Shared and divergent mental health characteristics of ADNP-, CHD8- and DYRK1A-related neurodevelopmental conditions.

BACKGROUND: Neurodevelopmental conditions such as intellectual disability (ID) and autism spectrum disorder (ASD) can stem from a broad array of inherited and de novo genetic differences, with marked physiological and behavioral impacts. We currently know little about the psychiatric phenotypes of rare genetic variants associated with ASD, despite heightened risk of psychiatric concerns in ASD more broadly. Understanding behavioral features of these variants can identify shared versus specific phenotypes across gene groups, facilitate mechanistic models, and provide prognostic insights to inform clinical practice. In this paper, we evaluate behavioral features within three gene groups associated with ID and ASD - ADNP, CHD8, and DYRK1A - with two aims: (1) characterize phenotypes across behavioral domains of anxiety, depression, ADHD, and challenging behavior; and (2) understand whether age and early developmental milestones are associated with later mental health outcomes. METHODS: Phenotypic data were obtained for youth with disruptive variants in ADNP, CHD8, or DYRK1A (N = 65, mean age = 8.7 years, 40% female) within a long-running, genetics-first study. Standardized caregiver-report measures of mental health features (anxiety, depression, attention-deficit/hyperactivity, oppositional behavior) and developmental history were extracted and analyzed for effects of gene group, age, and early developmental milestones on mental health features. RESULTS: Patterns of mental health features varied by group, with anxiety most prominent for CHD8, oppositional features overrepresented among ADNP, and attentional and depressive features most prominent for DYRK1A. For the full sample, age was positively associated with anxiety features, such that elevations in anxiety relative to same-age and same-sex peers may worsen with increasing age. Predictive utility of early developmental milestones was limited, with evidence of early language delays predicting greater difficulties across behavioral domains only for the CHD8 group. CONCLUSIONS: Despite shared associations with autism and intellectual disability, disruptive variants in ADNP, CHD8, and DYRK1A may yield variable psychiatric phenotypes among children and adolescents. With replication in larger samples over time, efforts such as these may contribute to improved clinical care for affected children and adolescents, allow for earlier identification of emerging mental health difficulties, and promote early intervention to alleviate concerns and improve quality of life.

Exploring an objective measure of overactivity in children with rare genetic syndromes.

BACKGROUND: Overactivity is prevalent in several rare genetic neurodevelopmental syndromes, including Smith-Magenis syndrome, Angelman syndrome, and tuberous sclerosis complex, although has been predominantly assessed using questionnaire techniques. Threats to the precision and validity of questionnaire data may undermine existing insights into this behaviour. Previous research indicates objective measures, namely actigraphy, can effectively differentiate non-overactive children from those with attention-deficit hyperactivity disorder. This study is the first to examine the sensitivity of actigraphy to overactivity across rare genetic syndromes associated with intellectual disability, through comparisons with typically-developing peers and questionnaire overactivity estimates. METHODS: A secondary analysis of actigraphy data and overactivity estimates from The Activity Questionnaire (TAQ) was conducted for children aged 4-15 years with Smith-Magenis syndrome (N=20), Angelman syndrome (N=26), tuberous sclerosis complex (N=16), and typically-developing children (N=61). Actigraphy data were summarized using the M10 non-parametric circadian rhythm variable, and 24-hour activity profiles were modelled via functional linear modelling. Associations between actigraphy data and TAQ overactivity estimates were explored. Differences in actigraphy-defined activity were also examined between syndrome and typically-developing groups, and between children with high and low TAQ overactivity scores within syndromes. RESULTS: M10 and TAQ overactivity scores were strongly positively correlated for children with Angelman syndrome and Smith-Magenis syndrome. M10 did not substantially differ between the syndrome and typically-developing groups. Higher early morning activity and lower evening activity was observed across all syndrome groups relative to typically-developing peers. High and low TAQ group comparisons revealed syndrome-specific profiles of overactivity, persisting throughout the day in Angelman syndrome, occurring during the early morning and early afternoon in Smith-Magenis syndrome, and manifesting briefly in the evening in tuberous sclerosis complex. DISCUSSION: These findings provide some support for the sensitivity of actigraphy to overactivity in children with rare genetic syndromes, and offer syndrome-specific temporal descriptions of overactivity. The findings advance existing descriptions of overactivity, provided by questionnaire techniques, in children with rare genetic syndromes and have implications for the measurement of overactivity. Future studies should examine the impact of syndrome-related characteristics on actigraphy-defined activity and overactivity estimates from actigraphy and questionnaire techniques.

Sleep quality relates to language impairment in children with autism spectrum disorder without intellectual disability.

OBJECTIVES: This study aimed to identify sleep quality profiles of children with autism spectrum disorder (ASD), to compare these profiles with those of typically developing (TD) children, and to verify whether there are differences between them in terms of language skills. METHODS: We evaluated the sleep quality and language skills of 47 children with ASD without intellectual disability (ID) and 32 children with TD. Using a hierarchical cluster analysis, we identified two sleep quality ASD profiles (poor and good). We then performed a series of MANCOVAs and ANOVAs to compare the sleep quality and language skills of the two ASD clusters and the TD group. RESULTS: A main group effect (TD, "poor" cluster, and "good" cluster) was found in the total sleep quality and all its dimensions. Significant differences were revealed between the "good" and "poor" clusters in the total structural language score (F1,46 = 10.75, p < 0.001) and three of its subscales (speech: F1,46 = 9.19, p < 0.001; syntax, F1,46 = 8.61, p = 0.001; coherence: F1,46 = 11.36, p < 0.001); the total pragmatic language score (F1,46 = 7.00, p = 0.001) and three of its subscales (inappropriate initiation: F1,46 = 8.02, p = 0.001; use of context: F1,46 = 8.07, p = 0.001; nonverbal communication: F1,46 = 7.35, p = 0.001); and the social relations score (F1,46 = 9.97, p = 0.003). CONCLUSIONS: Sleep quality in children with ASD (especially a subgroup) is worse than in children with TD. There is an association between sleep quality and language skills, both at the pragmatic and structural levels.

Definition, assessment and management of frailty for people with intellectual disabilities: A scoping review.

BACKGROUND: People with intellectual disabilities may experience frailty earlier than the general population. This scoping review aimed to investigate how frailty is defined, assessed, and managed in adults with an intellectual disability; factors associated with frailty; and the potential impact of COVID-19 on frailty identification and management. METHOD: Databases were searched from January 2016 to July 2023 for studies that investigated frailty in individuals with intellectual disabilities. RESULTS: Twenty studies met the inclusion criteria. Frailty prevalence varied between 9% and 84%. Greater severity of intellectual disability, presence of Down syndrome, older age, polypharmacy, and group home living were associated with frailty. Multiagency working, trusted relationships and provision of evidence-based information may all be beneficial in frailty management. CONCLUSION: Frailty is common for people with intellectual disabilities and is best identified with measures specifically designed for this population. Future research should evaluate interventions to manage frailty and improve lives.

Adherence to adhesive patch electrocardiographic monitoring among adults with disabilities.

BACKGROUND: Individuals with developmental and/or intellectual disabilities (I/DD) are at a greater risk for atrial fibrillation (AF), the most common type of cardiac arrhythmia. AF is associated with heart failure, stroke, poor mental health, and reduced quality of life. Management and treatment decisions are based on the ability to detect AF; however, noninvasive, remote cardiac monitoring may not be tolerated by individuals with I/DD. OBJECTIVE: To examine adherence to the placement of an ambulatory cardiac rhythm monitoring patch device by adult patients with I/DD. METHODS: Investigators extracted chart data from a consecutive series of adult patients (18 years+) who received the patch device as part of standard treatment at an adult health center between November 1, 2015 and October 31, 2019. RESULTS: A total of 95 patients were included in data analysis. Average age of subjects was 53.8 ± 13.9 years (range: 20.2-88.5); 66.7% were male. All subjects had intellectual disabilities as follows: mild, 37.9%; moderate, 29.5%; severe, 21.0%; and, profound, 11.6%. With a prescribed duration of 14 days, subjects wore the device a median (interquartile range [IQR]) of 12.2 days (4.1-14.0); total analysis time was a median of 9.5 days (3.4-13.5). A total of 29 subjects (30.5%) received cardiac diagnoses not previously identified (median = 1 new diagnosis; range: 1-5). CONCLUSIONS: This pilot study suggests the possible utility of an ambulatory monitoring patch device in an adult population with I/DD. Investigators recommend larger studies to confirm such preliminary findings to ultimately improve clinical management and patient quality of life.

Haploinsufficiency of ZFHX3, encoding a key player in neuronal development, causes syndromic intellectual disability.

Neurodevelopmental disorders (NDDs) result from impaired development and functioning of the brain. Here, we identify loss-of-function (LoF) variation in ZFHX3 as a cause for syndromic intellectual disability (ID). ZFHX3 is a zinc-finger homeodomain transcription factor involved in various biological processes, including cell differentiation and tumorigenesis. We describe 42 individuals with protein-truncating variants (PTVs) or (partial) deletions of ZFHX3, exhibiting variable intellectual disability and autism spectrum disorder, recurrent facial features, relative short stature, brachydactyly, and, rarely, cleft palate. ZFHX3 LoF associates with a specific methylation profile in whole blood extracted DNA. Nuclear abundance of ZFHX3 increases during human brain development and neuronal differentiation. ZFHX3 was found to interact with the chromatin remodeling BRG1/Brm-associated factor complex and the cleavage and polyadenylation complex, suggesting a function in chromatin remodeling and mRNA processing. Furthermore, ChIP-seq for ZFHX3 revealed that it predominantly binds promoters of genes involved in nervous system development. We conclude that loss-of-function variants in ZFHX3 are a cause of syndromic ID associating with a specific DNA methylation profile.

Racial and ethnic disparities in the co-occurrence of intellectual disability and autism: Impact of incorporating measures of adaptive functioning.

Intellectual disability (ID) commonly co-occurs in children with autism. Although diagnostic criteria for ID require impairments in both cognitive and adaptive functioning, most population-based estimates of the frequency of co-occurring ID in children with autism-including studies of racial and ethnic disparities in co-occurring autism and ID-base the definition of ID solely on cognitive scores. The goal of this analysis was to examine the effect of including both cognitive and adaptive behavior criteria on estimates of co-occurring ID in a well-characterized sample of 2- to 5-year-old children with autism. Participants included 3264 children with research or community diagnoses of autism enrolled in the population-based Study to Explore Early Development (SEED) phases 1-3. Based only on Mullen Scales of Early Learning (MSEL) composite cognitive scores, 62.9% (95% confidence interval [CI]: 61.1, 64.7%) of children with autism were estimated to have co-occurring ID. After incorporating Vineland Adaptive Behavior Scales, Second Edition (VABS-II) composite or domains criteria, co-occurring ID estimates were reduced to 38.0% (95% CI: 36.2, 39.8%) and 45.0% (95% CI: 43.1, 46.9%), respectively. The increased odds of meeting ID criteria observed for non-Hispanic (NH) Black and Hispanic children relative to NH White children when only MSEL criteria were used were substantially reduced, though not eliminated, after incorporating VABS-II criteria and adjusting for selected socioeconomic variables. This study provides evidence for the importance of considering adaptive behavior as well as socioeconomic disadvantage when describing racial and ethnic disparities in co-occurring ID in epidemiologic studies of autism.

Generation of two iPSC lines from Mowat-Wilson syndrome patients carrying heterozygous ZEB2 mutations.

ZEB2 is a protein-coding gene belonging to a very restricted family of transcription factors. ZEB2 acts mainly as a transcription repressor, is expressed in various tissues and its role is fundamental for the correct development of the nervous system. The best-known clinical picture associated with ZEB2 mutations is Mowat-Wilson syndrome, caused mostly by haploinsufficiency and characterized by possible multi-organ malformations, dysmorphic features, intellectual disability, and epilepsy. In this study we report the generation of IGGi004-A and IGGi005-A, iPSC clones from two patients carrying different heterozygous mutations in ZEB2, which can be used for disease modelling, pathophysiological studies and therapeutics testing.

Generation of a human induced pluripotent stem cell line (FDCHi012-A) from a patient with DYRK1A-related intellectual disability syndrome carrying DYRK1A mutation (c.1024G > T).

DYRK1A haploinsufficiency causes a neurodevelopmental syndrome termed DYRK1A-related intellectual disability syndrome which is associated with a range of symptoms including microcephaly, epileptic seizures, and autism spectrum disorder. Here, we generated an induced Pluripotent Stem Cell (iPSC) line with a de novo missense mutation (DYRKIA c.1024G > T) from the peripheral blood mononuclear cells of a patient with DYRK1A-related intellectual disability syndrome. This iPSC line showed normal karyotype, exhibited pluripotency, and has three embryonic germ layers differentiation capacity. This iPSC line will be of great use in investigating the disease mechanisms and drug screening for patients with DYRK1A-related intellectual disability syndrome.

Evaluating the Effectiveness of Take it Personal!+ in People With Mild Intellectual Disability or Borderline Intellectual Functioning and Substance Use Disorder: A Multiple Baseline Single-Case Experimental Study.

Individuals with mild intellectual disabilities or borderline intellectual functioning are at increased risk to develop a substance use disorder-however, effective treatment programs adapted to this target group are scarce. This study evaluated the effectiveness of Take it Personal!+ in individuals with mild intellectual disabilities or borderline intellectual functioning and substance use disorder. Take it Personal!+ is a personalized treatment based on motivational interviewing and cognitive-behavioral therapy supported by an mHealth application. Data were collected in a nonconcurrent multiple baseline single-case experimental design across individuals with four phases (i.e., baseline, treatment, posttreatment, and follow-up). Twelve participants were randomly allocated to baseline lengths varying between 7 and 11 days. Substance use quantity was assessed during baseline, treatment, and posttreatment with a daily survey using a mobile application. Visual analysis was supported with statistical analysis of the daily surveys by calculating three effect size measures in 10 participants (two participants were excluded from this analysis due to a compliance rate below 50%). Secondary, substance use severity was assessed with standardized questionnaires at baseline, posttreatment, and follow-up and analyzed by calculating the Reliable Change Index. Based on visual analysis of the daily surveys, 10 out of 12 participants showed a decrease in mean substance use quantity from baseline to treatment and, if posttreatment data were available, to posttreatment. Statistical analysis showed an effect of Take it Personal!+ in terms of a decrease in daily substance use in 8 of 10 participants from baseline to treatment and if posttreatment data were available, also to posttreatment. In addition, data of the standardized questionnaires showed a decrease in substance use severity in 8 of 12 participants. These results support the effectiveness of Take it Personal!+ in decreasing substance use in individuals with mild intellectual disabilities or borderline intellectual functioning.

Prevalence of swallowing difficulties and associated factors in older people with intellectual disabilities.

BACKGROUND: We investigated the prevalence of swallowing difficulties and associated factors in people with intellectual disability. METHODS: We included people aged 50+ receiving care for people with intellectual disabilities. The Dysphagia Disorder Survey (DDS) was used to assess swallowing difficulties. We determined the agreement between the DDS and swallowing difficulties in medical records. We used logistic regression analyses to explore associated factors. RESULTS: One thousand and fifty people were included. The prevalence of swallowing difficulties was 43.8%. Swallowing difficulties were not reported in the medical records of 83.3% of these cases. Frailty (odds ratio (OR) = 4.22, 95% CI = 2.05-8.71), mobility impairment (OR = 2.50, 95% CI = 1.01-6.19), and mealtime dependency (OR = 3.05, 95% CI = 1.10-8.47) were independently associated with swallowing difficulties. CONCLUSION: Swallowing difficulties are prevalent in older people with intellectual disability but may be under-recognised. Frailty may be a good indicator for population-based screening for swallowing difficulties.

A holistic approach to fragile X syndrome integrated guidance for person-centred care.

BACKGROUND: The Fragile X community has expressed a desire for centralised, national guidelines in the form of integrated guidance for Fragile X Syndrome (FXS). METHODS: This article draws on existing literature reviews, primary research and clinical trials on FXS, a Fragile X Society conference workshop and first-hand experience of clinicians who have worked with those living with FXS over many years. RESULTS: The article scopes proposed integrated guidance over the life course, including appendices of symptoms, comorbidities and referral options for FXS and Fragile X Premutation Associated Conditions. CONCLUSION: Integrated guidance would provide an authoritative source for doctors, health professionals, therapists, care workers, social workers, educators, employers, families and those living with FXS, so that a holistic, person-centred approach can be taken across the United Kingdom to garner the best outcomes for those with FXS.

Hao-Fountain syndrome: 32 novel patients reveal new insights into the clinical spectrum.

Hao-Fountain syndrome (HAFOUS, OMIM: #616863) is a neurodevelopmental disorder caused by pathogenic variants in the gene USP7 coding for USP7, a protein involved in several crucial cellular homeostatic mechanisms and the recently described MUST complex. The phenotype of HAFOUS is insufficiently understood, yet there is a great need to better understand the spectrum of disease, genotype-phenotype correlations, and disease trajectories. We now present a larger cohort of 32 additional individuals and provide further clinical information about six previously reported individuals. A questionnaire-based study was performed to characterize the phenotype of Hao-Fountain syndrome more clearly, to highlight new traits, and to better distinguish the disease from related neurodevelopmental disorders. In addition to confirming previously described features, we report hyperphagia and increased body weight in a subset of individuals. HAFOUS patients present an increased rate of birth complications, congenital anomalies, and abnormal pain thresholds. Speech impairment emerges as a potential hallmark of Hao-Fountain syndrome. Cognitive testing reports reveal borderline intellectual functioning on average, although some individuals score in the range of intellectual disability. Finally, we created a syndrome-specific severity score. This score neither indicates a sex- nor age-specific difference of clinical severity, yet highlights a more severe outcome when amino acid changes colocalize to the catalytic domain of the USP7 protein.

Remote delivery of a weight management intervention for adults with intellectual disabilities: Results from a randomized non-inferiority trial.

BACKGROUND: Remote delivery of multi-component weight management interventions results in clinically meaningful weight loss in adults without intellectual disabilities (ID), but the effectiveness of remotely delivered weight management interventions in adults with ID has not previously been evaluated. OBJECTIVE: To determine if a weight management intervention delivered remotely could achieve weight loss (kg) at 6 months that is non-inferior to in-person visits in adults with ID and overweight or obesity (BMI ≥25 kg/m2). METHODS: Participants were randomized to a 24-mo. trial (6 mos weight loss,12 mos weight maintenance, 6 mos. no-contact follow up) to compare weight loss achieved with the same multicomponent intervention delivered to individual participants in their home either remotely (RD) or during face-to-face home visits (FTF). RESULTS: One hundred twenty adults with ID (∼32 years of age, 53 % females) were randomized to the RD (n = 60) or the FTF arm (n = 60). Six-month weight loss in the RD arm (-4.9 ± 7.8 kg) was superior to 6-month weight loss achieved in the FTF arm (-2.1 ± 6.7 kg, p = 0.047). However, this may be partially attributed to the COVID-19 pandemic, since weight loss in the FTF arm was greater in participants who completed the intervention entirely pre-COVID (n = 33,-3.2 %) compared to post-COVID (n = 22, -0.61 %). Weight loss across did not differ significantly between intervention arms at 18 (p = 0.33) or 24 months (p = 0.34). CONCLUSION: Our results suggest that remote delivery is a viable option for achieving clinically relevant weight loss and maintenance in adults with ID. NCT REGISTRATION: NCT03291509.

Preferences and experiences of parents/guardians of youth with epilepsy and intellectual disability on reproductive health counseling.

OBJECTIVE: To explore the experiences and preferences of parents/guardians of adolescents and young adults (AYA) of childbearing potential with co-occurring epilepsy and intellectual disability (ID) regarding counseling by neurologists on sexual and reproductive health (SRH) topics such as pregnancy, contraception, menstruation, and folic acid supplementation. METHODS: We conducted semi-structured interviews with parents/guardians of AYAs (12-28 years old) of childbearing potential with co-occurring epilepsy and ID, recruited from a tertiary-care children's hospital. We confirmed the diagnoses of epilepsy and ID with the patient's neurologist and parent/guardian. All degrees of ID (e.g. mild/moderate/severe) were eligible. We audio-recorded and transcribed interviews. Two coders performed qualitative thematic analysis. RESULTS: Twenty-five parents/guardians completed interviews. Themes included: (1) Parents/guardians believe their child to be immune from sexual abuse due to their supervision, yet desire counseling about abuse recognition and prevention, which they also report not occurring (2) A common opinion was that counseling on menstruation was more relevant to their child's life than counseling about pregnancy-related topics (3) Parents/guardians reported a lack of counseling on pregnancy-related topics such as folic acid supplementation and teratogenesis and generally also reported some degree of interest in hearing about these topics from neurologists (4) Parents/guardians also reported a lack of counseling on drug interactions between contraception and ASMs, and were highly interested in learning more about this topic (5) Parents/guardians want neurologists to initiate annual comprehensive SRH counseling at puberty about most topics, but report that they often initiate SRH discussions themselves. CONCLUSION: Parents/guardians of AYAs with epilepsy and ID prefer more frequent, neurologist-initiated, comprehensive conversations surrounding SRH particularly emphasizing menstruation and sexual abuse recognition/prevention. Findings may inform professional and patient education and health systems interventions including development of discussion guides and/or decision aides to improve SRH care for AYAs with epilepsy and ID.

Posterior Hypothalamic Region Deep Brain Stimulation for the Treatment of Aggression Disorders in Patients with Intellectual Disability: A Systematic Review.

INTRODUCTION: Aggressive disorders, in patients with intellectual disability, are satisfactorily managed with an educational, psychological, and pharmacological approach. Posterior hypothalamic region deep brain stimulation emerged in the last two decades as a promising treatment for patients with severe aggressive disorders. However, limited experiences are reported in the literature. METHODS: A systematic review was performed following PRISMA guidelines and recommendations by querying PubMed and Embase on August 24th, 2022, with the ensuing string parameters: ([deep brain stimulation] OR [DBS]) AND ([aggressiv*] OR disruptive). Cochrane Library, DynaMed, and ClinicalTrials.gov were consulted using the combination of keywords "deep brain stimulation" and "aggressive" or "aggression". The clinical outcome at the last follow-up and the rate of complications were considered primary and secondary outcomes of interest. RESULTS: The initial search identified 1,080 records, but only 10 studies met the inclusion criteria and were considered. The analysis of clinical outcome and complications was therefore performed on a total of 60 patients. Quality of all selected studies was classified as high, but one. Mean Overt Aggression Scale (OAS) improvement was 68%, while Inventory for Client Agency Planning (ICAP) improvement ranged between 38.3% and 80%. Complications occurred in 4 patients (6.7%). CONCLUSION: Posterior hypothalamic region deep brain stimulation may be considered a valuable option for patients with severe aggression disorders and ID. This review can represent a mainstay for those who will be engaged in the surgical treatment of these patients.

Unilateral progressive anterior iris adhesions in Mowat-Wilson syndrome: a new ocular finding.

Ocular associations in Mowat-Wilson syndrome (MWS) are rare. Those involving the anterior segment are scarce in the literature. We describe a child with genetic confirmation of MWS that presented with acquired onset of unilateral anterior iris adhesions with no known trauma.

Evaluation of RURS elbow guard in the management of thumb-sucking habit in children with and without intellectual disability.

BACKGROUND: Digit sucking is a common oral habit among many children, which involves placing the thumb/finger into the mouth, which can cause malocclusion in mixed and permanent dentition. AIM: To evaluate the efficacy of the RURS elbow guard in the management of thumb-sucking habits in children with intellectual disabilities and those without in terms of the mean duration of appliance therapy. The secondary objective was to compare the RURS elbow guard with an intraoral crib in healthy children (without intellectual disabilities) to manage the habit of thumb-sucking. DESIGN: Children with intellectual disabilities and those without between the age of 4 and 16 years were included in the study and categorised into three groups, namely group I (50 normal children; intraoral crib appliance), group II (50 normal children; RURS elbow guard) and group III (50 children with intellectual disabilities; RURS elbow guard). RESULTS: The mean duration of appliance therapy for groups I, II and III were 200.20 ± 20.43 days, 204.34 ± 20.56 days, and 218.43 ± 15.66 days, respectively (p < 0.001). The differences in the mean duration between group I and group II were statistically non-significant, with statistically significant differences between group I and group III (p < 0.001) and between group II and group III (p < 0.05). CONCLUSION: The RURS elbow guard was found to be an efficient appliance in treating thumb-sucking among children who had mild to moderate intellectual disabilities. RURS elbow guard was equally efficient as an intraoral crib appliance in managing thumb-sucking habits in children without intellectual disabilities.

Differences in Telemedicine Use Between People With and Without an Intellectual or Other Developmental Disability During the COVID-19 Pandemic.

Telemedicine utilization of people with an Intellectual or Other Developmental Disability (IDD) during the COVID-19 Pandemic is not well known. This study compares telemedicine utilization of those with and without IDD prior to the pandemic to after it began. Using the Utah All Payers Claims Database from 2019 to 2021, the study identified telemedicine utilization of adults aged 18 to 62 years old in 2019. Propensity score matching was used to minimize observed confounders of subjects with and without IDD in 2019. Negative binomial regression was used to identify factors that were associated with telemedicine utilization. The final number of subjects in the analysis was 18 204 (IDD: n = 6068, non-IDD: n = 12 136 based on 1:2 propensity score matching). The average (SD) age of the subjects was 31 (11.3) years old in 2019. Forty percent of the subjects were female, about 70% of subjects were covered by Medicaid in 2019. Average (SD) number of telemedicine use in 2020 (IDD: 1.96 (5.97), non-IDD: 1.18 (4.90); P < .01) and 2021 (IDD: 2.24 (6.78) vs 1.37 (5.13); P < .01) were higher for the IDD group than the non-IDD group. The regression results showed that the subjects with IDD had 56% more telemedicine encounters than those in the non-IDD group (Incidence Rate Ratio (IRR) = 1.56, P < .01). The growth of telemedicine during the COVID-19 pandemic has the potential to reduce persistent healthcare disparities in individuals with IDD. However, quality of telemedicine should be considered when it is provided to improve health of subjects with IDD.

Gatad2b, associated with the neurodevelopmental syndrome GAND, plays a critical role in neurodevelopment and cortical patterning.

GATAD2B (GATA zinc finger domain containing 2B) variants are associated with the neurodevelopmental syndrome GAND, characterized by intellectual disability (ID), infantile hypotonia, apraxia of speech, epilepsy, macrocephaly and distinct facial features. GATAD2B encodes for a subunit of the Nucleosome Remodeling and Histone Deacetylase (NuRD) complex. NuRD controls transcriptional programs critical for proper neurodevelopment by coupling histone deacetylase with ATP-dependent chromatin remodeling activity. To study mechanisms of pathogenesis for GAND, we characterized a mouse model harboring an inactivating mutation in Gatad2b. Homozygous Gatad2b mutants die perinatally, while haploinsufficient Gatad2b mice exhibit behavioral abnormalities resembling the clinical features of GAND patients. We also observed abnormal cortical patterning, and cellular proportions and cell-specific alterations in the developmental transcriptome in these mice. scRNAseq of embryonic cortex indicated misexpression of genes key for corticogenesis and associated with neurodevelopmental syndromes such as Bcl11b, Nfia and H3f3b and Sox5. These data suggest a crucial role for Gatad2b in brain development.