Submicroscopic 11p13 deletion including the elongator acetyltransferase complex subunit 4 gene in a girl with language failure, intellectual disability and congenital malformations: A case report

BACKGROUND We described the main features of an infant diagnosed with facial dysmorphic,language failure,intellectual disability and congenital malformations to strengthen our understanding of the disease.Currently,treatment is only rehabilitation and surgery for cleft lip and palate.CASE SUMMARY The proband was a 2-years-8-months-old girl.Familial history was negative for congenital malformations or intellectual disability.The patient had microcephaly,upward-slanting palpebral fissures,depressed nasal bridge,bulbous nose and bilateral cleft lip and palate.Brain magnetic resonance imaging showed cortical atrophy and band heterotopia.Her motor and intellectual development is delayed.A submicroscopic deletion in 11p13 involving the elongator acetyltransferase complex subunit 4 gene(ELP4)and a loss of heterozygosity in Xq25-q26.3 were detected.CONCLUSION There is no treatment for the ELP4 deletion caused by a submicroscopic 11p3 deletion.We describe a second case of deletion of the ELP4 gene without aniridia,which confirms the association between ELP4 gene with several defects and absence of this ocular defect.Additional clinical data in the deletion of the ELP4 gene as cleft palate,facial dysmorphism,and changes at level brain could be associated to this gene or be part of the effect of the recessives genes involved in the loss of heterozygosity region of Xq25-26.3.

Empirically supported psychological treatments:The challenges of comorbid psychiatric and behavioral disorders in people with intellectual disability

This paper reviews the current state of knowledge on psychological interventions with empirical evidence of efficacy in treating common psychiatric and behavioral disorders in people with intellectual disability(ID)at all stages of their life.We begin with a brief presentation of what is meant by psychiatric and behavioral disorders in this population,along with an explanation of some of the factors that contribute to the increased psychosocial vulnerability of this group to present with these problems.We then conduct a review of empirically supported psychological therapies used to treat psychiatric and behavioral disorders in people with ID.The review is structured around the three generations of therapies:Applied behavior analysis(e.g.,positive behavior support),cognitive behavioral therapies(e.g.,mindfulness-based cognitive therapy),and contextual therapies(e.g.,dialectical behavior therapy).We conclude with some recommendations for professional practice in the fields of ID and psychiatry.

Students With Intellectual Disability Learn How to Write With Motivation and Joy

Reading and writing can be seen as two sides of the same coin but have different demands for the writer and the reader to handle.The aim of this article is to focus on writing,how to create texts when students have intellectual disabilities and how students with intellectual disabilities have improved their writing skills through an intervention study.Writing will be highlighted from different perspectives,mostly about how writing can be supported through a structural way of working.When it comes to reading and reading difficulties,many studies have been done from different aspects of these topics.Most of these studies are among students with typical intellectual development.Studies about writing development and difficulties are fewer in number than studies about reading,but these are also mostly about children with typical development.When it comes to students with intellectual disability,studies about reading are rare and even rarer when it comes to writing.With this article,we will shed light on how writing difficulties can occur in general development and also when students have intellectual disability.The intervention study presented in this article will give some examples of how teachers can support every student’s writing development.

Neurobiology of Neuronal Network Alteration in Intellectual Disability Related to Fetal Alcohol Spectrum Disorders

The molecular and cellular mechanisms by which alcohol produces its deleterious effects on neuronal networks are only now beginning to be understood. This review focused on alcohol-induced neurobiological alterations on neuronal network components underlying information processing, for further understanding of intellectual disability related to FASD. Abnormal neurodevelopmental events related to alcohol-damaged fetal brain included neurogenesis inhibition, aberrant migration, impaired differentiation, exacerbated apoptosis, impaired axon outgrowth and branching altering synaptogenesis and synaptic plasticity, abnormal GABAergic interneurons triggering synaptic inhibitory/excitatory imbalance, reduced myelinogenesis causing injured white matter in prefrontal lobe and atrophied corpus callosum compromising interhemispheric information transfer, the whole compromising neuronal network scaffolding which may lead to biased information processing with deficits in executive function. What added to these abnormalities are smaller gray matter and reduced hippocampus, resulting in cognition and memory failures. As a whole, these developmental disorders may underlie intellectual disability related to FASD. In rodents, these neuronal network components matured mainly during the second and third trimesters equivalents of human gestation. Transferability of results from animal to human was also discussed. It was hoped that the understanding of alcohol-induced neuronal networks failure mechanisms during the developing brain may lay a foundation for prospective new treatments and interventions.

Strengthening Social Skills in Students With an Intellectual Disability in Secondary Education

During recent decades, one of education＇s most important issues is the idea of inclusion regarding the students＇ full participation to the mutual school environment. In addition, in the international scientific bibliography, it is stated that children with Intellectual Disability （ID） can integrate socially at school. However, the social benefits of inclusive education cannot always be reached. Studies have shown that just putting students with ID in a common school is not always adequate, as their social abilities are insufficient and because of that interventions are required. In this paper, we will examine school inclusion of students with ID having in mind that it is connected firstly to the modification of educational techniques using a Targeted, Individual, Structured, Integrated Program for Students with Special Educational Needs （TISIPfSENs）. We will focus to the enhancement of their social skills facing school as one of their educational areas inside the community. The results showed that educational interventions that are focused on the enforcement of social skills are a basic priority for the inclusion of students with ID inside the school community.

Prevalence of intellectual disability in India:A meta-analysis

BACKGROUND Burden due to intellectual disability(ID) is only third to the depressive disorders and anxiety disorders in India. This national burden significantly contributes to the global burden of ID and hence one has to think globally and act locally to reduce this burden. At its best the collective prevalence of ID is in the form of narrative reviews. There is an urgent need to document the summary prevalence of ID to enhance further policymaking, national programs and resource allocation.AIM To establish the summary prevalence of ID during the past 60 years in India.METHODS Two researchers independently and electronically searched Pub Med, Scopus, and the Cochrane library from January 1961 to December 2020 using appropriate search terms. Two other investigators extracted the study design, setting, participant characteristics, and measures used to identify ID. Two other researchers appraised the quality of the studies using the Joanna Briggs Institute critical appraisal format for Prevalence Studies. Funnel plot and Egger’s regression test were used to ascertain the publication and small study effect on the prevalence. To evaluate the summary prevalence of ID, we used the random effects model with arcsine square-root transformation. Heterogeneity of I^(2)≥ 50% was considered substantial and we determined the heterogeneity with meta-regression. The analyses were performed using STATA(version 16).RESULTS Nineteen studies were included in the meta-analysis. There was publication bias;the trim-and-fill method was used to further ascertain bias. Concerns with control of confounders and the reliable measure of outcome were noted in the critical appraisal. The summary prevalence of ID was 2% [(95%CI: 2%, 3%);I^(2)= 98%] and the adjusted summary prevalence was 1.4%. Meta-regression demonstrated that age of the participants was statistically significantly related to the prevalence;other factors did not influence the prevalence or heterogeneity.CONCLUSION The summary prevalence of ID in India was established to be 2% taking into consideration the individual prevalence studies over the last six decades. This knowledge should improve the existing disability and mental health policies, national programs and service delivery to reduce the national and global burden associated with ID.

Cytogenetic Diagnosis and Analysis of the Clinical Profile of Individuals with Non-down Syndrome Intellectual Disability

Chromosomal alterations are the main causes of genetic diseases. One of the characteristics of certain genetic syndromes is ID （intellectual disability） presented by the individual in varying degrees. The study of the ID, its etiology, association or not with chromosomal abnormalities and a clinical diagnosis associated with the examination of karyotype are important aspects to consider when providing genetic counseling for families. Due to the lack of similar studies and of easy access to cytogenetic services for the Amazonian population, this study aimed to contribute to the advancement of this line of study in the state, analyzing the karyotype of individuals with ID, not Down Syndrome treated at the APAE-Manaus and identifying the main types of chromosomal alterations in the individuals analyzed. Analyzes were performed of the clinical diagnosis through investigation of the data from the interview and medical records as well as analysis of the karyotype of 31 patients with non-Down syndrome ID, attended in the APAE-Manaus. Of these subjects, 20 were female and 11 male. The results showed only 2 cases of chromosome abnormalities are detectable by classical cytogenetics, one of mosaic Turner syndrome and one a heterochromatic variant. It is therefore necessary to complement the study with the addition of molecular techniques for the investigation of microdeletions and/or other alterations not detectable through the banding technique, mainly for individuals whose dysmorphisms indicate a suspected syndrome.

Compound heterozygous mutations of NTNG2 cause intellectual disability via inhibition of the CaMKII signaling

Netrin-G2 is a membrane-anchored protein known to play critical roles in neuronal circuit development and synaptic organization.In this study,we identify compound heterozygous mutations of c.547delC p.(Arg183Alafs*186)and c.605G>A,p.(Trp202X)in NTNG2 causing a syndrome exhibiting developmenta delay,intellectual disability,hypotonia,and facial dysmorphism.To elucidate the underlying cellular and molecular mechanisms,CRISPR-Cas9 technology is employed to generate a knock-in mouse mode expressing the R183Afs and W202X mutations.We report that the Ntng2^(R183Afs/W202X)mice exhibit hypo tonia and impaired learning and memory.We find that the levels of CaMKII and p-GluA1^(Ser831)are decreased,and excitatory postsynaptic transmission and long-term potentiation are impaired.To increase the activity of CaMKII,the mutant mice receive intraperitoneal injections of DCP-LA,a CaMKII agonist,and show improved cognitive function.Together,our findings reveal molecular mechanisms of how NTNG2deficiency leads to impairments of cognitive ability and synaptic plasticity.

Performance of the Autism Spectrum Rating Scale and Social Responsiveness Scale in Identifying Autism Spectrum Disorder Among Cases of Intellectual Disability

The Autism Spectrum Rating Scale(ASRS) and the Social Responsiveness Scale(SRS) have been widely used for screening autism spectrum disorder(ASD) in the general population during epidemiological studies, but studies of individuals with intellectual disability(ID) are quite limited. Therefore, we recruited the parents/caregivers of 204 ASD cases, 71 ID cases aged 6–18 years from special education schools, and 402 typically developing(TD) children in the same age span from a communitybased population to complete the ASRS and SRS. The results showed that the ID group scored significantly lower on total and subscale scores than the ASD group on both scales(P \ 0.05) but higher than TD children(P \ 0.05).Receiver operating characteristic analyses demonstrated a similar fair performance in discriminating ASD from ID with the ASRS(area under the curve(AUC) = 0.709,sensitivity = 77.0%, specificity = 52.1%, positive predictive value(PPV) = 82.2%) and the SRS(AUC = 0.742,sensitivity = 59.8%, specificity = 77.5%, PPV = 88.4%).The results showed that individuals with ID had clear autistic traits and discriminating ASD from ID cases was quite challenging, while assessment tools such as ASRS and SRS, help to some degree.

The Use of Goal Attainment Scaling in the Acupuncture of Children with Intellectual Disability

Objective: The therapeutic effect of acupuncture is often evaluated based on the experience and judgment of acupuncturists and the subjective feelings of patients. Thus, we investigated the suitability of goal attainment scaling(GAS), an objective outcome measurements, to evaluate the responsiveness of children with intellectual disability to acupuncture therapy. Methods: This is an assessor-blinded, single-group cohort study that included 17 children with intellectual disabilities. The therapeutic effect of acupuncture was assessed by the T scores of GAS at four time points during the 3-month treatment. The responsiveness of GAS to acupuncture therapy was measured using the standardized response mean(SRM). Results: Compared with control, the 4-, 8-, and 12-week scores improved significantly after treatment(P < 0.01, P≤0.001,P≤0.001), with significant differences between each month(P < 0.01, P≤0.001, P≤0.001). Furthermore, all periods assessed GAS(to measure the therapeutic effect of acupuncture) showed marked responsiveness(SRMs >0.8). Conclusion: GAS is responsive in evaluating individual changes in the acupuncture treatment of children with intellectual disabilities. It is a feasible tool to match both the needs of children with intellectual disabilities and the clinical characteristics of acupuncture.

A Novel MYCN Variant Associated with Intellectual Disability Regulates Neuronal Development

The V-MYC avian myelocytomatosis viral-related onco- gene, a neuroblastoma-derived gene （MYCN, MIM： 164840） located on chromosome 2p24, was previously found to be associated with Feingold syndrome 1 （FGLDS1, MIM： 164280） [1]. FGLDS1 is an autosomal dominant disorder characterized by variable combinations of microcephaly, limb malformations, esophageal and duodenal atresias, and learning disabilities. Cardiac and renal malformations, vertebral anomalies, and deafness have also been described in a minority of patients [2]. Despite the involvement of intellectual disability in FGLDS1, the molecular mechanisms of the MYCN gene in regulating brain development remain largely unclear.Some truncated mutations in the N terminus of the MYCN have been identified in FGLDS1 [1, 3].

Associated Factors of Dental Caries among Intellectually Disabled Persons in Specialized Centers of Ouagadougou

Introduction: Several studies have reported a high prevalence of dental caries among the people with intellectual disabilities. In order to identify the sociodemographic, clinical and behavioral factors associated with it, we conducted a study in specialized centers welcoming subjects with intellectual disabilities in Ouagadougou (Burkina Faso). Objectives: The objective of this study was to identify the factors associated with it among intellectually disabled in the specialized centers of Ouagadougou. Methods: The study was cross-sectional analytical. The survey took place between November 2020 and January 2021 among people with intellectual disabilities in reception centers receiving a grant from the Ministry of Women, National Solidarity, Family and Humanitarian Action. Data collection was done with a questionnaire adapted from the World Health Organization (WHO) and dental caries was recorded according to WHO criteria in decayed, missing or filled teeth generating a DMF index. Logistic regression was used to identify factors associated with the presence of dental caries. Results: A total of 193 participants were included in the study with an average age of 12.4 years ± 7.9. The overall prevalence of caries measured with the DMF index was 58.6% 95% CI [51.2 - 65.8]. It was significantly associated with female gender (OR = 4.2;95% CI [1.4 - 12.5], p = 0,01), the clinical form of mental illness (epilepsy OR = 3.8 95%;CI [1.2 - 12.7], p = 0,02, trisomy OR = 5.0;95% CI [1.1 - 22.9], p = 0,03, motor autonomy OR = 0.2 95%;CI [0.1 - 0.7], p = 0,01) and at use of toothpaste OR = 9.33;95% CI [1.05 - 82.7], p = 0,04. Conclusion: Dental caries remains a very present pathology in most people living with an intellectual disability. Also, it is necessary to put in place prevention strategies to reduce its prevalence and improve access to oral care for these people.

The Role of Music Therapy in Supporting Intellectually Disabled Youth in Senegal

Introduction: Music therapy is a practice for helping and supporting people with intellectual and relational difficulties. This study illustrated the benefits of music therapy for young people living with intellectual disabilities (YLID) in an African context. Methodology: This study investigated six young individuals with intellectual disabilities who had undergone three years of music therapy. They were participants in the inclusive non-academic training program at the National School of Arts in Dakar from 2017 to 2019. Data collection utilized individual interviews with the youths, evaluation grids from teachers and psychiatrists. Guardians provided informed consent along with the assent of the young participants. Results: The six young were aged between 18 and 30 years old, with an average age of 24.6 years. Four of the YLID were male. Three young people with intellectual disabilities had delayed psychomotor development. Observations revealed the beneficial influence of music therapy on the health and well-being of young individuals. Music played a role in alleviating stress and anxiety among youth with intellectual disabilities (YLID), enhancing their mood and mental health. It assisted in navigating challenging situations and heightened alertness among YLID. Additionally, music therapy contributed to improvements in dyslexia, fine and gross motor skills, and memory development among intellectually disabled youth, ultimately facilitating their integration into society. Conclusion: In light of our results, music therapy makes a major contribution to the empowerment of YLID. Engaging in musical activities helps young people connect with others through instrumental expression and a sense of accomplishment. By facilitating music therapy, it becomes possible to combat discrimination and stigmatization, thus promoting the social inclusion of intellectually disabled youth. Therefore, it is important to promote music therapy in Senegal to meet the needs of YLID.

Understanding Behavioral Manifestations of Obsessive-Compulsive Disorder in People with Intellectual Disabilities—A Qualitative Study

Background: There is limited knowledge about obsessive-compulsive disorder (OCD) in people with intellectual disabilities (IDs). This paper describes the manifestation of compulsive behaviors associated with OCD at the behavioral level in people with ID in institutionalized settings. The aim was to gain nuanced insight into appropriate understanding and classification in this specific context, and derive implications for research and practice. Methods: Individual cases of people with ID (n = 7) were studied to assess compulsive symptoms through two days of on-site observation of the person with ID within the institution, guided group discussions (n = 28), and semi-structured interviews with key informants and caregivers of the person with ID (n = 20). Caregiver ratings of the compulsive behavior checklist were compiled. Data were analyzed using qualitative content analysis. Results: All forms of OCD were present. Characteristics of compulsive behaviors in people with ID at the behavioral level included less complex and more obvious compulsive acts, immediate responses, signs of tension, motor restlessness, facial expression changes, repetition, need for predictability, time-consuming behaviors, and aggressive reactions when these acts were interrupted. Some of the compulsive behaviors corresponded to the ICD-11 OCD code 6B20, and others to compulsions as a psychological symptom (MB23.4). Conclusions: OCD may manifest atypically at the behavioral level in people with ID, posing significant challenges for accurate classification due to symptom ambiguity. Follow-up differential diagnostic studies are needed to more accurately identify and differentiate OCD symptoms in people with ID. Further, disorder-specific guidelines for recognizing OCD in people with ID are needed for institutionalized settings without psychiatric-psychotherapeutic expertise.

CNKSR2 interactome analysis indicates its association with the centrosome/microtubule system

The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding domains.Variants of the CNKSR2 gene have been implicated in neurodevelopmental disorders,particularly intellectual disability,although the precise mechanism involved has not yet been fully understood.Research has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane,thereby influencing synaptic signaling and the morphogenesis of dendritic spines.However,the function of CNKSR2 in the cytoplasm remains to be elucidated.In this study,we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of CNKSR2.Through a combination of bioinformatic analysis and cytological experiments,we found that the CNKSR2 interactors were significantly enriched in the proteome of the centrosome.We also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker CEP290.Subsequent colocalization analysis confirmed the centrosomal localization of CNKSR2.When we downregulated CNKSR2 expression in mouse neuroblastoma cells(Neuro 2A),we observed significant changes in the expression of numerous centrosomal genes.This manipulation also affected centrosome-related functions,including cell size and shape,cell proliferation,and motility.Furthermore,we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum disorder.Our findings establish a connection between CNKSR2 and the centrosome,and offer new insights into the underlying mechanisms of neurodevelopmental disorders.

Family empowerment and associated factors in Japanese families raising a child with severe motor and intellectual disabilities

Objectives:Family caregivers raising children with severe motor and intellectual disabilities(SMID)experience the enormous burden of care.The concept of family empowerment is one of the important assessment indexes of family nursing from the perspective of providing comprehensive support for these families.The objective of this study was to identify the factors associated with the empowerment of families raising a child with SMID in Japan.Methods:We conducted a nationwide questionnaire survey involving 1659 primary caregivers raising a child with SMID through 89 special schools.We assessed the main outcomes using the Family Empowerment Scale(FES).We then conducted a multiple linear regression analysis to reveal the factors associated with family empowerment.Results:In total,1362 primary caregivers were included in our study.Our results show that factors contributing to high FES scores are higher age of the primary caregiver,higher education,greater recognition of regional support,lower childcare burden,higher utilization of home visit services,higher usage of a childcare institution,higher household income,and stronger family bonding.Conclusion:Healthcare professionals should carefully assess the state of family empowerment of the primary caregivers who are younger and those who have low education,low household income,high childcare burden,and fragile bonding with the family.Second,they should encourage such families to use regional support resources for childcare.That is,policy makers should consider ways to promote home visits and institutional services for the care of children with SMID,aiming especially for the provision of well-coordinated care and services.

Utilizing the China Health and Retirement Longitudinal Study (CHARLS) to Understand the Aging of People Living in the Community with Intellectual and Developmental Disabilities

There remain challenges in understanding the aging lives of people with intellectual and developmental disabilities. Method: A cross-sectional comparison of people with and without I/DD was created using China Health and Retirement Longitudinal Study (CHARLS). A definition of I/DD was established, three samples were created: those with an assigned/described intellectual and developmental disability prior to age 22 years;those with similar impairments at and after age 22 years;and those in the population without an assigned/described impairment. Findings: Those with I/DD appeared to have greater health needs on initial analysis. People with an impairment similar to I/DD but occurring after age 22 years had the same or greater needs in subsequent analyses. Both groups had greater needs than those with no identified disability. Discussion: There must be greater efforts to discover those with I/DD who are already in existing datasets, greater attention to the full range of lives led by people with I/DD and inclusion of data from a broader range of countries.

Depressive symptoms, social support, cognitive function, and stigma: predictors of resilience in caregivers of children with intellectual disabilities

Objective:Family plays an important role in taking care of children with intellectual disabilities(IDs).Resilience supports coping strategies for caregivers with their children caring.However,factors influencing the resilience of caregivers with ID in Thailand are yet to be identified.Therefore,the aim of this study was to identify the predictors of resilience in caregivers of children with moderate to severe ID.Methods:A cross-sectional study was implemented in caregivers of children with ID aged 18 years and older who had children diagnosed with ID aged 6–18 years and classified as moderate to severe ID.Descriptive statistic and multiple linear regression were used for data analysis.Results:The study sample consisted of 85 caregivers who took care of their children older than 5 years(95.30%).Depression,social support,cognitive function,and stigma could predict the resilience(F[4,80]=26.79,P<0.001)and explain the variability of resilience by 57.3%.Conclusions:Caregivers have to take care of their children for a long period,which could develop a burden to the caregivers.The resilience and influencing factors should be monitored and managed by developing a campaign to promote caregivers’health and well-being.

A Study of Radiation-Induced Instability for the Gene Locus Associated with Intellectual Disorders or Developmental Delays

Multiplex Ligation-Dependent Probe Amplification (MLPA) was used to study the integrity of the chromosomes for two WIL2-derived lymphoblastoid cell lines (TK6 and WTK1) in the presence and absence of ionizing radiation. WTK1 cells contain a p53 mutation, whereas the TK6 cell line has the native p53 tumor-suppressor gene. Each cell line was isolated pre- and post-irradiation (2 and 3 Gy) and analyzed by MLPA. Using probes that target specific regions on chromosomes associated with a distinct subset of microdeletions and microduplications either established or thought to be responsible for intellectual disability or developmental delay, we have demonstrated that WTK1 and TK6 are not impacted in the same way by irradiation. Instead, each cell line presents its own unique MLPA profile. The most notable differences are the appearance of nine unique probe signals only seen in WTK1 cells. These results are important in the study of how different cell lines can be affected in significantly different ways depending on the presence or absence of wild type p53.

Healthy lifestyle for people with intellectual disabilities through a health intervention program

There are well known gaps related to health care service and public health interventions for people with Intellectual Disabilities (ID), but there is still lack of research information of what nurses can do to reducing health disparities of persons with ID. The present study aimed at exploring the views of people with ID about a healthy lifestyle, exercise, and to take part in a health promotion program. A qualitative method was an appropriate method for capturing the informants’ points of view. Participants were adults with intellectual disability who would be able to give their consent verbally and in written form. Women (n = 7) and men (n = 6). Data were collected from focus group interviews and analysed according to a qualitative content analysis of the tape-recorded and verbatim transcribed interviews. The participants took part in four workshops about healthy food, and ten physical activities addressing the connection to physical, social and emotional health. The results of the focus group interviews show that participants have knowledge about the importance of a healthy lifestyle for good health including physical activity and healthy food. Participants also describe social interaction and self-determination as important aspects in their life. It could then be concluded that the health promotion program result point at consciousness about a healthy lifestyle. There is still lack of research information of what public health nurses can do to reducing health disparities of persons with ID. Public health nurses work in community-based services and therefore they also might support persons with ID through health intervention programs.