Discovering a new part of the phenotypic spectrum of Coffin-Siris syndrome in a fetal cohort.

PURPOSE: Genome-wide sequencing is increasingly being performed during pregnancy to identify the genetic cause of congenital anomalies. The interpretation of prenatally identified variants can be challenging and is hampered by our often limited knowledge of prenatal phenotypes. To better delineate the prenatal phenotype of Coffin-Siris syndrome (CSS), we collected clinical data from patients with a prenatal phenotype and a pathogenic variant in one of the CSS-associated genes. METHODS: Clinical data was collected through an extensive web-based survey. RESULTS: We included 44 patients with a variant in a CSS-associated gene and a prenatal phenotype; 9 of these patients have been reported before. Prenatal anomalies that were frequently observed in our cohort include hydrocephalus, agenesis of the corpus callosum, hypoplastic left heart syndrome, persistent left vena cava, diaphragmatic hernia, renal agenesis, and intrauterine growth restriction. Anal anomalies were frequently identified after birth in patients with ARID1A variants (6/14, 43%). Interestingly, pathogenic ARID1A variants were much more frequently identified in the current prenatal cohort (16/44, 36%) than in postnatal CSS cohorts (5%-9%). CONCLUSION: Our data shed new light on the prenatal phenotype of patients with pathogenic variants in CSS genes.

School-Implemented Interventions for Preschool to High School Students with Autism: An Update on Recent Research.

PURPOSE OF REVIEW: The purpose of this review is to provide an update on the recent research (2016-2021) that evaluates the effectiveness of school-implemented interventions for students with autism (3-21 years old) from preschool to high school. RECENT FINDINGS: Overall, the recent literature demonstrated that there are EBPs that help students with autism acquire a variety of skills across domains (academic, social communication). Though many educators and peers were able to achieve high-fidelity implementation, there remains variable fidelity of intervention use in some studies. Though there is some evidence that educators and peers can successfully implement interventions, there are additional focal areas that are missing from the literature that are needed in schools (e.g., mental health, vocational). Future research should leverage implementation science approaches to support the use of proven efficacious interventions in schools.

Gender and Autism Program: A novel clinical service model for gender-diverse/transgender autistic youth and young adults.

Objective: Situated in Children's National Hospital (CNH)'s Neuropsychology Division, the Gender and Autism Program (GAP) is the first clinical service dedicated to the needs of autistic gender-diverse/transgender youth. This study describes GAP clinical assessment profiles and presents a multi-perspective programmatic review of GAP evaluation services. Method: Seventy-five consecutive gender- and neuropsychologically-informed GAP evaluations were analyzed, including demographics, gender and autism characterization, and primary domains evaluated. Three program-based Delphi studies were conducted and identify: clinician priorities and challenges in providing care, program administrator lessons learned and ongoing barriers, and considerations adapting this model for a rural academic medical center. Results: Nearly two-thirds of referrals were transfeminine. Most youth had existing autism diagnoses; of those undiagnosed, three-quarters were found to be autistic. Five goals of evaluations were identified: Mental health was always assessed, and most evaluations also assessed gender-related needs in the context of autism neurodiversity. Neuropsychological characterization of strengths and challenges informed personalized accommodations to support youth gender-related self-advocacy. Clinicians emphasized frequent youth safety concerns. Administrators emphasized the need for specialized training for working with families. Components for adaptation of the GAP in a rural academic medical center were identified. Conclusions: Since its founding, the GAP has proven a sustainable neuropsychology-based service with consistent referral flow and insurance authorizations. Capturing staff perspectives through rigorous Delphi methods, and addressing the GAP's feasibility and replicability, this study provides a road map for replicating this service. We also highlight GAP training of specialist clinicians, fundamental to addressing the desperate shortage of providers in this field.

Concordance of multiple informant assessment of school-based social skills intervention and association with child outcomes: Results from a randomized trial.

Background: Fidelity, or the degree to which an intervention is implemented as designed, is essential for effective implementation. There has been a growing emphasis on assessing fidelity of evidence-based practices for autistic children in schools. Fidelity measurement should be multidimensional and focus on core intervention components and assess their link with program outcomes. This study evaluated the relation between intervention fidelity ratings from multiple sources, tested the relation between fidelity ratings and child outcomes, and determined the relations between core intervention components and child outcomes in a study of an evidence-based psychosocial intervention designed to promote inclusion of autistic children at school, Remaking Recess. Method: This study extends from a larger randomized controlled trial examining the effect of implementation support on Remaking Recess fidelity and child outcomes. Schools were randomized to receive the intervention or the intervention plus implementation support. Observers, intervention coaches, and school personnel completed fidelity measures to rate completion and quality of intervention delivery. A measure of peer engagement served as the child outcome. Pearson correlation coefficients were calculated to determine concordance between raters. Two sets of hierarchical linear models were conducted using fidelity indices as predictors of peer engagement. Results: Coach- and self-rated completion and quality scores, observer- and self-rated quality scores, and observer- and coach-rated quality fidelity scores were significantly correlated. Higher observer-rated completion and quality fidelity scores were predictors of higher peer engagement scores. No single intervention component emerged as a significant predictor of peer engagement. Conclusions: This study demonstrates the importance of using a multidimensional approach for measuring fidelity, testing the link between fidelity and child outcomes, and examining how core intervention components may be associated with child outcomes. Future research should clarify how to improve multi-informant reports to provide "good enough" ratings of fidelity that provide meaningful information about outcomes in community settings. Plain Language Summary: Fidelity is defined as how closely an intervention is administered in the way the creators intended. Fidelity is important because it allows researchers to determine what exactly is leading to changes. In recent years, there has been an interest in examining fidelity of interventions for autistic children who receive services in school. This study looked at the relationship between fidelity ratings from multiple individuals, the relationship between fidelity and child outcomes, and the relationship between individual intervention component and child changes in a study of Remaking Recess, an intervention for autistic children at school. Schools were randomly selected to receive the intervention only or the intervention plus implementation support from the research team. Observers, intervention coaches, and individuals delivering the intervention themselves completed fidelity measures. Child engagement with peers was measured before and after the intervention. Several measures of self-, coach-, and observer-report fidelity were associated with each other. Higher observer-reported fidelity was associated with higher child peer engagement scores. No single intervention step was linked to child peer engagement and both treatment groups had similar outcomes in terms of fidelity. This study shows the importance of having multiple raters assess different parts of intervention fidelity, looking at the link between fidelity and child outcomes, and seeing how individual intervention steps may be related to outcomes. Future research should aim to find out which types of fidelity ratings are "good enough" to lead to positive changes following treatment so that those aspects can be used and targeted in the future.

"On an island by myself": implications for the inclusion of autistic students in self-contained classrooms in public elementary schools.

Introduction: Autistic students have limited access to inclusive classes and activities in their schools. Principals and special education teachers who directly teach and administer programs for autistic elementary students can offer critical insight into factors, such as educators' attitudes, that may impact inclusive opportunities in schools. These attitudes may serve as barriers to or facilitators of promoting an inclusive school setting. Methods: Semi-structured interviews with 26 elementary school principals and 26 special education teachers explored their experiences implementing evidence-based practices for autistic students (pivotal response training, discrete trial training, and visual schedules) in 26 self-contained classrooms in the United States. Autism-specific culture and inclusion emerged as a theme, which was analyzed for this paper. Results: An inductive approach to thematic analysis revealed principals' and special education teachers' perspectives regarding the "autism-specific culture" in the school, including attitudes towards and inclusion of autistic students in self-contained classrooms in the broader school environment. Analysis of text related to "autism-specific culture" detailed aspects of inclusion, factors (i.e., barriers and facilitators) affecting inclusion, principals' and special education teachers' attitudes towards autistic students placed in self-contained classrooms, attitudes of other school staff towards teachers in self-contained classrooms, and recommendations to support an inclusive school environment for autistic students. Discussion: Results suggest that valuing "equal" access to classes and activities for autistic students in self-contained classrooms may not be sufficient for promoting an inclusive school environment, Educators may benefit from targeted strategies to facilitate inclusion. Strategies range from supporting educators' attitudes and knowledge of autism to shifting physical aspects of the school environment (e.g., location of classrooms). Additional implications for supporting the true inclusion (i.e., inclusion that goes beyond physical inclusion) involves of autistic students in self-contained classrooms schools are discussed.

Genetic Ablation of GIGYF1, Associated With Autism, Causes Behavioral and Neurodevelopmental Defects in Zebrafish and Mice.

BACKGROUND: Autism spectrum disorder is characterized by deficits in social communication and restricted or repetitive behaviors. Due to the extremely high genetic and phenotypic heterogeneity, it is critical to pinpoint the genetic factors for understanding the pathology of these disorders. METHODS: We analyzed the exomes generated by the SPARK (Simons Powering Autism Research) project and performed a meta-analysis with previous data. We then generated 1 zebrafish knockout model and 3 mouse knockout models to examine the function of GIGYF1 in neurodevelopment and behavior. Finally, we performed whole tissue and single-nucleus transcriptome analysis to explore the molecular and cellular function of GIGYF1. RESULTS: GIGYF1 variants are significantly associated with various neurodevelopmental disorder phenotypes, including autism, global developmental delay, intellectual disability, and sleep disturbance. Loss of GIGYF1 causes similar behavioral effects in zebrafish and mice, including elevated levels of anxiety and reduced social engagement, which is reminiscent of the behavioral deficits in human patients carrying GIGYF1 variants. Moreover, excitatory neuron-specific Gigyf1 knockout mice recapitulate the increased repetitive behaviors and impaired social memory, suggesting a crucial role of Gigyf1 in excitatory neurons, which correlates with the observations in single-nucleus RNA sequencing. We also identified a series of downstream target genes of GIGYF1 that affect many aspects of the nervous system, especially synaptic transmission. CONCLUSIONS: De novo variants of GIGYF1 are associated with neurodevelopmental disorders, including autism spectrum disorder. GIGYF1 is involved in neurodevelopment and animal behavior, potentially through regulating hippocampal CA2 neuronal numbers and disturbing synaptic transmission.

Age-Based Tracks: A Method to Tailor Autism Diagnostic Evaluation in Large-Scale Autism Specialty Centers.

This paper describes a proposed model of diagnostic evaluation for autism spectrum disorder (ASD) at a large-scale ASD specialty center. Our center has implemented age-based diagnostic tracks within an interdisciplinary team evaluation approach to assessing ASD. Data were collected as part of a program evaluation and included responses from provider surveys as well as patient medical record reviews. The results from 803 patients were included. The diagnostic outcomes, time for evaluation, and appropriateness of referral were analyzed in patients referred to the Younger (n = 155) and Older (n = 648) diagnostic tracks. In 92.8% of cases referred to the clinic's standard team evaluation model, the provider teams were able to make a diagnostic decision within the allotted evaluation time. The results from an additional diagnostic pathway, termed the Autism Psych Team (APT), within the older track were also presented. The intake providers had the option to triage older patients to this pathway when they anticipated that the patient might be diagnostically complex. Most patients (45.1%) triaged to the APT were referred due to psychiatric complexity. In 96% of APT cases, the APT providers felt the patient was an appropriate referral. Overall, these results suggest a method to efficiently triage patients to diagnostic models equipped to serve them within a high-volume ASD center.

Brief Report: Associations Between Self-injurious Behaviors and Abdominal Pain Among Individuals with ASD-Associated Disruptive Mutations.

Self-injurious behaviors (SIB) are elevated in autism spectrum disorder (ASD) and related genetic disorders, but the genetic and biological mechanisms that contribute to SIB in ASD are poorly understood. This study examined rates and predictors of SIB in 112 individuals with disruptive mutations to ASD-risk genes. Current SIB were reported in 30% of participants and associated with poorer cognitive and adaptive skills. History of severe abdominal pain predicted higher rates of SIB and SIB severity after controlling for age and adaptive behavior; individuals with a history of severe abdominal pain were eight times more likely to exhibit SIB than those with no history. Future research is needed to examine associations between genetic risk, pain, and SIB in this population.

A Pilot Project Using Pediatricians as Initial Diagnosticians in Multidisciplinary Autism Evaluations for Young Children.

OBJECTIVES: Wait times for autism spectrum disorder (ASD) evaluations are long, thereby delaying access to ASD-specific services. We asked how our traditional care model (requiring all patients to see psychologists for ASD diagnostic decisions) compared to an alternative model that better utilizes the available clinicians, including initial evaluation by speech, audiology, and pediatrics (trained in Level 2 autism screening tools). Pediatricians could diagnose immediately if certain about diagnosis but could refer uncertain cases to psychology. Accuracy and time to diagnosis, charges, and parent satisfaction were our main outcome measures. METHODS: Data were gathered through record extraction (n = 244) and parent questionnaire (n = 57). We compared time to diagnosis, charges, and parent satisfaction between traditional and alternative models. Agreement between pediatrician and psychologist diagnoses was examined for a subset (n = 18). RESULTS: The alternative model's time to diagnosis was 44% faster (85 vs 152 d) and 33% less costly overall. Diagnostic agreement was 93% for children with ASD diagnoses and 100% for children without ASD diagnoses. Pediatricians expressed higher diagnostic certainty about children with higher levels of ASD symptoms. Parents reported no differences in high satisfaction with experiences, family-centered care, and shared decision making. CONCLUSION: Efficient use of available clinicians with additional training in Level 2 autism screening resulted in improvements in time to diagnosis and reduced charges for families. Coordination of multidisciplinary teams makes this possible, with strategic sequencing of patients through workflow. Flexibility was key to not only allowing pediatricians to refer uncertain cases to psychology for diagnosis but also allowing for diagnosis by a pediatrician when symptomatic presentation clearly met diagnostic criteria.