Intellectual Disability Research Articles

Exploring the views and experiences of professionals using PBS and emotional development assessment for individuals with an intellectual disability: a case study

Purpose The purpose of this paper was to investigate the utility of including emotional development (ED) assessment into a Positive Behaviour Support (PBS) approach in clinical practice with a patient with an intellectual disability (ID) and challenging behaviour. Design/methodology/approach Interviews were conducted with four staff involved in the care of the patient. The interviews were transcribed and analysed using thematic analysis and three reflective sessions were completed with the lead psychologist of the service. Findings Using thematic analysis, four themes were identified: getting everyone around the table: a collaborative approach, complementary approaches: a feedback loop, helping to make sense of the individual and ensuring a voice for service users. Research limitations/implications This was a case study selected from routine clinical practice and as such generalisability may be limited. This case study was designed as an exploration of the potential benefits of incorporating ED alongside PBS for ID and provides a basis for future research. Practical implications This study highlights the value of integration of ED assessment for people with ID and challenging behaviour within a healthcare team. Originality/value There is a lack of literature relating to ED and challenging behaviour within an ID population, particularly exploring ED within a PBS framework. This study provides a starting point for exploring how practice can be improved through incorporating ED assessment for individuals with ID and challenging behaviour.

Cyclin‐dependent kinase 13 is indispensable for normal mouse heart development

AbstractCongenital heart disease (CHD) has an incidence of approximately 1%. Over the last decade, sequencing studies including large cohorts of individuals with CHD have begun to unravel the genetic mechanisms underpinning CHD. This includes the identification of variants in cyclin‐dependent kinase 13 (CDK13), in individuals with syndromic CHD. CDK13 encodes a serine/threonine protein kinase. The cyclin partner of CDK13 is cyclin K; this complex is thought to be important in transcription and RNA processing. Pathogenic variants in CDK13 cause CDK13‐related disorder in humans, characterised by intellectual disability and developmental delay, recognisable facial features, feeding difficulties and structural brain defects, with 35% of individuals having CHD. To obtain a greater understanding for the role that this essential protein kinase plays in embryonic heart development, we have analysed a presumed loss of function Cdk13 transgenic mouse model (Cdk13tm1b). The homozygous mutants were embryonically lethal in most cases by E15.5. X‐gal staining showed Cdk13 expression localised to developing facial regions, heart and surrounding areas at E10.5, whereas at E12.5, it was more widely present. In the E15.5 heart, staining was seen throughout. RT‐qPCR showed significant reduction in Cdk13 transcript expression in homozygous compared with WT and heterozygous hearts at E10.5 and E12.5. Detailed morphological 3D analysis of embryonic and postnatal hearts was performed using high‐resolution episcopic microscopy, which affords a more detailed analysis of structures such as cardiac valve leaflets and endocardial cushions, compared with more traditional histological techniques. We show that both the homozygous and heterozygous Cdk13tm1b mutants exhibit a range of CHD, including ventricular septal defects, bicuspid aortic valve, double outlet right ventricle and atrioventricular septal defects. 100% (n = 4) of homozygous hearts displayed CHD. Differential expression was seen in Cdk13tm1b homozygous mutants for two genes known to be necessary for normal heart development. The types of defects, and the presence of CHD in heterozygous mice (17.02%, n = 8/47), are consistent with the CDK13‐related disorder phenotype in humans. This study provides important insights into the effects of reduced function of CDK13 in the mouse heart and contributes to our understanding of the mechanism behind this disorder as a cause of CHD.

Adapting the Tree of Life group for adults with intellectual disabilities: a feasibility and acceptability study

Adapting the Tree of Life group for adults with intellectual disabilities: a feasibility and acceptability study

Oral health status of children with intellectual and developmental disabilities in India: a systematic review and meta-analysis

Oral health status of children with intellectual and developmental disabilities in India: a systematic review and meta-analysis

Prenatal ozone exposure and risk of intellectual disability

Prenatal ozone exposure and risk of intellectual disability

A novel USP51 variant in a patient with autism spectrum disorder and epilepsy

Abstract Background Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder characterized by impaired social communication and repetitive behaviours. The genetic basis of ASD is complex and involves both rare variants with large effect sizes and common variants with small effect sizes. Case presentation This case report describes a 19-year-old male with ASD, intellectual disability, absent speech, and epilepsy. Molecular testing revealed a novel maternally inherited variant in the USP51 gene, which encodes Ubiquitin Specific Peptidase 51, a deubiquitinating enzyme involved in the DNA damage response. Conclusions Based on current knowledge, the variant is predicted to result in a truncated protein and is considered a variant of uncertain significance (VUS). The USP51 gene has been implicated in neurodevelopment, and its role in the developing brain suggests its potential relevance to ASD. Further studies are needed to establish the association of USP51 variants with ASD and elucidate the full phenotypic spectrum associated with these variants.

Loss of tissue-type plasminogen activator causes multiple developmental anomalies

Abstract Hydrocephalus and Dandy-Walker malformation are among the most common congenital brain anomalies. We identified three consanguineous families with both obstructive hydrocephalus and Dandy-Walker malformation. To understand the molecular basis of these anomalies, we conducted genome-wide sequencing in these families. We identified three homozygous truncating variants in the PLAT gene in the four affected family members. All of them showed tetraventricular hydrocephalus. In two individuals, a membrane at the inferior aspect of the fourth ventricle was likely the cause of their hydrocephalus. Three cases exhibited Dandy-Walker malformation whereas the two oldest individuals displayed intellectual disability. PLAT encodes the tissue-type plasminogen activator, a serine protease whose main function is to cleave the proenzyme plasminogen to produce active plasmin. Interestingly, plasminogen deficiency has also been shown to cause obstructive hydrocephalus and Dandy-Walker malformation, suggesting that loss of PLAT causes these defects by disrupting plasmin production. In summary, we describe a recessive disorder characterized by obstructive hydrocephalus, Dandy-Walker malformation and intellectual disability in individuals with loss-of-function variants in PLAT. This discovery further strengthens the involvement of the plasminogen pathway in the pathogenesis of these developmental disorders.

Altered expression of Csnk1a1p in Autism Spectrum Disorder in Iranian population: case-control study.

Over the past decade, substantial scientific evidence has showed that long non-coding RNAs (lncRNAs) are extensively expressed and play a crucial role in gene modulation through a diverse range of transcriptional, and post-transcriptional mechanisms. Recent discoveries have emphasized the involvement of lncRNAs in maintaining cellular homeostasis and neurogenesis in the brain. Accumulating reports identified dysregulated lncRNAs associated with psychiatric disorders, including autism. In this study, we examined the expression levels of DISC2, Linc00945, Foxg1-as1, Csnk1a1p, and Evf2 lncRNAs in blood samples from 21 clinically diagnosed autistic patients based on the Diagnostic and Statistical Manual of Mental Disorders criteria-5th edition (DSM-5), compared to age, sex, and ethnically-matched 25 healthy individuals. RNA extraction and cDNA synthesis were performed, followed by real-time PCR for quantification of lncRNAs expression levels. Receiver operating characteristic (ROC) curve analysis was used to evaluate biomarker potential. Additionally, we investigated the correlation between gene expression levels and autism comorbidities. Our results showed a significant decrease in Csnk1a1p expression in patients with autism spectrum disorder (ASD) compared to healthy children (P value = 0.0008). ROC curve analysis indicated that Csnk1a1p expression levels could effectively discriminate patients from healthy controls (AUC = 0.837, P value = 0.000284). No significant differences were observed between Csnk1a1p expression levels and comorbidity with ADHD or intellectual disability (p-value > 0.05). Based on these findings, Csnk1a1p may play a significant role in autistic patients and could serve as a potential biomarker for diagnostic and predictive purposes, as well as a therapeutic target.

Exploring the Strengths and Resilience of Siblings of People With Intellectual and Developmental Disabilities.

Siblings play a crucial role in shaping and guiding the experiences of their brother or sister with a disability across the lifespan. However, little is known about the positive outcomes of their roles and experiences as siblings. Understanding the positive outcomes challenges stereotypes and the stigma associated with disabilities and allows for a more holistic view of sibling experiences. We conducted a survey with 140 adult siblings of people with disabilities to explore their strengths, resilience and community belonging. We found that siblings highly rated their perceived strengths across various domains. Furthermore, siblings maintained high levels of resilience and most belonged to various organisations for social support. We also noted several strengths-based factors that predicted siblings' resilience. Our findings offer significant insights into siblings' inherent and developed strengths and the role of community networks in promoting sibling resilience and expanding their support systems.

Exploring 17q12 Deletion Syndrome: A Case Report of Neurodevelopmental, Endocrine, and Genital Anomalies

Objective − 17q12 deletion syndrome is a rare genetic disease characterized by neurodevelopmental disorders, genital and renal abnormalities, and maturity-onset diabetes of the young type 5 (MODY5).Case Report − This case report details the case of a 13-year-old female with moderate intellectual disability, Mayer-Rokitansky-Küster-Hauser syndrome, multicystic dysplastic kidneys, and MODY5. Genetic testing revealed a 1.52-megabase heterozygous deletion on chromosome 17q12, encompassing the HNF1B and LHX1 genes, which was found to be inherited from the mother. Conclusion − This case underscores the importance of early genetic testing and multidisciplinary approach in managing the multisystemic manifestations of 17q12 deletion syndrome. Early diagnosis and appropriate management are crucial for improving the outcomes and quality of life for affected individuals.

Transitioning to Adult Life for Students With Intellectual Disability in Saudi Arabia: A Systematic Literature Review

Although transition services for individuals with intellectual disability (ID) in Saudi Arabia are required by special education law and regulations, no literature synthesizes peer-reviewed studies focused on transition services for individuals with ID in Saudi Arabia. The purpose of this systematic literature review was to describe the peer-reviewed studies that have been published in English and Arabic over the past 15 years (2008–2023) related to transition services for individuals with ID in Saudi Arabia, the period in which the Saudi Arabian government has provided a new focus on the needs of individuals with disabilities. Our search yielded 22 studies that met the inclusion criteria for this systematic review. Results were discussed in terms of the lack of research focused on transition services and the lack of transition services available for individuals with ID in Saudi Arabia. A discussion of the limitations of this study, as well as the implications for future research, are provided.

Antiseizure medication use during pregnancy and children's neurodevelopmental outcomes.

The teratogenic potential of valproate in pregnancy is well established; however, evidence regarding the long-term safety of other antiseizure medications (ASMs) during pregnancy remains limited. Using routinely collected primary care data from the UK and nationwide Swedish registries to create a cohort of 3,182,773 children, of which 17,495 were exposed to ASMs in pregnancy, we show that those exposed to valproate were more likely to receive a diagnosis of autism, intellectual disability, and ADHD, when compared to children not exposed to ASMs. Additionally, children exposed to topiramate were 2.5 times more likely to be diagnosed with intellectual disability (95% CI: 1.23-4.98), and those exposed to carbamazepine were 1.25 times more likely to be diagnosed with autism (95% CI: 1.05-1.48) and 1.30 times more likely to be diagnosed with intellectual disability (95% CI: 1.01-1.69). There was little evidence that children exposed to lamotrigine in pregnancy were more likely to receive neurodevelopmental diagnoses. While further research is needed, these findings may support considering safer treatment alternatives well before conception when clinically appropriate.

ErbB inhibition rescues nigral dopamine neuron hyperactivity and repetitive behaviors in a mouse model of fragile X syndrome.

Repetitive stereotyped behaviors are core symptoms of autism spectrum disorders (ASD) and fragile X syndrome (FXS), the prevalent genetic cause of intellectual disability and autism. The nigrostriatal dopamine (DA) circuit rules movement and creation of habits and sequential behaviors; therefore, its dysregulation could promote autistic repetitive behaviors. Nevertheless, inspection of substantia nigra pars compacta (SNpc) DA neurons in ASD models has been overlooked and specific evidence of their altered activity in ASD and FXS is absent. Here, we show that hyperactivity of SNpc DA neurons is an early feature of FXS. The underlying mechanism relies on an interplay between metabotropic glutamate receptor 1 (mGluR1) and ErbB tyrosine kinases, receptors for the neurotrophic and differentiation factors known as neuregulins. Up-regulation of ErbB4 and ErbB2 in nigral DA neurons drives neuronal hyperactivity and repetitive behaviors of the FXS mouse, concurrently rescued by ErbB inhibition. In conclusion, beyond providing the first evidence that nigral DA neuron hyperactivity is a signature of FXS and nigral mGluR1 and ErbB4/2 play a relevant role in FXS etiology, we demonstrate that inhibiting ErbB is a valuable pharmacological approach to attenuate stereotyped repetitive behaviors, thus opening an avenue toward innovative therapies for ASD and FXS treatment.

Expanding diversity within phenylketonuria in ecuadorian patients: genetic analysis and literature review of newborn screenings.

Phenylketonuria (PKU) is an autosomal recessive metabolic disorder caused by a deficiency in the phenylalanine hydroxylase (PAH) enzyme, leading to the accumulation of phenylalanine and its metabolites, which are toxic to the central nervous system. Without treatment, PKU can result in severe intellectual disability and neurological issues. This study aims to present the first cohort of clinically described Ecuadorian PKU patients, analyzing genotype-phenotype correlations and comparing these variants with global databases to improve diagnosis and treatment in Ecuador. Detailed clinical histories were collected, and an analysis of genotype versus phenotype (affected protein domain) of the variant was performed. Among the PAH genotypes identified, we found 15 distinct variants, with c.[754C > T](p.Arg252Trp); [754C > T](p.Arg252Trp) being the most frequent genotype (23.68%), followed by c.[1045T > C](p.Ser349Pro); [1045T > C](p.Ser349Pro) (15.79%) and c.[441 + 5G > T]; [754C > T](p.Arg252Trp) (13.16%). Additionally, several unique genotypes were identified, such as c.[140G > A](p.Ala47Val); [140G > A](p.Ala47Val) and c.[331C > T](p.Arg111Ter); [1243G > A](p.Asp415Asn), which are not commonly reported in other populations. Most genotypes were heterozygous (63.2%). The majority of variants were missense variants (66.6%) affecting the catalytic domain (53.3%). The highest phenylalanine levels were found in patients with c.[754C > T](p.Arg252Trp); [754C > T] (p.Arg252Trp) (2700 umol/L). Phenotypic data were available for 11 patients, showing 45.45% with classic PKU, 45.45% with mild hyperphenylalaninemia, and 9% with mild PKU. There was a 63.6% concordance with the BIOPKU database. Five low-frequency genotypes not reported in BIOPKU were identified, suggesting unique regional variants. Our study highlights the genetic complexity of PKU in Ecuador, with a high prevalence of unique variants not commonly found in other regions. This underscores the necessity for region-specific genetic analysis to improve PKU diagnosis and treatment. The findings emphasize the importance of tailored therapeutic strategies and continued research to enhance outcomes for PKU patients in Latin America.

Theorizing the Role of Sex Educators in the Resistance and Reification of Epistemic Injustices Related to the Sexual Expression of People with Intellectual Disability.

People with intellectual disability face a variety of epistemic injustices-systems of knowledge and educational inequality-related to their access to sex education and perceptions of their sexuality. Sex educators are in a position to address these injustices; however, they may not be fully aware of their own epistemic ethics. Furthermore, there is little theoretical understanding of how sex educators provide instruction within an environment that exhibits hostility toward the sexual expression of those with intellectual disability. This grounded theory study of interviews with 58 people who taught sex education to people with intellectual disability sought to understand the role of educators in perpetuating and resisting epistemic injustice by utilizing sex education to either facilitate or restrict the sexual expression of people with disabilities. We identified four micro-contexts: centralizing capacity to consent, emphasizing risk, desexualizing (through) sex education, and acknowledging gender identity. In each micro-context, we explore mechanisms of how educators were either allied in support of autonomy (person-centered values, expertise, access to curricular resources, self-advocates as teachers and partners, subversiveness, and de-problematizing normative sexual behavior) or reified sexual stigmas (fear of sexual abuse and sexual perpetration, conscripting to asexuality, the paternalistic service system, and complex ethical dilemmas) in the context of hostility to sex education and sexual expression. These findings have implications for promoting prosocial sexual expression and access to sex education for people with intellectual disability.

Pineal gland volume in children with intellectual disability.

Pineal gland volume (PGV), which is associated with sleep and circadian rhythm, is known to be changed in some psychiatric disorders such as major depression, mood disorders and schizophrenia. This study aimed to compare the PGV of children with mild and moderate intellectual disability (ID) and healthy children. This multicentre retrospective study included 40 children with ID (patient group), aged 6-12 years and 40 age- and sex-matched healthy children (control group). The children were examined for their sociodemographic characteristics and for PGV using magnetic resonance imaging. The PGV of the patient group was significantly larger than that of the controls (p = 0.023). There was no statistically significant difference in PGV between mild and moderate ID. A moderate and positive correlation was found between Weschler Intelligence Scale for Children-revised (WISC-R) performance score and PGV (p = 0.049, r = 0.313) only in the patient group. In the receiver operating characteristic analysis, the area under the curve was 0.648, and the sensitivity was 70.0%, and the specificity was 60.0%. In conclusion, this study demonstrated that the increased PGV levels were associated with autism spectrum disorder (ASD) and PGV could be a risk factor in the aetiology of ID. Further research with larger sample sizes is needed to clarify this issue.

Four heterozygous de novo variants in ASXL3 identified with Bainbridge–Ropers syndrome and further dissecting published genotype–phenotype spectrum

Bainbridge–Ropers syndrome (BRPS) is a recently described neurodevelopmental genetic disorder associated with de novo truncating variants in additional sex combs like 3 (ASXL3) on chromosome 18q12.1. Trio-based exome sequencing was conducted on patients admitted to the Children’s Hospital Affiliated to Shandong University and diagnosed with unexplained intellectual disabilities or developmental delay between June 2022 and January 2024. De novo truncation of ASXL3 was identified in four patients, and the pathogenic variants and their de novo status were validated using Sanger sequencing. Comprehensive clinical phenotype–genotype information of all previously reported patients with BRPS was collected and summarized. The common clinical manifestations observed in the four patients included language and intellectual disabilities or psychomotor retardation. Genetic analysis revealed that patient 1 carried a de novo heterozygous variant, c.1667_1668del (p.Thr556Arpfs*3), whereas patient 2 had a novel heterozygous frameshift variant of ASXL3, c.3324del (p.Lys1109Serfs*34). These two variants have not been documented to date. Additionally, patients 3 and 4 exhibited a de novo variant, c.4678C > T (p.Arg1560Ter). Based on the combined assessment of clinical phenotypes and genetic testing results, it was postulated that all four children presented with BRPS syndrome caused by pathogenic variations in ASXL3. The present study complements the range of ASXL3 mutational and phenotypic spectra in the population, highlighting subtle distinctions in clinical manifestations between Chinese patients and other racial groups. The reporting of additional cases will contribute to further elucidating the function of ASXL3 and establishing a solid foundation for clinical diagnosis and treatment.

Insights From a Novel Splicing Variant and Recurrent Arginine Variants in the CHD3 Gene Causing Snijders Blok-Campeau Syndrome.

Snijders Blok-Campeau syndrome (SNIBCPS, OMIM#618205) is an autosomal dominant neurodevelopmental disorder attributed to pathogenic variants in the chromodomain helicase DNA binding protein 3 (CHD3) gene. To date, more than 100 individuals have been diagnosed with SNIBCPS. The syndrome is characterized by intellectual disability, global developmental delay, speech or language impediments, and dysmorphic features associated with macrocephaly. Additionally, affected individuals may exhibit behavioral issues, hypotonia, and autistic traits. A novel splicing variant (c.5590+1G > T) in the C-terminal 2 region of the CHD3 gene was identified in a patient predominantly exhibiting autistic characteristics. Invitro minigene splicing experiments conducted in HEK293 cells revealed that aberrant splicing resulted in the formation of a cryptic site 46 nucleotides downstream of the 5' splice site. This alteration was predicted to disrupt the reading frame by eliminating the physiological stop codon, consequently causing an extension in protein translation. Furthermore, an additional patient presenting with hypotonia, dysmorphic features, and global developmental delay was documented. This patient harbored a missense variant in the helicase C-terminal domain, c.3505C > T (p. Arg1169Trp). The pathogenic variant was anticipated to impact chromatin remodeling capacity and enzyme activity. Given the high prevalence of arginine residue pathogenic variants in the CHD3 protein and its notable propensity for binding and storing ATP molecules, intriguing insights into the potential effects of arginine residue pathogenic variants on phenotypes are provided. These findings contribute to a more comprehensive understanding of the genetic landscape of SNIBCPS while elucidating potential molecular mechanisms underlying the syndrome.

Contraceptive digital pills and sexual and reproductive healthcare of women with mental disabilities: Problem or solution?

For years, the sexual and reproductive health of women with intellectual and developmental disability or disabilities has been insufficiently addressed by institutions and family members due to a lack of information, training, and, sometimes, religious issues. In this context, contraceptive digital pills can enhance the sexual and reproductive control of this population group. Digital pills could help to improve adherence to treatments aimed to prevent unwanted pregnancies, as well as allowing women and their caregivers to exert better drug intake control. However, there are some ethical risks to consider that may outweigh these benefits. This study sets out to explore the ethical considerations that should be taken into account in the case of a potential roll-out of contraceptive digital pills as a way of improving the sexual and reproductive health of these women.

Caregiver-Implemented Interventions to Improve Daily Living Skills for Individuals With Developmental Disabilities: A Systematic Review.

Many individuals with intellectual and developmental disabilities (DD) encounter difficulties in performing daily living skills, which limits their self-sufficiency and autonomy. Caregivers, such as parents, are often the individuals who interact with individuals with DD the most during daily living skills routines. Therefore, it is critical to teach caregivers to implement daily living skills interventions with their children. A systematic review of the literature related to caregiver-implemented daily living skills interventions yielded 38 articles. Of those, 20 articles, with 21 experiments, were rated as high quality based on What Works Clearinghouse design standards. Behavior skill training was the most common strategy used to teach caregivers to implement interventions. Common daily living skills interventions included prompting, reinforcement, and task analysis. The most common form of prompting was verbal prompting, and the most common schedule of reinforcement was a continuous schedule of reinforcement. Of the 21 high-quality experiments, 86% demonstrated caregiver-implemented interventions yielded improvements in daily living skills. Several studies demonstrated generalization and maintenance of daily living skills. Implications for research and practice are discussed.