Background: The SMARCB1 gene encodes a subunit of the BRG1-Associated Factor (BAF) complex, and mutations in this gene have been linked to Coffin-Siris Syndrome (CSS) type 3. CSS is characterized by a range of developmental disabilities, facial dysmorphic features, and feeding difficulties. There\'s been noted genotype-phenotype correlation in CSS, with cases involving SMARCB1 mutations often exhibiting more severe language impairment and intellectual disability. Method: We conducted a review of reported CSS type 3 cases and presented the first instance of CSS associated with a SMARCB1 variant wherein the patient exhibited normal intelligence and only mild selective neuropsychological deficits. The patient underwent evaluation for feeding challenges, growth delay, and dysmorphic features during their second year of life. Subsequently, CSS diagnosis was confirmed due to a de novo heterozygous c.568C > T (p.Arg190Trp) variant in the SMARCB1 gene. Due to learning difficulties, the patient underwent a comprehensive neuropsychological assessment, which was related to the retrospective reconstruction of her medical and developmental history. Results: The patient demonstrated normal intelligence and adaptive functioning, with specific deficits in arithmetic and selective difficulties in verbal learning and long-term memory. Feeding difficulties and language delay observed in early childhood showed significant improvement over time. Discussion: We discuss this case in relation to previously reported CSS type 3 cases, emphasizing neuropsychological aspects. It\'s evident that neuropsychological features of CSS can vary among affected individuals, highlighting the importance of personalized support and interventions tailored to specific cognitive and emotional needs by healthcare professionals. Our case suggests avenues for future research to identify specific modifiers of phenotypic expression to explain variability in intellect among patients and pinpoint potential targets for gene therapy.

BACKGROUND: In recognition of their status as a health disparities population, there is growing emphasis on conducting research inclusive of adults with intellectual disability to generate new knowledge and opportunities to improve health and equity. Yet they are often excluded from research, and human research participant protection experts and researchers lack agreement on effective consent protocols for their inclusion.
OBJECTIVE: We sought to identify approaches to consent in US-based social-behavioral research with adults with intellectual disability.
METHODS: We conducted a systematic review on approaches to self-consent with adults with intellectual disability published between 2009 and 2023, identified via searching eight databases and reference list hand searches. We identified 13 manuscripts and conducted a thematic analysis.
RESULTS: Our analysis identified themes related to guiding principles, strategies to enhance informed and voluntary consent, approaches to consent capacity, involving individuals subject to guardianship, and strategies for expressing decisions and enhancing ongoing decisions.
CONCLUSIONS: Manuscripts largely reflected an emphasis on identifying approaches to consent that reflect disability rights principles to promote the right to be included and make one\'s own decisions based on assessment of relevant information, risks and benefits, and to employ reasonable modifications to achieve inclusion. To avoid the risks of exclusion and advance the responsible inclusion of adults with intellectual disability, we make recommendations to align consent approaches anchored in contemporary thinking about human research participant protections, including through integration with disability rights.

Co-occurring intellectual/developmental disability (IDD) and overweight/obesity (OW/OB) is an important consideration of IDD psychiatric care. The relationship between OW/OB and comorbid diagnoses of Autism Spectrum Disorder (ASD) and/or IDD remains inadequately described in existing literature. The purpose of this study is to explore these co-occurring diagnoses. Improved understanding of associated comorbidities can guide clinicians toward interventions to minimize complications associated with OW/OB. We conducted a retrospective review of adult patients of a telepsychiatry clinic with IDD or ASD defined by DSM-5. ICD-10 diagnosis of IDD or ASD, demographics, BMI, comorbidities, and current medications were recorded. Binary logistic regression was used to estimate associations between each predictor and the outcomes overweight (body mass index (BMI) ≥ 25 kg/m2) and obesity (BMI ≥ 30 kg/m2). Prevalence of obesity in these 412 adults was 52.4% (95% CI 47.5, 57.3). There was a significant inverse relationship between IDD severity and the odds of each outcome (p < .001). 80.3% of patients were being actively treated with an antidepressant. Patients taking an antidepressant had twice the odds of obesity (adjusted OR 2.03, 95% CI 1.23, 3.41, p = .006). These findings provide a sense of urgency for prevention of OW/OB and its associated medical sequelae. Prevalence of obesity was higher in this sample compared to the general population. The inverse relationship between IDD severity and OW/OB warrants further research examining age, caregiver involvement, and access to care as potential modifiers.

The content of social studies encompasses various topics such as culture, citizenship, values, geography, and history. However, social studies has historically been an under-researched academic content area for students with intellectual disabilities. The aim of this study was to identify and summarize empirical research on social studies instruction for students with intellectual disabilities. We searched for articles in two electronic databases from 2000 to 2023. We applied seven inclusion criteria to 1709 articles that emerged in databases. A total of 13 empirical studies met the inclusion criteria. We conducted a narrative review across these 13 studies. Results showed that students with intellectual disabilities improved social studies skills through effective instructional strategies including graphic organizers, technology-based instruction, time delay, and task analysis. Also, social studies instruction for students with intellectual disabilities mostly focused on history and geography. We discussed the findings along with their limitations and provided recommendations for future research.

BACKGROUND: Providing menstrual education and guidance for menstrual management for girls and young women with intellectual disabilities is recommended to ensure smooth pubertal transitions and to support menstrual self-agency.
METHODS: The purpose of this systematic review is to explore menstrual education interventions for girls and young women with intellectual disabilities.
RESULTS: Nine studies were included. Interventions were provided in small groups (n = 4) and individually (n = 5). Most studies used dolls (n = 7) and task analysis (n = 7) to teach pad-replacement skills. All reported significant improvements in participant skills and/or knowledge following the intervention. Only one study addressed self-agency and self-esteem as an outcome of the intervention. Menstrual education for girls and young women with intellectual disabilities is largely focused on pad-replacement skills.
CONCLUSIONS: Further research is needed to understand the impact of menstrual health and hygiene education on variables apart from skill improvement such as self-agency and long-term health outcomes related to menstrual health.

Jaberi-Elahi syndrome is an extremely rare genetic disease caused by pathogenic variants in GTPBP2. The core symptoms of this disease are intellectual disability, motor development delay, abnormal reflexes, skeletal abnormalities, and visual impairment. In this study, we describe a three-year-old girl with a novel homozygous variant in GTPBP2 and a phenotype overlapping with Jaberi-Elahi syndrome. This variant (NM_019096.5:c.1289T > C, p.Leu430Pro) was identified by Whole Exome Sequencing and confirmed by Sanger sequencing although remains classified as VUS based on ACMG criteria. The proband demonstrated motor and intellectual developmental delay, muscle weakness, language disorder, facial dysmorphism, and poor growth. Hitherto, twenty-seven individuals with Jaberi-Elahi syndrome have been reported in the literature. This study, describes a review of the symptoms related to the Jaberi-Elahi syndrome. A large numbers of patients manifest motor development delay (26/28), sparse hair (26/28), and speech disorder (24/28). Moreover, a significant fraction of patients suffer from intellectual disability (23/28), hypotonia (23/28), skeletal problems (23/28), and visual impairment (18/28). In spite of previous patients, the proband in this study did not exhibit any skeletal abnormalities. In summary, we present evidence implicating a novel missense variant in Jaberi-Elahi syndrome, expanding and refining the genetic spectrum of this condition.

BACKGROUND: Self-determination is associated with lifelong positive outcomes. Students with intellectual disabilities typically have lower self-determination than their peers. Universal basic education access offers schools the opportunity to rectify this disparity. This is the first systematic review investigating the school-based practices that target self-determination development for students with intellectual disabilities.
METHODS: The review follows the PRISMA guidelines, spanning five databases (ProQuest databases, EMBASE, Scopus, Sage Journals, Taylor and Francis Online) from 2006 to 2021.
RESULTS: Across the 18 studies, the most used practice is the SDLMI. Research focuses on United States-based transition-aged students with mild to moderate intellectual disabilities. Social validity tends to be assessed in summative and informal ways. Students are not generally involved in decision-making about practices and individualisation of support.
CONCLUSIONS: Self-determination development for this population can begin before puberty. Future research should critically investigate social validity and holistic integration of student self-determination learning opportunities throughout the pedagogical cycle.

The NR4A2 gene encodes an orphan transcription factor of the steroid-thyroid hormone-retinoid receptor superfamily. This review focuses on the clinical findings associated with the pathogenic variants so far reported, including three unreported cases. Also, its role in neurodegenerative diseases, such as Parkinson\'s or Alzheimer\'s disease, is examined, as well as a brief exploration on recent proposals to develop novel therapies for these neurological diseases based on small molecules that could modulate NR4A2 transcriptional activity. The main characteristic shared by all patients is mild to severe developmental delay/intellectual disability. Moderate to severe disorder of the expressive and receptive language is present in at least 42%, while neuro-psychiatric issues were reported in 53% of patients. Movement disorders, including dystonia, chorea or ataxia, are described in 37% patients, although probably underestimated because of its frequent onset in late adolescence-young adulthood. Finally, epilepsy was surprisingly present in 42% of patients, being drug-resistant in three of them. The age at onset varied widely, from five months to twenty-six years, as did the classification of epilepsy, which ranged from focal epilepsy to infantile spasms or Lennox-Gastaut syndrome. Accordingly, we propose that NR4A2 should be considered as a first-tier target gene for the genetic diagnosis of developmental and epileptic encephalopathy.

Background: CACNA1C gene encodes the alpha 1 subunit of the CaV1.2 L-type Ca2+ channel. Pathogenic variants in this gene have been associated with cardiac rhythm disorders such as long QT syndrome, Brugada syndrome and Timothy syndrome. Recent evidence has suggested the possible association between CACNA1C mutations and neurologically-isolated (in absence of cardiac involvement) phenotypes in children, giving birth to a wider spectrum of CACNA1C-related clinical presentations. However, to date, little is known about the variety of both neurological and non-neurological signs/symptoms in the neurologically-predominant phenotypes. Methods and Results: We conducted a systematic review of neurologically-predominant presentations without cardiac conduction defects, associated with CACNA1C mutations. We also reported a novel de novo missense pathogenic variant in the CACNA1C gene of a children patient presenting with constructional, dressing and oro-buccal apraxia associated with behavioral abnormalities, mild intellectual disability, dental anomalies, gingival hyperplasia and mild musculoskeletal defects, without cardiac conduction defects. Conclusions: The present study highlights the importance of considering the investigation of the CACNA1C gene in children\'s neurological isolated syndromes, and expands the phenotype of the CACNA1C related conditions. In addition, the present study highlights that, even in absence of cardiac conduction defects, nuanced clinical manifestations of the Timothy syndrome (e.g., dental and gingival defects) could be found. These findings suggest the high variable expressivity of the CACNA1C gene and remark that the absence of cardiac involvement should not mislead the diagnosis of a CACNA1C related disorder.

SATB1 (MIM #602075) is a relatively new gene reported only in recent years in association with neurodevelopmental disorders characterized by variable facial dysmorphisms, global developmental delay, poor or absent speech, altered electroencephalogram (EEG), and brain abnormalities on imaging. To date about thirty variants in forty-four patients/children have been described, with a heterogeneous spectrum of clinical manifestations. In the present study, we describe a new patient affected by mild intellectual disability, speech disorder, and non-specific abnormalities on EEG and neuroimaging. Family studies identified a new de novo frameshift variant c.1818delG (p.(Gln606Hisfs*101)) in SATB1. To better define genotype-phenotype associations in the different types of reported SATB1 variants, we reviewed clinical data from our patient and from the literature and compared manifestations (epileptic activity, EEG abnormalities and abnormal brain imaging) due to missense variants versus those attributable to loss-of-function/premature termination variants. Our analyses showed that the latter variants are associated with less severe, non-specific clinical features when compared with the more severe phenotypes due to missense variants. These findings provide new insights into SATB1-related disorders.