SEARCH · PubMed Health

Results for “Intellectual Disability”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed2026

Disruption of GAD1 protein architecture by a novel missense variant in a consanguineous family with autosomal recessive intellectual disability.

BACKGROUND: Intellectual disability represents a heterogeneous group of neurodevelopmental disorders marked by significant impairments in intellectual functioning and adaptive behavior. Among the various causes, genetic factors play a major role, with autosomal recessive intellectual disability (ARID) constituting a genetically diverse subgroup. ARID is prevalent in consanguineous families and arises from homozygous mutations that disrupt critical genes involved in brain development and function. OBJECTIVE: This study aimed to identify disease-causing genetic variants responsible for ARID in a consanguineous Pakistani family and to evaluate the structural and functional impact of a novel variant identified in GAD1 through protein modeling. METHODS: A consanguineous family affected with intellectual disability was enrolled. Whole-exome sequencing was performed on an affected individual, followed by bioinformatics analysis including alignment to the GRCh38 reference genome, variant calling, and annotation. Variants were filtered based on rarity, predicted functional impact, and autosomal recessive inheritance pattern. Candidate variants were validated and assessed by Sanger sequencing and segregation analysis. Protein modeling was performed to evaluate the structural impact of the identified variant. RESULTS: A novel homozygous missense variant NM_000817:c.1700G>A;p.Arg567Gln in GAD1 was identified. Segregation analysis confirmed co-segregation of the variant with the affected phenotype. Protein modeling suggested that the variant may disrupt GAD1 enzymatic function involved in gamma-aminobutyric acid synthesis. CONCLUSION: This study emphasizes the significance of genetic investigation in familial cases and the crucial role that GAD1 mutations play in neurodevelopmental disorders with intellectual disability. The results advance the knowledge of molecular causes of ARID and broaden the mutational range.

Pakistani↗

PubMed2025

Identification of intragenic variants in pediatric patients with intellectual disability in Peru.

BACKGROUND: Intellectual disability in Latin America can reach a frequency of 12% of the population, these may include nutritional deficiencies, exposure to toxic or infectious agents, and the lack of universal neonatal screening programs. In 90% of patients with intellectual disability, the etiology can be attributed to variants in the genome. OBJECTIVE: to determine intragenic variants in patients with intellectual disability between 5 and 18 years old at Instituto Nacional de Salud del Niño. METHODS: It is a descriptive cross-sectional study with convenience sampling. A total of 124 children diagnosed with intellectual disability were selected based on psychological test results and availability for whole exome sequencing. In addition, a chromosomal analysis of 6.55 M was performed on ten patients with a negative result in sequencing. Relative and absolute frequencies and measures of central tendency and dispersion were determined according to their nature. In addition, multiple linear regression and Poisson regression were used to determine the association between some clinical characteristics and the probability of occurrence in patients with positive results. RESULTS: The median age of the patients was 6.3 (IQR = 5.95), males accounted for 57.3%, and 91.9% of the cases had mild intellectual disability. Exome sequencing determined the etiology in 30.6% of patients with intellectual disability, of which 52.6% were autosomal dominant inheritance. The most frequent genes found were MECP2, STXBP1 and LAMA2. A broad genotype-phenotype correlation was identified, highlighting the genetic heterogeneity of intellectual disability in this population. The presence of dermatologic lesions, dystonia, peripheral neurological disorders, and fourth finger flexion limitation were observed more frequently in patients with intellectual disability with "positive results". CONCLUSIONS: This study shows that one-third of patients with intellectual disability exhibit intragenic variants, highlighting the importance of genetic analysis for accurate diagnosis. The identification of genes such as MECP2, STXBP1, and LAMA2 underscores the genetic heterogeneity of intellectual disability in the studied population. These findings emphasize the need for genetic testing in clinical management and the implementation of early detection programs in Peru.

Humans↗

PubMed2025

"All doctors should be trained in that": The coproduction and mixed-methods evaluation of an educational toolkit to enable safe, high-quality genetic health care for people with intellectual disability.

PURPOSE: People with intellectual disability inequitably access high-quality genetic health care. However, they are keen to understand genetic health care and recommend that clinicians need education on delivering more inclusive care and that multimodal genetic health literacy resources should be coproduced. METHODS: Our inclusive research team applied best-practice coproduction principles to deliver a suite of resources, the GeneEQUAL Toolkit. Mixed-methods evaluation, including surveys and focus group/interviews, assessed (1) clinicians' perceived capabilities, motivation, and opportunities for providing inclusive health care for people with intellectual disability before and after exploring the Toolkit; (2) the perceptions and opinions of people with intellectual disability about the Toolkit; (3) the reach of the Toolkit components; and (4) the reflections of people with intellectual disability and clinicians on the coproduction process. RESULTS: The Toolkit met the expectations and preferences of people with intellectual disability and clinicians, and had a global reach. Coproduction was feasible and judged as critical for the high value of the Toolkit, in motivating clinicians to change their clinical practice and empowering people with intellectual disability. CONCLUSION: Coproduction can be successfully applied to improve the engagement of people with intellectual disability, potentially reducing health inequity and improving the safety and quality of genetic health care.

Humans↗

PubMed1992

Generalized effects of a peer-delivered first aid program for students with moderate intellectual disabilities.

Peers with mild intellectual disabilities taught first aid skills to 4 students with moderate intellectual disabilities. A multiple probe design across participants was used to examine the effects of the peer teaching program during an acquisition and a partial sequential withdrawal phase. Generalization assessments were conducted in the participants' homes using novel, randomized simulated injuries. Results suggested that the peer teaching program resulted in acquisition of first aid skills, and the participants' skills generalized to the home, to novel simulated-injury locations, and to new trainers. Additionally, a more detailed analysis of the generalized responding suggested that when given a choice among first aid materials, participants treated burns using large adhesive bandages rather than the materials used in training. Participants also successfully treated injuries when novel instructional cues were used. The findings are discussed with respect to training issues, generalization and maintenance of the acquired skills, and the use of peer tutors with disabilities.

Child↗

PubMed2024

Variants in HCFC1 and MN1 genes causing intellectual disability in two Pakistani families.

BACKGROUND: Intellectual disability (ID) is a neurodevelopmental condition affecting around 2% of children and young adults worldwide, characterized by deficits in intellectual functioning and adaptive behavior. Genetic factors contribute to the development of ID phenotypes, including mutations and structural changes in chromosomes. Pathogenic variants in the HCFC1 gene cause X-linked mental retardation syndrome, also known as Siderius type X-linked mental retardation. The MN1 gene is necessary for palate development, and mutations in this gene result in a genetic condition called CEBALID syndrome. METHODS: Exome sequencing was used to identify the disease-causing variants in two affected families, A and B, from various regions of Pakistan. Affected individuals in these two families presented ID, developmental delay, and behavioral abnormalities. The validation and co-segregation analysis of the filtered variant was carried out using Sanger sequencing. RESULTS: In an X-linked family A, a novel hemizygous missense variant (c.5705G > A; p.Ser1902Asn) in the HCFC1 gene (NM_005334.3) was identified, while in family B exome sequencing revealed a heterozygous nonsense variant (c.3680 G > A; p. Trp1227Ter) in exon-1 of the MN1 gene (NM_032581.4). Sanger sequencing confirmed the segregation of these variants with ID in each family. CONCLUSIONS: The investigation of two Pakistani families revealed pathogenic genetic variants in the HCFC1 and MN1 genes, which cause ID and expand the mutational spectrum of these genes.

Humans↗

PubMed1992

Seizures and intellectual disability associated with tuberous sclerosis complex in the west of Scotland.

Of 104 individuals with tuberous sclerosis complex ascertained from the total population of the west of Scotland, 52 were born before and 52 after 1st July 1966. Of those born before. 10 had no seizures, 14 had seizures and no intellectual disability and 28 had seizures and intellectual disability; of those born after, four had no seizures, 18 had seizures and 30 had seizures and a degree of intellectual disability. Infantile spasms or other generalised seizures as the presenting seizure type (N = 29) was strongly associated with intellectual disability; partial seizures as the presenting seizure type (N = 19) was associated with normal development. Although the onset of seizures under one year of age and the presence of multiple seizure types were associated with intellectual disability, the strongest association was with the type of presenting seizure.

Child↗

PubMed2026

What Constitutes Effective Support and Provision Within Day Service Centres for People With Intellectual Disabilities? A Systematic Review of Qualitative Research.

BACKGROUND: This review aimed to investigate the effectiveness and quality of support and provision within day service centres for people with intellectual disabilities. METHOD: The International Bibliography of the Social Sciences, Scopus and PsycInfo databases were searched in August 2024, and the results were reported according to the PRISMA guidelines. Peer-reviewed, English-language, qualitative studies that investigated the effectiveness of day service provision for people with intellectual disabilities in non-residential settings were considered for review. Methodological quality of the included studies was assessed using the JBI Critical Appraisal Tool for qualitative research. Qualitative themes were identified through thematic analysis and synthesised using the ConQual approach. RESULTS: Fourteen studies were included and four key themes emerged: 'perceptions of service quality'; 'community-orientation, integration, and empowerment'; 'challenging behaviours and safety'; and 'staff-centred factors and job satisfaction'. Confidence in the evidence was 'very low' for 3/4 themes, while there was 'moderate' confidence in the evidence related to the theme 'perceptions of service quality'. CONCLUSIONS: Day service centres for people with intellectual disabilities may enhance their effectiveness and quality of provision by concentrating on promoting communication, engagement, relationships, social networks and community integration. Addressing the methodological shortcomings and incomplete reporting of related research in future would contribute to improvements in overall confidence in the evidence base. This can then be better used to inform and further enhance day service provision for people with intellectual disabilities.

Humans↗

PubMed1991

The aetiology of intellectual disability in Western Australia: a community-based study.

A register of intellectual disability is being established to assess the level and aetiology of intellectual disability in all children born and/or living in Western Australia. 1602 children aged between six and 16 years were identified who had IQs less than 70. 40 per cent had a definite genetic basis, 20 per cent an environmental cause and 40 per cent were of unknown aetiology. The insult was prenatal in 61 per cent, 10 per cent had a possible perinatal cause, 8 per cent were postnatal and for 21 per cent the timing could not be assessed. Approximately 20 per cent had concomitant cerebral palsy and 13 per cent were epileptic. A disparity was found between rural and urban areas, the prevalence being 9.9 and 6.5 per 1000 live births.

Adolescent↗

PubMed2025

Guidelines for the Creation of Accessible Consent Materials and Procedures: Lessons from Research with Autistic People and People with Intellectual Disability.

Informed, voluntary, ongoing consent is a central tenet of ethical research. However, consent processes are prone to exclusionary practices and inaccessibility. Consent materials are often too long and complex to foster understanding and ensure that people make truly informed decisions to participate in research. While this complexity is problematic for all people, these challenges are compounded for autistic people and people with intellectual disability. Consent materials and procedures rarely incorporate accommodations for processing and communication differences common in autism and intellectual disability. Failure to provide such accommodations ultimately threatens the conduct of ethical research. We describe lessons learned across multiple major U.S. research institutions that improved informed consent materials and procedures, with the goal of fostering responsible inclusion in research for autistic people and people with intellectual disability. We used these alternative materials and procedures in multiple research projects with samples of autistic people and people with intellectual disability. Each contributing team partnered with university human research participant protections personnel, accessibility experts, community members, and researchers to develop rigorous procedures for improving the readability and accessibility of informed consent materials. We present guidelines for designing consent materials and procedures and assert that participatory methods are vital to the success of ongoing accessibility initiatives. Adoption of understandable consent materials and accessible consent procedures can cultivate more equitable, respectful, and inclusive human research practices. Future work should expand on this work to design inclusive practices for populations with additional considerations.

autism↗

PubMed1992

The right to procreate: intellectual disability and the law.

The common law recognizes the right of every woman to bear a child and will not contravene that right unless there are compelling reasons for doing so. The issue of the right of intellectually disabled girls, below the age of 18 years, to ultimately bear a child has now been removed to the courts. Following a recent High Court decision, surgery resulting in the sterilisation of intellectually disabled minors cannot be performed without the sanction of the Family Court. Intellectually disabled women differ in that they are legally adults once they reach the age of majority with presumed full adult rights to consent to medical treatment. Other legal mechanisms are require when they lack this capacity. This article discusses the High Court case and others that have been heard in Australia recently.

Adolescent↗

PubMed1992

Demographic characteristics of a population of people with moderate, severe and profound intellectual disability (mental handicap) over 50 years of age: age structure, IQ and adaptive skills.

Studies characterizing community populations of older people with intellectual disability (mental handicap) have frequently derived data from mental handicap registers. Such large-scale studies permit the establishment of reliable age trends, yet may utilize unreliable information and omit some individuals. Here, a functional characterization of a 50+ years sample with moderate, severe and profound intellectual disability is described, in which an extensive outreach exercise to identify individuals not known to mental handicap service providers ensured that almost 100% of people fulfilling the residence, age and ability criteria were included. Functional level, assessed by the Adaptive Behaviour Scale (ABS), is reported in relation to six factors derived from factor analysis. Overall, the sample was relatively high functioning and generally free of severe problem behaviours. There was no evidence for significant age-related functional decline.

Activities of Daily Living↗

PubMed1992

Increases in knowledge following a course of sex education for people with intellectual disabilities.

Although sex education programmes are thought to be useful in teaching people with intellectual disabilities, there is very little evidence that the material taught is retained by clients. This paper reports data which has been collected routinely on a sex education programme. Forty-six subjects were assessed on their level of sexual knowledge in seven areas: parts of the body, masturbation, male puberty, female puberty, intercourse, pregnancy and childbirth, and birth control and venereal disease. They were retested after a 9-month sex education programme and tested again at a 3-month follow-up. A control group of 14 subjects were tested on two occasions, 4 months apart. There were significant and substantial increases in sexual knowledge on all areas for the experimental group. The control group showed no corresponding increases in knowledge.

Adolescent↗

PubMed2026

Identification of novel HUWE1 variants in Turner-type X-linked intellectual disability.

OBJECTIVE: To characterize the clinical phenotypes and identify the genetic etiology in four unrelated families affected by Turner-type X-linked intellectual disability (XLID). METHODS: Peripheral blood samples were collected from four probands and their parents. Genomic DNA was extracted, and a comprehensive genetic analysis was performed using trio-based Whole Exome Sequencing (WES) combined with low-pass Copy Number Variation sequencing (CNV-seq). Candidate variants were subsequently validated via Sanger sequencing. RESULTS: Genetic analysis identified distinct variants in the HUWE1 across the four families. Specifically, four distinct HUWE1 variants were identified across the families: a hemizygous c.10034 > T (p.Lys3345Met) in Family 1; a heterozygous c.9209G > A (p.Arg3070His) in Family 2; a heterozygous c.12688T > C (p.Phe4230Leu) in Family 3; and a hemizygous c.9070G > A (p.Ala3024Thr) in Family 4. In accordance with ACMG guidelines, the novel variants in Families 1, 3, and 4 were classified as "Likely Pathogenic" (PS2 + PM2_Supporting + PP2 + PP3). In contrast, the previously reported variant in Family 2 was categorized as "Pathogenic" based on the criteria PS2 + PM2_Supporting + PM5 + PP2 + PP3_Moderate. All probands were clinically diagnosed with Turner-type XLID. CONCLUSIONS: This study expands the pathogenic variant spectrum of HUWE1 and provides novel molecular evidence for the clinical diagnosis of Turner-type XLID. These findings are of significant value for genetic counseling, carrier screening, and prenatal diagnosis for the affected families.

Humans↗

PubMed1992

The administration of psychotropic and anticonvulsant drugs to children with profound intellectual disability and multiple impairments.

A national (England and Wales) postal survey of families with a son or daughter with profound intellectual disability and multiple physical and sensory impairments who lived at home was undertaken. A section of the questionnaire dealt with prescription of major tranquillizers, drugs with a sedative function, anticonvulsants and stimulants, while among other variables information was also collected on sex, age, behaviour problems, sleep difficulties and epilepsy. Of children and adults: 5.3 and 7.9%, respectively, were receiving major tranquillizers; 28.5 and 24.5%, respectively, were prescribed drugs with a sedative function; and 53.4 and 52.7% were in receipt of anticonvulsants, with no individuals in receipt of stimulants. Only 1.5% of the total sample received major tranquillizers, drugs with a sedative function and anticonvulsants, though 18.9% were prescribed drugs from two classes, notably drugs with a sedative function and anticonvulsants. In all, 66.3% of the combined child and adult samples received at least one drug from the classes investigated. No sex bias in prescribing was found. Receipt of major tranquillizers bore some relation to reported behaviour problems, while administration of sedatives and anticonvulsants were related respectively to reports of sleep problems and occurrence of epilepsy.

Adolescent↗

PubMed2026

Identification of biallelic loss-of-function PREP variants in three individuals with syndromic intellectual disability.

BACKGROUND: Neurodevelopmental disorders are one of the most prevalent reasons for genetic testing in childhood. Despite the identification of over 1950 associated genes, many proposed candidate genes lack convincing gene-disease validity. The gene PREP encodes the broadly expressed prolyl endopeptidase whose exact function remains largely unknown. A homozygous PREP variant has been reported once as a candidate gene in two siblings with intellectual disability but no functional studies were conducted. METHODS: Exome and trio genome sequencing were performed in two unrelated families as part of larger cohorts. Segregation analysis, RNA sequencing and immunoblots were performed to further examine the pathogenicity of detected PREP variants. RESULTS: We report three individuals from two unrelated families who presented with intellectual disability, behavioural abnormalities, strabismus, generalised muscular hypotonia, dysmorphic facial features and epilepsy. Exome and genome sequencing identified two different homozygous rare PREP variants: c.1570_1573dup, p.(Asn525Thrfs*5) and c.1839-2A>G, p.?. RNA sequencing confirmed the detected intronic variant to result in two aberrant mRNA isoforms. In patient-derived cells immunoblots showed absence of PREP protein. CONCLUSION: Our data suggest PREP deficiency as the underlying cause of a syndromic neurodevelopmental disorder.

Female↗

PubMed1992

Appraised significance of intellectual disability for parents of children in three age cohorts: exploring the stress process.

The conceptualization of stress as a process involving stressors, mediators and manifestations of stress has opened up a way of more systematically investigating the impact of perceptions on stress experienced by parents of children with intellectual disabilities. Results obtained at the end of the first part of a two-stage panel design study indicate that appraised significance perceptions of parents are potentially exacerbating mediators of parental stress. Findings of a multiple regression analysis were interpreted as being consistent with the proposition that the parent-appraised significance of the child's disability for their parental role becomes increasingly salient as an exacerbating mediator of parental stress during the later childhood to early adolescent years. An attempt will be made to test this proposition when the children in the 3-5 year old cohort moves into the 10-12 year-old age category.

Activities of Daily Living↗

PubMed2026

Intellectual disability, neuroregression and adult-onset progressive dystonia due to a DLG4 pathogenic variant.

We report a 34-year-old male with childhood developmental delay, severe intellectual disability in adulthood, episodes of agitation with a previous diagnosis of schizoaffective disorder and adult-onset cognitive regression who developed progressive generalised dystonia due to a de novo DLG4 pathogenic loss-of-function variant. This case expands the phenotypic spectrum of recognised movement disorder manifestations associated with DLG4-related synaptopathy.

Humans↗

PubMed2025

Deleterious, protein-altering variants in GSPT2 are putatively associated with an X-linked neurodevelopmental disorder with intellectual disability, language impairment, autism, and epilepsy.

PURPOSE: Approximately 6% of individuals with neurodevelopmental disorders are predicted to be X-linked, and the GSPT2 gene, located at Xp11.22, has not yet been associated with any Mendelian disease. METHODS: To establish genotype-phenotype associations between GSPT2 and neurodevelopmental disorders, clinical investigations were performed in unrelated individuals, genomic and functional studies were conducted on the participants' blood and heterologous cell system. RESULTS: We described 6 individuals from 6 unrelated families carrying hemizygous variants in GSPT2 with intellectual disability, delayed speech and language development, autism spectrum disorder, epilepsy, or abnormal fetal neurodevelopment. Structural molecular modeling revealed significant deleterious effects of the identified variants. GSPT2 is preferentially enriched in the brain and cerebellum compared with other tissues. GSPT2-deficient H4 neuroglioma cells slow down the proliferation and downregulate the expression of cell-cycle-related genes. Transcriptomics revealed that GABAergic and calcium-signaling-related genes were significantly downregulated in GSPT2-deficient cells. Consistent with the transcriptomic data, RT-PCR analysis verified the marked downregulation of critical genes (CACNA1B, etc) in GSPT2-knockout cells and further confirmed these findings with proteomic profiling. CONCLUSION: Our data suggest a putative GSPT2-related X-linked neurodevelopmental disorders through dysregulation of cell-cycle progression and calcium/GABAergic signaling pathways.

Humans↗