The patient’s phenotypic features overlap with those of the only four previously reported cases of variations involving the same gene. Conclusions: Our findings suggest that NXF5 may play a role in neurodevelopmental disorders and should be considered in the spectrum of X-linked ID associated with ASD. Full article

This exploratory qualitative study investigates the challenges faced by young adults (aged 18–40) with severe mental illness (SMI), intellectual disabilities (IDs), and autism spectrum disorder (ASD) in navigating body perception, affectivity, intimacy, gender identity, and sexuality. Through semi-structured interviews with 13 participants recruited from a community habilitation center, thematic analysis revealed systemic barriers rooted in societal stigma, familial overprotection, and institutional neglect. Key findings highlight tensions between bodily autonomy and familial control, with prolonged caregiver dependency in intimate hygiene reflecting patterns of infantilization. We found that participants’ self-image was shaped by gendered expectations and familial critiques, reinforcing internalized stigma. Romantic relationships were often idealized through cultural narratives, yet lacked practical guidance on consent or boundaries, exacerbating vulnerabilities. Fragmented sexual education left individuals reliant on pornography or peers, perpetuating misconceptions and anxiety. Despite these barriers, participants demonstrated resilience and agency in advocating for inclusive interventions. This study underscores the urgent need for trauma-informed, rights-based approaches that prioritize autonomy, dignity, and intersectionality. Recommendations include structured skill-building programs for independence, disability-adapted comprehensive sexuality education, and systemic reforms fostering interdisciplinary collaboration. By centering lived experiences, this work challenges structural inequities and advocates for community care models that honor the diverse needs of individuals navigating the intersection of disability, identity, and sexuality. Full article

A key goal of inclusive education is to enhance health literacy skills, empowering students with intellectual disabilities (IDs) to access critical information needed to navigate everyday challenges. The COVID-19 pandemic, for example, highlighted unique barriers to preparedness for people with IDs regarding social behavior and decision-making. This study aimed to examine students’ awareness and understanding of pandemic outbreaks. Using an inquiry-based approach supported by Digital Learning Objects (DLOs), the research assessed students’ knowledge and perceptions of viruses, modes of transmission, and preventive measures. An in-depth visual analysis within a single-subject research design demonstrated that interdisciplinary educational scenarios on infectious diseases can be effective for students with ID, especially when DLOs are integrated with targeted instructional techniques. Full article