Assessment Of Autism Spectrum Disorder Research Articles

Adults with autism spectrum disorder and the criminal justice system: An investigation of prevalence of contact with the criminal justice system, risk factors and sex differences in a specialist assessment service.

The behavioural and cognitive difficulties of some adults with autism spectrum disorder (ASD) may increase their risk of contact with the criminal justice system (CJS) as a potential suspect. There has been limited investigation of ASD and offending and available evidence is mixed. A retrospective review was completed of medical records of 1570 adults (17–75 years old) who were referred for an ASD assessment over a 17-year period (April 2003 to February 2020). Of the adults diagnosed with ASD, 23% had previous contact with the CJS. Being male or diagnosed with co-occurring attention-deficit hyperactivity disorder (ADHD) and/or psychotic disorder were risk factors for CJS contact. However, the rates of contact with the CJS or for specific offences in the ASD group were never higher than adults referred to our service but not diagnosed with ASD. We did not include a general population comparison group, therefore cannot say how rates of CJS contact in ASD compare with the general population. Further health services research for adults with ASD is warranted, as modifying the treatable risk factors (i.e. ADHD) could reduce contact with the CJS. In addition, joint working between CJS and mental health services could reduce the risk of adults with ASD having CJS contact.Lay abstractThere has been growing interest in offending and contact with the criminal justice system (CJS) by people with autism spectrum disorder (ASD). However, it is not clear whether people with ASD offend more than those without ASD. Studies have started to look at whether there are particular offences people with ASD are more likely to commit and whether there are any factors that can affect whether someone comes into contact with the CJS as a potential suspect. This study looked at the patients who attended an ASD diagnostic service over a 17-year period to see the rate of contact with the CJS of those who were diagnosed with ASD and whether there were any particular factors that might increase the risk of CJS contact. Nearly a quarter of the ASD group had some contact with the CJS as a potential suspect. Factors that seemed to increase whether someone with ASD was more likely to have contact with the CJS were being male, being diagnosed with ADHD, and being diagnosed with psychosis. This study is one of the largest studies to investigate the rate of CJS contact as a potential suspect in a sample of adults with ASD in an attempt to give a clearer picture of what might influence someone with ASD to engage in offending behaviour in order to try to see what mental health services can offer to reduce the likelihood of someone with ASD coming into contact with the CJS, for example, treatment for another condition or support.

Understanding Caregiver Satisfaction With a Telediagnostic Assessment of Autism Spectrum Disorder.

In light of the COVID-19 pandemic, it is critical to understand the feasibility and acceptability of the use of telediagnostic assessments in clinical settings. This study aimed to characterize caregiver satisfaction with a telediagnostic assessment of autism spectrum disorder (ASD). Twelve families completed a telediagnostic assessment of ASD through Illinois' Early Intervention program including a caregiver interview, administration of the TELE-ASD-PEDS, and a feedback visit. Following the evaluation, caregivers rated their satisfaction with the telediagnostic assessment. Caregivers reported that the evaluation met their expectations, and they were satisfied with the assessment and feedback visit. However, caregiver satisfaction with the telehealth platform varied, and the majority of caregivers reported a preference for in-person visits. Qualitative analysis of caregiver responses noted the benefits and areas of improvement of telediagnostic assessment. Thematic analysis revealed the strengths of the telediagnostic assessment, including the logistical convenience of the teleassessment, ease of administration, rapport with and expertise of the clinicians, and qualification for intervention services. Although caregivers' perspectives varied, diagnostic accuracy and the amount of information provided about the diagnosis were reported areas of improvement. Overall, telediagnostic assessments were well received by families. Caregivers' preference for in-person visits highlights the need to incorporate caregiver-reported areas of improvement in the development and administration of telediagnostic assessments.

A semi-supervised autoencoder for autism disease diagnosis

Autism spectrum disorder (ASD) is a neurological developmental disorder that typically causes impaired communication and compromised social interactions. The current clinical assessment of ASD is typically based on behavioral observations and lack of the understanding of the neurological mechanism and the progression of the brain development. The functional magnetic resonance imaging (fMRI) data is one of the commonly-used imaging modalities for understanding human brain mechanisms as well as the diagnosis and treatment of brain disorders such as ASD. In this paper, we proposed a semi-supervised autoencoder (AE) for autism diagnosis using functional connectivity (FC) pattern obtained from resting-state fMRI. An unsupervised autoencoder in combination with the supervised classification networks enables semi-supervised learning in which an autoencoder for learning hidden features and a neural network based classifier are trained together. Compared to train the autoencoder and classifier in separate phases, the proposed semi-supervised learning essentially helps tune the latent feature representation learning towards the goal of classification, and thus leads to improvements in autism diagnosis performance. The proposed model is evaluated by using cross-validation methods on ABIDE I database. Experimental results demonstrate that the proposed model achieves improved classification performance, and that the proposed semi-supervised learning framework can integrate unlabelled fMRI data for better feature learning and improved classification accuracy.

Clinician Perspectives on Telehealth Assessment of Autism Spectrum Disorder During the COVID-19 Pandemic.

This study examined clinician insights into telehealth assessment services for autism spectrum disorder implemented during the COVID-19 pandemic. 35 clinicians from multiple disciplines across 17 sites in the Autism Care Network were interviewed. Themes identified through qualitative analyses included factors related to confidence in diagnosis (impressions of in-home observation; child and family factors that affected diagnostic confidence; changes in rapport); patient and family factors related to telehealth (perceived family benefits of and barriers to telehealth; factors related to healthcare disparities; factors specific to non-native English speakers); and institutional and workplace factors related to transitioning to telehealth (institutional support; changes to efficacy, attendance, and work satisfaction). Results suggest that telehealth has potential to be an effective tool in autism assessment practice.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10803-022-05435-z.

Identifying Patient Characteristics to Understand Which Children May Receive Diagnostic Clarity in a Virtual Autism Spectrum Disorder Evaluation.

Given long waitlists for autism spectrum disorder (ASD) evaluation coupled with the COVID-19 pandemic, it is crucial to triage patients to services they are likely to receive diagnostic clarity (i.e., virtual, in-person evaluation). Participants attended a virtual ASD assessment. A subset also attended in-person evaluation. Results suggest younger children with educational services for ASD may benefit from virtual assessment while older patients with a history of psychiatric conditions may benefit from in-person evaluation. An ASD symptom severity tool related to virtual and in-person diagnostic clarity. Family history of ASD related to in-person diagnosis while other variables (e.g., age, educational services) did not. The study suggests patient characteristics may be used to determine for whom virtual ASD assessment may be appropriate.

Autism Assessment in Low- and Middle-Income Countries: Feasibility and Usability of Western Tools

The research on autism spectrum disorder (ASD) disproportionately originates from high-income countries, indicating a disparity of research in low- and middle-income countries (LMIC). One possible reason for this disparity is a lack of culturally appropriate screening and diagnostic tools for use in LMIC. Although a number of tools are commonly used in the United States, it is likely that using these tools in contexts in which they were not intended may be problematic. As such, this study examined factors that may inhibit the feasibility and usability of common ASD assessment tools in LMIC. Assessments were analyzed for readability, initial and continued cost, training required, restrictions on purchasing, materials required, and presence of items assessing expressive and receptive language. Results of the study indicated that the majority of validated ASD assessment tools present a multitude of barriers for use in LMIC. Implications for research and practice are discussed.

Development of a visual attention based decision support system for autism spectrum disorder screening

Visual attention of young children with autism spectrum disorder (ASD) has been well documented in the literature for the past 20 years. In this study, we developed a Decision Support System (DSS) that uses machine learning (ML) techniques to identify young children with ASD from typically developing (TD) children. Study participants included 26 to 36 months old young children with ASD (n = 61) and TD children (n = 72). The results showed that the proposed DSS achieved up to 87.5% success rate in the early assessment of ASD in young children. Findings suggested that visual attention is a unique, promising biomarker for early assessment of ASD. Study results were discussed, and suggestions for future research were provided.

Screening for autism spectrum disorder in deaf adults with intellectual disability: Feasibility and accuracy of two autism screening instruments

Abstract backgroundThere is a lack of autism screening instruments for deaf or hard of hearing (DHH) adults with intellectual disability. AimsThis study examined the diagnostic validity of the Pervasive Developmental Disorder in Mental Retardation Scale and the Diagnostic Behavioral Assessment for autism spectrum disorder – Revised in this rare population. Methods and participants56 DHH adults with intellectual disability living in three specialized therapeutic communities were examined, 9 of whom met criteria for autism. Outcomes and resultsWith minimal adaptions regarding item interpretation, both tools showed good diagnostic and high convergent validity. Items probing for difficulties in reciprocal social interaction and restricted interests were discriminant between individuals with and without autism. ConclusionThese data suggest that both autism screening tools are feasible and psychometrically sound when used with appropriate adaptations for DHH adults with intellectual disability.

Effectiveness of Screening in Early Intervention Settings to Improve Diagnosis of Autism and Reduce Health Disparities

The American Academy of Pediatrics recommends referring children at elevated risk of autism spectrum disorder (ASD) for Part C early intervention (EI) services, but notes that EI services often fail to provide ASD screening. To evaluate the hypothesis that a multistage screening protocol for ASD implemented in 3 EI settings will increase autism detection, especially among Spanish-speaking families. Difference-in-differences analyses with propensity score weighting of a quasi-experimental design using administrative data on 3 implementation EI agencies and 9 comparison EI agencies from 2012 to 2018 provided by the Massachusetts Department of Public Health. Eligible children were aged 14 to 36 months, enrolled in EI, had no prior ASD diagnosis or medical condition precluding participation, and had parents who spoke English or Spanish. The final analytic sample included 33 326 unique patients assessed across 150 200 person-quarters. Multistage ASD assessment protocol including ASD screening questionnaires, observational screener, and diagnostic evaluation. Increased incidence of ASD diagnoses as documented in Department of Public Health records and reductions in language-associated health care disparities. Implementation of screening at 3 EI sites was associated with a significant increase in the rate of ASD diagnoses (incidence rate ratios [IRR], 1.6; 95% CI, 1.3-2.1; P < .001), representing an additional 8.1 diagnoses per 1000 children per quarter. Among Spanish-speaking families, screening was also associated with a significant increase in the rate of ASD diagnoses (IRR, 2.6; 95% CI, 1.6-4.3; P < .001), representing 15.4 additional diagnoses per 1000 children per quarter-a larger increase than for non-Spanish-speaking families (interaction IRR, 1.8; 95% CI, 1.0-3.1; P = .005). Exploratory analyses revealed that screening was associated with a larger increase in the rate of ASD diagnoses among boys (IRR, 1.8; 95% CI, 1.4-2.3; P < .001) than among girls (IRR, 1.1; 95% CI, 0.6-1.7; P = .84). In this study, associations between increased rates of ASD diagnoses and reductions in disparities for Spanish-speaking households support the effectiveness of multistage screening in EI. This study provides a comprehensive evaluation of ASD screening in EI settings as well as a rigorous evaluation of ASD screening in any setting with a no-screening comparison condition. Given that the intervention included multiple components, mechanisms of action warrant further research, as do disparities by child sex.

Development and initial testing of the BABY-BISCUIT in an at-risk population

ABSTRACT Purpose: Early identification of autism spectrum disorder (ASD) via screeners for diagnostic measures are a high priority. At present, there is no consensus on one screener due to the need for better sensitivity and specificity. In this study, we report on the development and utility of the BABY-BISCUIT, a six-item screener based on a modified subset of items from the Baby and Infant Screen for Children with aUtIsm Traits (BISCUIT). Methods: A sample of 504 children between 17–3 9months of age, who consisted of toddlers identified as at-risk for neurodevelopmental and other health disorders, were tested during an annual screening through the Louisiana EarlySteps program. Results: An exploratory factor analysis yielded a one-factor solution (X2 = 48.62, df = 9, p = <.001). High sensitivity (i.e., 100.0%) at the cost of reduced specificity (i.e., 33.3%, AUC = 0.957) was found for an optimal screening cutoff score of 1. Conclusions: Findings from this study suggest that the BABY-BISCUIT has the potential to be a short and easily administered screener for ASD to inform whether further ASD assessment is necessary. Further investigation of convergent validity with established ASD measures is recommended.

Toward a cumulative science of vocal markers of autism: A cross-linguistic meta-analysis-based investigation of acoustic markers in American and Danish autistic children.

Acoustic atypicalities in speech production are argued to be potential markers of clinical features in autism spectrum disorder (ASD). A recent meta-analysis highlighted shortcomings in the field, in particular small sample sizes and study heterogeneity. We showcase a cumulative (i.e., explicitly building on previous studies both conceptually and statistically) yet self-correcting (i.e., critically assessing the impact of cumulative statistical techniques) approach to prosody in ASD to overcome these issues. We relied on the recommendations contained in the meta-analysis to build and analyze a cross-linguistic corpus of multiple speech productions in 77 autistic and 72 neurotypical children and adolescents (>1000 recordings in Danish and US English). We used meta-analytically informed and skeptical priors, with informed priors leading to more generalizable inference. We replicated findings of a minimal cross-linguistically reliable distinctive acoustic profile for ASD (higher pitch and longer pauses) with moderate effect sizes. We identified novel reliable differences between the two groups for normalized amplitude quotient, maxima dispersion quotient, and creakiness. However, the differences were small, and there is likely no one acoustic profile characterizing all autistic individuals. We identified reliable relations of acoustic features with individual differences (age, gender), and clinical features (speech rate and ADOS sub-scores). Besides cumulatively building our understanding of acoustic atypicalities in ASD, the study shows how to use systematic reviews and meta-analyses to guide the design and analysis of follow-up studies. We indicate future directions: larger and more diverse cross-linguistic datasets, focus on heterogeneity, self-critical cumulative approaches, and open science. LAY SUMMARY: Autistic individuals are reported to speak in distinctive ways. Distinctive vocal production can affect social interactions and social development and could represent a noninvasive way to support the assessment of autism spectrum disorder (ASD). We systematically checked whether acoustic atypicalities highlighted in previous articles could be actually found across multiple recordings and two languages. We find a minimal acoustic profile of ASD: higher pitch, longer pauses, increased hoarseness and creakiness of the voice. However, there is much individual variability (by age, sex, language, and clinical characteristics). This suggests that the search for one common "autistic voice" might be naive and more fine-grained approaches are needed.

Exploring the Experience of Seeking an Autism Diagnosis as an Adult.

Emerging research suggests that seeking an autism diagnosis as an adult is usually difficult and time-consuming but brings relief once a diagnosis is made. This study explored the experience of the pathway to an autism diagnosis during adulthood for adults living in Australia. We conducted a qualitative phenomenological study and interviewed 13 adults who identified as autistic about their pathway to autism diagnosis in their mode of choice. Spoken interviews were transcribed verbatim, and transcripts were analyzed by using a thematic approach. Data analysis resulted in 6 themes and 20 meaning units that described the experiences of adults seeking an autism diagnosis in Australia. These themes involved two interwoven journeys that spanned before, during, and after the diagnostic process. The personal journey involved feeling different, considering autism, and living as autistic, whereas the clinical journey involved missed opportunities, varied diagnostic experiences, and absent supports. Given the potential benefits for adults obtaining a formal autism diagnosis and accessing post-diagnostic supports, it is important that health professionals and governments collaborate to reduce access barriers and ensure adequate services are available. The findings from this study informed the development of Australia's national guideline for autism diagnosis.

Accuracy of Three Screening Instruments in Identifying Preschool Children at Risk for Autism Spectrum Disorder

An efficient approach for screening and identifying children at risk for autism spectrum disorder (ASD) remains a pressing need. The aim of this exploratory study was to examine the ability of two general developmental screening tests to identify children at risk for ASD. We compared the accuracy of one general developmental screening instrument, Ages and Stages Questionnaires (ASQ), and one general social emotional screening instrument, the Ages and Stages Questionnaire: Social Emotional (ASQ:SE), with the Social Communication Questionnaire (SCQ), an ASD-specific screening instrument. Two hundred eight children between 36 and 66 months were recruited through 19 community ASD programs, websites, and magazines. The three screening instruments were given to 285 parent/child dyads with and without a diagnosis of ASD, online via a screening website linked to a university. Sixty-four children had been diagnosed with ASD and were receiving special education services (e.g., behavioral interventions) prior to their participation. The classification agreement of the ASQ (i.e., sensitivity = 84.38%, specificity = 81.45%) outperformed the other two screening instruments; classification agreement of the SCQ was sensitivity = 70.31% and specificity = 87.33%; and of the ASQ: SE, sensitivity = 82.81% and specificity = 72.40%. Agreement among the questionnaires ranged from moderate to strong as measured by Pearson Product Moment Correlation Coefficients. Children diagnosed with ASD had scores below the screening cutoff points, indicating risk, most often on three ASQ domains: (a) communication, (b) gross motor, and (c) personal social. This exploratory study indicated the feasibility of using the ASQ in screening clinics for finding children at risk for ASD, if the ASQ is followed by specific ASD assessments. Design limitations, including a sample of children with ASD already receiving intervention services may explain the somewhat lower sensitivity of the SCQ.

Building Capacity for Community Pediatric Autism Diagnosis: A Systemic Review of Physician Training Programs.

Training primary care providers to provide diagnostic assessments for autism spectrum disorder (ASD) decreases wait times and improves diagnostic access. Outcomes related to the quality of these assessments and the impacts on system capacity have not been systematically examined. This systematic review identifies and summarizes published studies that included ASD diagnostic training for primary care providers (PCPs) and aims to guide future training and evaluation methods. Systematic searches of electronic databases, reference lists, and journals identified 6 studies that met 3 inclusion criteria: training for PCPs, community setting, and training outcome(s) reported. These studies were critically reviewed to characterize (1) study design, (2) training model, and (3) outcomes. All studies were either pre-post design or nonrandomized trials with a relatively small number of participants. There was considerable heterogeneity among studies regarding the training provided and the program evaluation process. The most evaluated outcomes were access to autism diagnosis and accuracy of diagnosis. Training PCPs to make ASD diagnoses can yield high diagnostic agreement with specialty teams' assessments and reduce diagnostic wait times. Current data are limited by small sample size, poor to fair quality study methodology, and heterogenous study designs and outcome evaluations. Evidence is insufficient to draw conclusions about the overall effects of training PCPs for ASD diagnostic assessments. Since further research is still needed, this review highlights which outcomes are relevant to consider when evaluating the quality of ASD assessments across the continuum of approaches.

Magnetic resonance spectroscopy features of the thalamus and the cerebellum and their association with clinical features in children with autism spectrum disorder: a prospective study.

To study the changes in biochemical metabolites in the thalamus and the cerebellum and their association with clinical features in children with autism spectrum disorder (ASD). In this prospective study, magnetic resonance spectroscopy (MRS) with point-resolved spatial selection was used to analyze the thalamus and the cerebellum at both sides in 50 children with ASD aged 2-6 years. Creatine (Cr) was as the internal standard to measure the relative values of N-acetylaspartate (NAA)/Cr, choline (Cho)/Cr, myoinositol (MI)/Cr, and glutamine and glutamate complex (Glx)/Cr, and the differences in metabolites and their association with clinical symptoms were compared. In the children with ASD, NAA/Cr in the left thalamus was positively correlated with the scores of hearing-language and hand-eye coordination in the Griffiths Development Scales-Chinese (P<0.05). Cho/Cr in the right cerebellum was positively correlated with the scores of personal-social competence, hearing-language, and hand-eye coordination (P<0.05). NAA/Cr and Glx/Cr in the left thalamus were positively correlated with those in the left cerebellum (P<0.05). There was no significant difference in metabolites between the left and right sides of the thalamus and the cerebellum in the children with ASD (P>0.05). There are metabolic disorders in the cerebellum and the thalamus in children with ASD, and there is a correlation between the changes of metabolites in the left cerebellum and the left thalamus. Some metabolic indexes are related to the clinical symptoms of ASD. MRS may reveal the pathological basis of ASD and provide a basis for diagnosis and prognosis assessment of ASD as a noninvasive and quantitative detection method.

Autism spectrum disorder in a rural community in Bangladesh: A mid-childhood assessment.

Population-based studies employing standardized diagnostics are needed to determine the burden of autism spectrum disorder (ASD) in low-resource settings. A community-based study was conducted among 8-11 year old children in rural, northwestern Bangladesh to establish the prevalence of ASD. A standardized screening and diagnosis protocol was adapted and deployed comprising the social communication questionnaire (SCQ), and the autism diagnostic observation schedule 2, (ADOS-2), and the autism diagnostic interview, revised (ADI-R), respectively. A year-long research training was conducted for a clinical psychologist to be certified to administer ADOS-2 and ADI-R. Over 8000 children were visited at home and administered the SCQ leading to some, based on their score, being further evaluated using the ADOS-2 and ADI-R by the clinical psychologist. Based on ADOS-2 applying the diagnoses of autism or autism spectrum, the prevalence was 40 (95% CI: 27, 54) per 10,000. Autistic disorder using ADI-R was found at 12 (95% CI: 5, 20) per 10,000. Boys were at a higher risk than girls with the rates among boys being 46 (95% CI: 25, 67) using ADOS-2 and 19 (95% CI:6, 33) using ADI-R. Among girls the rates were 34 (95% CI:16, 52) and 5 (95% CI:0, 12) per 10,000, respectively. Challenges to undertaking ASD research in a rural South Asian context are discussed. There was a low-to-moderate prevalence of ASD in a rural, child population in Bangladesh. Future research is needed to estimate rates of ASD and its causes and socioeconomic consequences in rural and urban settings of South Asia. LAY SUMMARY: In a study of over 8000, 8-11 year old children in a rural area of Bangladesh, two to four out of 1000 had ASD. Boys more than girls had ASD. Conducting ASD assessment in this setting was difficult, but more such research is needed to understand what causes ASD and its consequences for the individual, families and the society in rural and urban areas of low-income countries.

The Contribution of Machine Learning and Eye-Tracking Technology in Autism Spectrum Disorder Research: A Systematic Review

Early and objective autism spectrum disorder (ASD) assessment, as well as early intervention are particularly important and may have long term benefits in the lives of ASD people. ASD assessment relies on subjective rather on objective criteria, whereas advances in research point to up-to-date procedures for early ASD assessment comprising eye-tracking technology, machine learning, as well as other assessment tools. This systematic review, the first to our knowledge of its kind, provides a comprehensive discussion of 30 studies irrespective of the stimuli/tasks and dataset used, the algorithms applied, the eye-tracking tools utilised and their goals. Evidence indicates that the combination of machine learning and eye-tracking technology could be considered a promising tool in autism research regarding early and objective diagnosis. Limitations and suggestions for future research are also presented.

Eye gaze as a biomarker in the recognition of autism spectrum disorder using virtual reality and machine learning: A proof of concept for diagnosis.

The core symptoms of autism spectrum disorder (ASD) mainly relate to social communication and interactions. ASD assessment involves expert observations in neutral settings, which introduces limitations and biases related to lack of objectivity and does not capture performance in real-world settings. To overcome these limitations, advances in technologies (e.g., virtual reality) and sensors (e.g., eye-tracking tools) have been used to create realistic simulated environments and track eye movements, enriching assessments with more objective data than can be obtained via traditional measures. This study aimed to distinguish between autistic and typically developing children using visual attention behaviors through an eye-tracking paradigm in a virtual environment as a measure of attunement to and extraction of socially relevant information. The 55 children participated. Autistic children presented a higher number of frames, both overall and per scenario, and showed higher visual preferences for adults over children, as well as specific preferences for adults' rather than children's faces on which looked more at bodies. A set of multivariate supervised machine learning models were developed using recursive feature selection to recognize ASD based on extracted eye gaze features. The models achieved up to 86% accuracy (sensitivity=91%) in recognizing autistic children. Our results should be taken as preliminary due to the relatively small sample size and the lack of an external replication dataset. However, to our knowledge, this constitutes a first proof of concept in the combined use of virtual reality, eye-tracking tools, and machine learning for ASD recognition. LAY SUMMARY: Core symptoms in children with ASD involve social communication and interaction. ASD assessment includes expert observations in neutral settings, which show limitations and biases related to lack of objectivity and do not capture performance in real settings. To overcome these limitations, this work aimed to distinguish between autistic and typically developing children in visual attention behaviors through an eye-tracking paradigm in a virtual environment as a measure of attunement to, and extraction of, socially relevant information.

Neurodevelopmental Screening in Young Children with Sickle Cell Disease

It is important to prioritize screening and surveillance for neurodevelopmental dysfunction in children with SCD because this vulnerable population is at higher risk for neurological complications including stroke, silent cerebral infarction, and neurodevelopmental disorders (NDD) such as language disorders, attention deficit hyperactivity disorder, and autism spectrum disorder (ASD). The American Society of Hematology (ASH) and American Academy of Pediatrics (AAP) have published guidelines to accomplish this, as well as to improve quality of life for people with SCD and NDDs. Despite the recognition of the increased risk and the clinical guidelines, the co-occurrence rates of SCD and NDD remain lower than expected.We hypothesize that the risk of NDDs is lower than expected in children with SCD due to low rates of neurodevelopmental screening and surveillance among primary care providers and hematologists, particularly in young children. Therefore, we examined the frequency of neurodevelopmental screening and surveillance among young children with SCD and identified clinical characteristics of young children with SCD who did not receive appropriate neurodevelopmental screening and surveillance.We conducted a retrospective chart review using the clinic rosters of two affiliated inner-city hospitals with a pediatric hematology clinic and sickle cell neurodevelopmental clinic. Children under 5 years old with SCD confirmed by their hematologists who were not adopted or in foster care were included in the study. A total of 276 patients were identified and reviewed. NDD and ASD specific screenings were documented at the time of review, although participants may have been diagnosed later in life. Analyses were completed using chi squared test, Fisher exact test, t-test in Stata IC-15.Patients were screened by a variety of providers, most commonly pediatricians and hematologists (see Figure 1). Table 1a shows the characteristics of the SCD patients assessed/not assessed for appropriate neurodevelopment (ND) by their pediatrician and/or hematologist. A total of 214 participants qualified for study inclusion and 148 participants (70%) were assessed for neurodevelopment. Ages and Stages Questionnaire- 3 (32%) and other non-standardized screening tools (85%) were the most common tool used (see Table 2a). Of the ND assessed patients (N=148), 37 (25%) were diagnosed with NDDs (see Table 3a). Among the not assessed ND patients (N=66), 16 (24%) were diagnosed with NDDs. Table 1b shows the characteristics of the SCD patients assessed/not assessed specifically for ASD by their pediatrician and/or hematologist. A total of 207 participants qualified for study inclusion and 39 participants (19%) were assessed for ASD. Modified Checklist for Autism in Toddlers (92%) was the most utilized screening tool (see Table 2b). None of these patients had ASD. Of the ASD assessed patients (N=39), 9 (23%) were diagnosed with NDDs (see Table 3a). Among the not assessed ASD patients (N=168), 41 (24%) were diagnosed with NDDs.Children with SCD are being screened by their healthcare providers at a much lower rate than the general pediatric population. More specifically, many children with SCD were being screened for NDD, but not ASD. Among screened children, a majority were screened with non-standardized (or poorly documented) tools or outside the age guidelines recommended by ASH and AAP (see Figure 2). Children among ND and ASD assessment groups exhibited similar percentages of NDD diagnosis, which may highlight disparities in screening and early detection of these disorders; NDDs may have also been diagnosed later in life these patients. Guidelines regarding developmental screening in pediatric SCD were released in mid-2020; given the short timeline, we did not expect to see changes in practice from this chart review. However, the AAP has guidelines for developmental surveillance and screening since 2004. Due to study design, limitations include lack of access to some data at the time of review, as patient medical records were switched to another electronic system. Additionally, standardized tools may have been used but not documented in patient charts.In conclusion, it is crucial to know the utility of these assessments in this vulnerable population. A future study could examine how the rates of screening and surveillance have changed since the guidelines release, using these data for comparison purposes. [Display omitted] DisclosuresCasella: Mast Pharmaceuticals (previously Adventrx Pharmaceuticals): Consultancy, Honoraria, Patents & Royalties. Lance: Novartis: Other: participated in research advisory board in 2020.

De novo variants in CACNA1E found in patients with intellectual disability, developmental regression and social cognition deficit but no seizures

BackgroundDe novo variants in the voltage-gated calcium channel subunit α1 E gene (CACNA1E) have been described as causative of epileptic encephalopathy with contractures, macrocephaly and dyskinesias.MethodsFollowing the observation of an index patient with developmental delay and autism spectrum disorder (ASD) without seizures who had a de novo deleterious CACNA1E variant, we screened GeneMatcher for other individuals with CACNA1E variants and neurodevelopmental phenotypes without epilepsy. The spectrum of pathogenic CACNA1E variants was compared to the mutational landscape of variants in the gnomAD control population database.ResultsWe identified seven unrelated individuals with intellectual disability, developmental regression and ASD-like behavioral profile, and notably without epilepsy, who had de novo heterozygous putatively pathogenic variants in CACNA1E. Age of onset of clinical manifestation, presence or absence of regression and degree of severity were variable, and no clear-cut genotype–phenotype association could be recognized. The analysis of disease-associated variants and their comparison to benign variants from the control population allowed for the identification of regions in the CACNA1E protein that seem to be intolerant to substitutions and thus more likely to harbor pathogenic variants. As in a few reported cases with CACNA1E variants and epilepsy, one patient showed a positive clinical behavioral response to topiramate, a specific calcium channel modulator.LimitationsThe significance of our study is limited by the absence of functional experiments of the effect of identified variants, the small sample size and the lack of systematic ASD assessment in all participants. Moreover, topiramate was given to one patient only and for a short period of time.ConclusionsOur results indicate that CACNA1E variants may result in neurodevelopmental disorders without epilepsy and expand the mutational and phenotypic spectrum of this gene. CACNA1E deserves to be included in gene panels for non-specific developmental disorders, including ASD, and not limited to patients with seizures, to improve diagnostic recognition and explore the possible efficacy of topiramate.