Significant Intellectual Disability Research Articles

A Gad2 specific Slc6a8 deletion recapitulates the contextual and cued freezing deficits seen in Slc6a8-/y mice

The creatine (Cr)-phosphocreatine shuttle is essential for ATP homeostasis. In humans, the absence of brain Cr causes significant intellectual disability, epilepsy, and language delay. Mutations of the creatine transporter (SLC6A8) are the most common cause of Cr deficiency. In rodents, Slc6a8 deletion causes deficits in spatial learning, novel object recognition (NOR), as well as in contextual and cued freezing. The mechanisms that underlie these cognitive deficits are not known. Due to the heterogeneous nature of the brain, it is important to determine which systems are affected by a loss of Cr. In this study, we generated mice lacking Slc6a8 in GABAergic neurons by crossing Slc6a8FL mice with Gad2-Cre mice. These Gad2-specific Slc6a8 knockout (cKO) mice, along with the ubiquitous Slc6a8 KO (Slc6a8-/y), Gad2-Cre+, and wild-type (WT) mice were tested in the Morris water maze, NOR, conditioned freezing, and the radial water maze. Similar to the Slc6a8-/y mice, cKO mice had reduced contextual and cued freezing compared with WT mice. The cKO mice had a mild spatial learning deficit during the reversal phase of the MWM, however they were not as pronounced as in Slc6a8-/y mice. In NOR, the Gad2-Cre mice spent less time with the novel object, similar to the reduced novel time in the cKO mice. There were no changes in radial water maze performance. Slc6a8 deletion in GABAergic neurons is sufficient to recapitulate the conditioned freezing deficits seen in Slc6a8-/y mice.

Corrigendum to “Investigating the Alignment Between English Language Arts Curricula Developed for Students With Significant Intellectual Disability and the CCS”

Corrigendum to “Investigating the Alignment Between English Language Arts Curricula Developed for Students With Significant Intellectual Disability and the CCS”

Promising Strategies for Teaching Augmentative and Alternative Communication in Inclusive Educational Settings: A Systematic Review.

The purpose of this article was to conduct a systematic review of the literature on teaching or increasing the use of augmentative and alternative communication (AAC) by students with significant intellectual disabilities and complex communication needs (CCNs) within inclusive school settings. A systematic review of research literature from 1998 to 2022 was completed using multiple electronic databases, as well as citation chaining and cited author reference searches. Three hundred two articles were located with 17 meeting criteria for inclusion in this systematic review. Articles were initially screened by one author for potential inclusion; the remaining 83 were coded by one author and reviewed for consensus by three authors for inclusion in this review. Articles were analyzed and rated regarding both level of research design and quality of methodology. All studies reported positive outcomes, with students with significant intellectual disabilities and CCN, of AAC intervention implemented in an inclusive setting. Fourteen over 17 studies were single-case designs with an average rating of 76% on the Single-Case Experimental Design measure of methodological quality. Less than half of the studies assessed generalization of subject learning. Review of interventions used in the studies, however, revealed the majority of studies utilized packages of interventions, making it difficult to determine the effectiveness of individual approaches. This systematic review indicates there are promising interventions within inclusive settings for improved use of AAC by students with significant intellectual disabilities and CCN. Further research is needed, however, to obtain more data on generalization of student gains as well as to determine which specific interventions might be the most successful for this population of students in inclusive settings.

Evidence and Recommendation for Guanidinoacetate Methyltransferase Deficiency Newborn Screening.

Guanidinoacetate methyltransferase (GAMT) deficiency is an autosomal recessive disorder of creatine biosynthesis due to pathogenic variants in the GAMT gene that lead to cerebral creatine deficiency and neurotoxic levels of guanidinoacetate. Untreated, GAMT deficiency is associated with hypotonia, significant intellectual disability, limited speech development, recurrent seizures, behavior problems, and involuntary movements. The birth prevalence of GAMT deficiency is likely between 0.5 and 2 per million live births. On the basis of small case series and sibling data, presymptomatic treatment with oral supplements of creatine, ornithine, and sodium benzoate, and a protein-restricted diet to reduce arginine intake, appear to substantially improve health and developmental outcomes. Without newborn screening, diagnosis typically happens after the development of significant impairment, when treatment has limited utility. GAMT deficiency newborn screening can be incorporated into the tandem-mass spectrometry screening that is already routinely used for newborn screening, with about 1 per 100 000 newborns screening positive. After a positive screen, diagnosis is established by finding an elevated guanidinoacetate concentration and low creatine concentration in the blood. Although GAMT deficiency is significantly more rare than other conditions included in newborn screening, the feasibility of screening, the low number of positive results, the relative ease of diagnosis, and the expected benefit of presymptomatic dietary therapy led to a recommendation from the Advisory Committee on Heritable Disorders in Newborns and Children to the Secretary of Health and Human Services that GAMT deficiency be added to the Recommended Uniform Screening Panel. This recommendation was accepted in January 2023.

Neuropsychological Characterization of Autosomal Recessive Intellectual Developmental Disorder 59 Associated with IMPA1 (MRT59).

Biallelic loss of function of IMPA1 causes autosomal recessive intellectual developmental disorder 59 (MRT59, OMIM #617323). MRT59 has been reported to present with significant intellectual disability and disruptive behavior, but little is known about the neurocognitive pattern of those patients. Thus, the aims of this study were: (1) to assess the cognitive profile of these patients, and (2) to evaluate their functional dependence levels. Eighteen adults, aged 37 to 89 years, participated in this study: nine MRT59 patients, five heterozygous carriers and four non-carrier family members. All of them were from a consanguineous family living in Northeast Brazil. All IMPA1 patients had the (c.489_493dupGGGCT) pathogenic variant in homozygosis. For cognitive assessment, the WASI battery was applied in nine MRT59 patients and compared to heterozygous carriers and non-carrier family members. Functional dependence was evaluated using the functional independence measure (FIM). Patients showed moderate to severe intellectual disability and severe functional disabilities. Heterozygous carriers did not differ from non-carriers. MRT59 patients should be followed up by health professionals in an interdisciplinary way to understand their cognitive disabilities and functional needs properly.

Practitioner-Implemented Video Prompting on Vocational Skills of Students With Significant Intellectual and Developmental Disabilities

Video prompting (VP) is an evidence-based practice, but few studies have included teachers and paraeducators as implementers. We adopted one of the single-case designs (multiple probe design) to evaluate the effectiveness of teacher and paraeducator-implemented VP on vocational skills for four high school students with significant intellectual and developmental disabilities. Experimental effects were demonstrated for all four students, but only two students met the mastery criterion. Individualized adaptations (i.e., priming, more frequent reinforcement) enabled two students to make further progress. The two students who met the mastery criterion maintained their performance after 2 weeks. These findings add to growing evidence that teachers and practitioners can effectively implement VP and suggest that individualized adaptations may be needed for some students with significant disabilities.

Внеурочная деятельность детей с выраженными нарушениями интеллекта в России: взгляд изнутри

The purpose of the article is to provide an assessment of the current state of extracurricular activity organization for children with significant intellectual disabilities in Russia using the method of the in-depth semi-structured interview. Scientific novelty lies in the following: the research was carried out within the humanistic sociocultural paradigm, in accordance with the principles of post-non-classical science. The analysis of the obtained data made it possible to make a “cut” of the current state of extracurricular activity, which, as the author hopes, will become the first step to the construction of its scientific picture. The problem of involvement of children with significant intellectual disabilities in extracurricular activity is considered holistically for the first time, including its socio-economic context, value-motivational orientation, and unique experience of the participants. The results are as follows: the research made it possible to reveal some peculiarities of the extracurricular activity of children with significant intellectual disabilities, to outline the range of its participants, its preferred types and forms, as well as the benefits and drawbacks of its current practice. A discrepancy was revealed between the requirements of the Federal State Educational Standard for Education of Students with Intellectual Disabilities in respect of the organization of extracurricular activity and its current state.

Profound Concerns about “Profound Autism”: Dangers of Severity Scales and Functioning Labels for Support Needs

Recently the Lancet published a Commission on the future of care and clinical research of autism, which included a side panel arguing for the adoption of “profound autism”, a term in- tended to describe autistic people who require constant supervision or care, thought to usually have significant intellectual disability, limited or no language, and an inability to advocate for themselves. This state-of-the-art review deconstructs problems with autism sublabels such as “profound autism” and low- and high-functioning labels. It then examines the communicative and cognitive capacities of minimally speaking autistic people, finding that such individuals can communicate (especially with responsive partners) and need nonverbal testing that allows them to demonstrate their potential strengths. It concludes with the ability of minimally speaking autistic people to self-advocate, and the influences of other people to both support and frustrate their communication.

Administration and Results of a State Alternate Assessment Based on Alternate Academic Standards in Science for Students Who Are Blind and Have Low Vision

Introduction: This study evaluated performance and engagement on the tactile science alternate assessment based on alternate academic standards (AA-AAS). This assessment was designed for students with significant intellectual disabilities and visual impairments (i.e., blindness and low vision). Four primary research questions guided this study. What were the demographic characteristics of the students who took the tactile AA-AAS-science? How did students who took the tactile AA-AAS-science perform? What accommodations, accessibility options, and communication strategies were employed in the administration of the tactile AA-AAS-science? Was there a correlation between any administration practices and improved student results? Methods: Thirty-four students with visual impairments and significant intellectual disabilities participated in the 2017 administration of the AA-AAS-science. Post-hoc analyses of the testing strategies were conducted using video recordings of each assessment. Videos were coded for accommodations, student performance, engagement, and appropriateness of the assessment for each student. Results: The tactile materials were the primary accommodation provided to students and were totally novel in 79.1% of the administrations. Students were not permitted to thoroughly explore materials. In many cases, the exam content was determined to be too difficult for the students. Discussion: This study supports the literature and suggests benefits in academic instruction for all students. For academic instruction to be meaningful, students need appropriate accommodations and consistent materials. Implications for Practitioners: Test administrators for assessments based on alternate academic standards should use familiar materials during a test administration, preferably the same materials used during instruction. It is also important for teachers to prepare students and allow for time to systematically explore tactile materials. Teachers can support students by including academic goals in the individualized education program.

Transgenic mice overexpressing mutant TDP-43 show aberrant splicing of neurological disorders-associated gene Zmynd11 prior to onset of motor symptoms.

Mutations in TDP-43 are known to cause Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). TDP-43 binds to and regulates splicing of several RNA including Zmynd11 . Zmynd11 is a transcriptional repressor and a potential E3 ubiquitin ligase family member, known for its role in neuron and muscle differentiation. Mutations in Zmynd11 have been associated with autism with significant developmental motor delays, intellectual disability, and ataxia. Here, we show that Zmynd11 is aberrantly spliced in the brain and spinal cord of transgenic mice overexpressing a mutant human TDP-43 (A315T), and that these changes occur before the onset of motor symptoms.

Communication in fragile X syndrome: Patterns and implications for assessment and intervention.

Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability and is associated with a high rate of autism diagnosis. Language delays have been noted in the areas of overall communication and the specific areas of receptive, expressive, and pragmatic language, as well as in development of speech sounds and literacy. It has been widely noted that those individuals with a diagnosis of both FXS and autism tend to have more significant intellectual disability and language disorder. In this study, the research exploring the FXS language phenotype is presented, and the roles of cognition, autistic symptomatology, and gender are highlighted as possible. Implications for assessment and intervention approaches based on the strengths and weaknesses of the FXS language phenotype are provided.

Hidradenitis suppurativa and suicide risk: a multivariate analysis in a disease with a high psychological burden.

BackgroundHidradenitis suppurativa (HS) is a disorder that can lead to serious sequelae and important comorbidities. It has been associated with different mental health conditions, such as depression, anxiety or completed suicide. The objective is to analyze the suicide risk (SR) among patients in a monographic HS consultation, as well as to establish individual association factors.MethodsPatients older than 18 years seen in our specific HS unit were consecutively included and invited to respond to the self-administered Beck hopelessness scale. Those patients with significant intellectual disabilities or severe mental health conditions, including a history of psychosis, were excluded. In addition, data related to the skin process were collected. Subsequently, it was studied whether there were significant differences between patients with absent–mild SR and those with moderate–severe SR and a logistic regression analysis was performed to determine the relationship of these variables with SR.ResultsA total of 136 patients were included in the study, 51.5% men. Of them, 21.3% presented a moderate or severe SR (score ≥ 9 in the Beck test). This risk was significantly related to having a previous or concomitant psychiatric disorder (OR = 2.586, 95% CI 1.044–6.409, p = 0.040) followed by the history of biological treatment (OR = 2.867, 95% CI 1.004–8.182, p = 0.049). The existence of other affected relatives was confirmed as a protective factor (OR = 0.377, 95% CI 0.150–0.951, p = 0.039).ConclusionsThe prevalence of SR in patients with HS is higher than that of the general Spanish population. The presence of a psychiatric disorder and the need for biological treatment are established as factors that increase SR, both of which can be interpreted as a more advanced disease. As a protective factor, the presence of other cases in the family is established, which suggests a greater normalization of the disease.

SHELTERED OR SUPPORTED EMPLOYMENT OPTIONS FOR SECONDARY EDUCATION STUDENTS WITH DISABILITIES?

The transformations in production and labour market of the last decades and the stormy global economic crisis have diversified and made particularly difficult the conditions for the inclusion of people with disabilities into the labour market and the society in general. Students with disabilities are at high risk of unemployment and a high percentage of those who work are employed in low-paid jobs. Employment is vital for them not only for a dignified life, but also for active participation in the community. In general, they face several limitations when trying to find or maintain a job they already have. It is a common belief that people with disabilities are not able to work, except perhaps in separate and Sheltered work environments (sheltered employment) where they will be safe enough. Such negative attitudes affect decisively their success or failure to secure a job or maintain an existing one. Sheltered employment has been at the core of the vocational training and employment system for young people with significant intellectual disabilities throughout the twentieth century, and most of them continue to work within isolated and Sheltered areas. According to our literature review the emergence of supported forms of employment has brought forward a real alternative, especially for students with intellectual disabilities. Unlike the sheltered and segregated forms of employment, supported employment enables paid employment, within the community, under conditions of continuous support, and has proven to be more effective over time. Based on the concept of self-determination it emphasizes personal strengths, goals and choices and the important role of the community for the improvement and development of the disabled individual.

Speech and language development and genotype-phenotype correlation in 49 individuals with KAT6A syndrome.

Pathogenic KAT6A variants cause syndromic neurodevelopmental disability. "Speech delay" is reported, yet none have examined specific speech and language features of KAT6A syndrome. Here we phenotype the communication profile of individuals with pathogenic KAT6A variants. Medical and communication data were acquired via standardized surveys and telehealth-assessment. Forty-nine individuals (25 females; aged 1;5-31;10) were recruited, most with truncating variants (44/49). Intellectual disability/developmental delay (42/45) was common, mostly moderate/severe, alongside concerns about vision (37/48), gastrointestinal function (33/48), and sleep (31/48). One-third (10/31) had a diagnosis of autism. Seventy-three percent (36/49) were minimally-verbal, relying on nonverbal behaviors to communicate. Verbal participants (13/49) displayed complex and co-occurring speech diagnoses regarding the perception/production of speech sounds, including phonological impairment (i.e., linguistic deficits) and speech apraxia (i.e., motor planning/programming deficits), which significantly impacted intelligibility. Receptive/expressive language and adaptive functioning were also severely impaired. Truncating variants in the last two exons of KAT6A were associated with poorer communication, daily-living skills, and socialization outcomes. In conclusion, severe communication difficulties are present in KAT6A syndrome, typically on a background of significant intellectual disability, vision, feeding and motor deficits, and autism in some. Most are minimally-verbal, with apparent contributions from underlying motor deficits and cognitive-linguistic impairment. Alternative/augmentative communication (AAC) approaches are required for many into adult life. Tailored AAC options should be fostered early, to accommodate the best communication outcomes.

STXBP1 Stop-Loss Mutation Associated with Complex Early Onset Movement Disorder without Epilepsy.

STXBP1 Stop-Loss Mutation Associated with Complex Early Onset Movement Disorder without Epilepsy.

Kidney Transplantation in a Patient With Tuberous Sclerosis Complex: A Case Report

Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disease caused by mutations of either of 2 genes, TSC1 and TSC2. Renal manifestations include angiomyolipomas (AMLs), multiple cysts, and renal cell carcinoma. AMLs increase bleeding tendency and the risk of renal insufficiency which end-stage develops in 1% of affected patients. A 38-year-old woman suffering from TSC since early childhood has developed multiple complications associated with this disease. The patient was diagnosed with brain tumor-giant cell astrocytoma-which was removed in 1992. In 2006, right nephrectomy was performed due to the unsuccessful right renal artery embolization after the massive hemorrhage into the AML. Moreover, the right idiopathic pneumothorax occurred twice. Therefore, the video-assisted thoracoscopic surgery and pleurodesis were conducted (2006, 2013). The patient is intellectually disabled and unable to make decisions on her own. Her legal guardians (parents) make all decisions associated with her treatment. Diagnostic and therapeutic procedures demanding cooperation were conducted under anesthesia. Because of end-stage renal failure, the patient required the renal replacement therapy (RRT). Preemptive kidney transplantation (KTx) was the best solution for this patient. Procedures such as hemodialysis and peritoneal dialysis were infeasible to perform due to the intellectual disability that inhibits essential cooperation. During KTx qualification tests, the expanding AML with risk of hemorrhage was noticed. The patient was qualified for simultaneous left nephrectomy and KTx from the living donor (her father). The surgery was performed on the 2nd of June 2020. The patient is looked after by her parents, stays in good general condition. The patient's creatinine level is maintained at 0.6 to 0.8 mg/dL. Patients with significant intellectual disability that prevents maintaining conscious cooperation who require RRT must have individually adjusted therapy. In the case of the presented patient, it was decided to perform the preemptive kidney transplantation from her determined father.

Multi‐tissue cytogenetic analysis for the diagnosis of mosaic Down syndrome: A case report

Less than one percent of individuals with Down syndrome exhibit mosaicism, a biological phenomenon that describes an individual who has two or more genetically distinct cell lines. The percentage of mosaicism in different tissues can impact the presence of clinical findings and hinder cytogenetic diagnosis. We report a case of mosaicism for trisomy 21 diagnosed after multi‐tissue cytogenetic analysis of peripheral blood and buccal mucosa, associated with significant intellectual disability, dysmorphic facial features, congenital heart defects, macropenis, and imperforate anus.

Agency through partnership in neurodiverse college learning communities

This article examines the work of creating collaborative learning partnerships that fully include students with intellectual disabilities. The article reviews the scholarship of partnership as a starting point in discussing learning environments that support students with significant intellectual disabilities—a group that has only recently been encouraged to enroll in colleges and universities. The authors—a faculty member and two former undergraduate mentors in the University Studies program at Portland State University—offer reflections on their time partnering as facilitators of courses that include students with intellectual disabilities. They then analyze those reflections in relation to the scholarship of partnership and special education. The article presents evidence that the partnership approach to learning is more fully realized through intentional investment in universal design for learning principles and extended support networks invested in collaboration and interpersonal relationship. These approaches effectively bring students with disabilities into the center of educational environments and maintain their agency in shaping their learning communities.

Administering Labor Analgesia Under General Anesthesia in an Intellectually Disabled Patient.

Maternal intellectual disability presents anesthetic challenges.1 A 19-year-old primigravida with significant intellectual disability presented with preterm premature rupture of membranes at 31 4/7 weeks of gestation and underwent induction of labor for chorioamnionitis. She was unable to tolerate bedside epidural placement. Intrapartum general anesthesia allowed for epidural catheter placement that provided adequate labor analgesia for a vaginal delivery. This report describes a unique approach to providing labor analgesia in the intellectually disabled patient.

Quality of Life for People with Disabilities: Why Applied Behavior Analysts Should Consider This a Primary Dependent Variable

Applied behavior analysis (ABA) is a natural science dedicated to using behavioral principles to address socially important problems. One area in which behavior analysts have made compelling gains in the last 50 years is in developing, evaluating, and disseminating effective interventions for people with significant intellectual and developmental disabilities. As the science of ABA has matured, many practitioners, researchers, and consumers have questioned how our field should define appropriate outcomes of behavioral interventions. In this article, we propose that improved quality of life should be the ultimate outcome for consumers receiving behavioral interventions. We explore definitions of quality of life and suggest some strategies that behavior analysts can apply to modify practices to more clearly center quality of life as an outcome variable.