Commentary: Best practices and processes for assessment of autism spectrum disorder - the intended role of standardized diagnostic instruments.

Development of standardized diagnostic instruments has facilitated the systematic characterization of individuals with autism spectrum disorders (ASD) in clinical and research settings. However, overemphasis on scores from specific instruments has significantly detracted from the original purpose of these tools. Rather than provide a definitive "answer," or even a confirmation of diagnosis, standardized diagnostic instruments were designed to aid clinicians in the process of gathering information about social communication, play, and repetitive and sensory behaviors relevant to diagnosis and treatment planning. Importantly, many autism diagnostic instruments are not validated for certain patient populations, including those with severe vision, hearing, motor, and/or cognitive impairments, and they cannot be administered via a translator. In addition, certain circumstances, such as the need to wear personal protective equipment (PPE), or behavioral factors (e.g., selective mutism) may interfere with standardized administration or scoring procedures, rendering scores invalid. Thus, understanding the uses and limitations of specific tools within specific clinical or research populations, as well as similarities or differences between these populations and the instrument validation samples, is paramount. Accordingly, payers and other systems must not mandate the use of specific tools in cases when their use would be inappropriate. To ensure equitable access to appropriate assessment and treatment services, it is imperative that diagnosticians be trained in best practice methods for the assessment of autism, including if, how, and when to appropriately employ standardized diagnostic instruments.

ASD symptoms in adults with ADHD: a comparative study using ADOS-2.

In this study, we examined autism spectrum disorder (ASD) symptoms in adults with attention-deficit hyperactivity disorder (ADHD) in comparison with normal controls using the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2). Sixty-three adults with ADHD (mean age, 35.3 years; 38 men) and 31 controls (mean age, 38.7 years; 17 men) completed Module 4 of the ADOS-2, Autism Spectrum Quotient, Conners' Adult ADHD Rating Scale, and Wechsler Adult Intelligence Scale, Third Edition. Adults with ADHD were not clinically diagnosed with ASD, and their ADHD diagnosis was based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. Between-group comparisons on the scoring patterns revealed significant ASD symptoms present in adults with ADHD, which was congruent with our previous study. Further, item level and correlation analyses showed the possibility that ASD symptoms in adult ADHD comprised of two distinct mechanisms, one qualitatively similar to ASD and the other arising from ADHD characteristics, highlighting the complex nature of ADHD-ASD symptom overlaps.

ASD symptoms in adults with ADHD: a preliminary study using the ADOS-2.

Attention-deficit/hyperactivity disorder (ADHD) has long been regarded as disparate and mutually exclusive to autism spectrum disorder (ASD) in the Diagnostic and Statistical Manual of Mental Disorders (DSM)-III-R and DSM-IV. However, this idea has become obsolete due to a growing body of evidence suggesting numerous phenotypic and genetic similarities between ADHD and ASD. ASD symptoms or autistic traits in individuals with ADHD have been examined; however, most studies were conducted on children and relied on self- or parent- reports. ASD symptoms assessed with more direct, objective measures, such as the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) in adults with ADHD, remain understudied. In the present study, we used the ADOS-2 to evaluate ASD symptoms in adults with ADHD who were not clinically diagnosed with ASD. Fifty-six adults (mean age 33.9 years, 35 males, intelligence quotient ≥ 85), who were diagnosed with ADHD based on the DSM-5 criteria, completed Module 4 of the ADOS-2. Autism Spectrum Quotient (AQ), Conners' Adult ADHD Rating Scale (CAARS), and Wechsler Adult Intelligence Scale (WAIS)-III were also administered to assess self-rated ASD symptoms, ADHD symptoms, and intelligence, respectively. Overall, 23.3% of participants met the ASD diagnostic classification on the ADOS-2. Social reciprocal interaction scores tended to be higher, while restricted and repetitive behavior scores were low. The scoring patterns and possible overlapping and differing phenotypic characteristics of ADHD and ASD are discussed.

Predicting diagnostic outcome in adult autism spectrum disorder using the autism diagnostic observation schedule, second edition.

BACKGROUND: The Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) module four assessment for diagnosing autism spectrum disorder in adults has shown good sensitivity and specificity in research settings. METHOD: This study aimed to evaluate the predictive accuracy of the ADOS-2 module four by investigating the components of the assessment, in relation to diagnostic outcome in a clinical setting. Data from 88 service users referred to a Specialist Adult Autism Service was explored. RESULTS: ADOS-2 scores failed to predict the diagnostic outcome (overall sensitivity = 92%, specificity = 57%). Interestingly, scores from the 'restricted interests' component of the ADOS-2 have the potential to predict diagnostic outcome, despite this domain not been included in the scoring algorithm. CONCLUSIONS: Based on our findings, we recommend clinicians are cautious when interpreting results of the ADOS-2 assessment.

Stability of the Initial Diagnosis of Autism Spectrum Disorder by DSM-5 in Children: A Short-Term Follow-Up Study.

BACKGROUND: Assessing the stability of the diagnosis of autism spectrum disorder (ASD) in children is important. Only few such studies have been reported from India. We aimed to assess the stability after 18-30 months, of an initial diagnosis of ASD based on DSM-5, in children ≤ 5 years of age using Autism Diagnostic Observation Schedule, 2nd Edition (ADOS-2). METHODS: A total of 125 children with ASD diagnosed by DSM-5 at ≤ 5 years of age were followed up at 18-30 months using ADOS-2, which is considered as the 'gold-standard' observational assessment for diagnosing ASD and hence suitable for confirming the stability of the diagnosis. RESULTS: Similar to previous studies from developed countries, the stability of ASD diagnosis was 80%. There was no significant correlation between gender, socioeconomic status and the stability of the final diagnosis. All the children continued to have some developmental difficulties mainly in the domain of language, attention or social communication. CONCLUSION: Our results suggest that DSM-5 can be used for the initial diagnosis ASD to initiate early intervention for children with this condition in resource-limited set-ups. Adequately powered prospective studies with long-term follow-up are needed to confirm our findings.

Utility of the ADOS-2 in children with psychiatric disorders.

The Autism Diagnostic Observation Schedule (ADOS-2) is commonly used in the diagnosis of autism spectrum disorder (ASD). Although it has demonstrated good sensitivity and specificity in research settings, relatively little is known about its utility and accuracy in children and adolescents with co-occurring psychiatric disorders. We investigated this topic in children with acute psychiatric disorders. Our sample consisted of 58 patients, aged 9-18 years, admitted to a child and adolescent psychiatric inpatient unit with a suspected diagnosis of ASD. Both Modules 3 and 4 demonstrated low sensitivity (Module 3: 58.3%; Module 4: 55.6%) and specificity (Module 3: 56.5%; Module 4: 59.5%). These findings suggest that the ADOS-2 should be interpreted with caution while screening for autism in children with complex psychiatric disorders.

Clinician Opinions Regarding the Usefulness of the BOSA for ASD Assessment in a Service for Children Aged Under 12 Years.

The COVID-19 pandemic and the subsequent social distancing policies forced healthcare teams to drastically alter the way they deliver services. This was particularly challenging for clinicians involved in diagnosing autism spectrum disorder (ASD), as assessment tools and methods required face-to-face social interactions between clinicians and children. To address this, the Brief Observation of Symptoms of Autism (BOSA) was developed to ensure that people suspected of ASD can receive diagnostic assessments during the pandemic. This project aimed to explore clinicians' opinions on the BOSA, particularly regarding the usefulness of the assessment for clinicians to clarify diagnostic outcomes of ASD assessments. Both quantitative and qualitative data was gathered within an NHS community paediatric team. This included a questionnaire for clinicians to complete, and data from the BOSA assessments done in the service. Thematic analysis and descriptive statistics revealed that many clinicians felt that the BOSA can be beneficial in certain cases, such as selective mutism, and found the BOSA particularly helpful for observing parent-child interactions. These findings highlighted important information that the Autism Diagnostic Observation Schedule Second Edition (ADOS-2) does not give opportunities to observe. Clinicians reported that at times, the BOSA materials, brevity and parental administration created barriers to gathering information for diagnostic decisions. As may be expected, clinicians showed a clear preference for the more familiar and validated ADOS-2. However, the study highlights perceived limitations of the ADOS-2 and strengths of the BOSA, with recommendations made for future practice and research.

A Validation Study of the CARS-2 Compared With the ADOS-2 in the Diagnosis of Autism Spectrum Disorder: A Suggestion for Cutoff Scores.

Objectives: This study examined the validity of the Childhood Autism Rating Scale, Second Edition (CARS-2) compared with the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) in identifying autism spectrum disorder (ASD). Methods: A total of 237 children were tested using both the CARS-2 and ADOS-2. We examined the correlation using Pearson's correlation analysis. In addition, we used a receiver operating characteristic graph to determine the optimal standard version of the CARS-2 (CARS2-ST) cutoff score for ASD diagnosis using the ADOS-2. Results: The concurrent validity of the CARS2-ST was demonstrated by a significant correlation with the ADOS-2 (r=0.864, p<0.001). The optimal CARS2-ST cutoff scores were 30 and 28.5 for identifying autism and autism spectrum, respectively, based on the ADOS-2. Conclusion: We suggest a newly derived CARS2-ST cutoff score of 28.5 for screening ASD and providing early intervention.

Diagnostic assessment of autism in adults - current considerations in neurodevelopmentally informed professional learning with reference to ADOS-2.

Services for the assessment and diagnosis of autism in adults have been widely criticized and there is an identified need for further research in this field. There is a call for diagnostic services to become more accessible, person-centered, neurodiversity affirming, and respectful. There is a need for workforce development which will increase capacity for diagnostic assessment and support for adults. ADOS-2 is a gold-standard diagnostic assessment tool for autism recommended in clinical guidelines. However, diagnostic procedures such as the ADOS-2 are rooted in the medical model and do not always sit comfortably alongside the neurodiversity paradigm or preferences of the autistic community. Training and educational materials need to account for the differences between these approaches and support clinicians to provide services which meet the needs of the adults they serve. The National Autism Implementation Team worked alongside ADOS-2 training providers to support clinicians in Scotland, to provide effective and respectful diagnostic assessment. The team engaged with clinicians who had attended ADOS training to identify areas of uncertainty or concern. Training materials were developed to support ADOS assessors to incorporate key principles including "nothing about us without us"; "difference not deficit"; "environment first"; "diagnosis matters," "language and mindsets matter"; and "a neurodevelopmental lens," to support the provision of neurodiversity affirming assessment practice. The National Autism Implementation Team also provided examples of actions which can be undertaken by clinicians to improve the assessment experience for those seeking a diagnosis. Training materials are based on research evidence, clinical experience, and the needs and wishes of autistic people.

A Machine Learning Approach to the Diagnosis of Autism Spectrum Disorder and Multi-Systemic Developmental Disorder Based on Retrospective Data and ADOS-2 Score.

Early and accurate diagnosis of autism spectrum disorders (ASD) and tailored therapeutic interventions can improve prognosis. ADOS-2 is a standardized test for ASD diagnosis. However, owing to ASD heterogeneity, the presence of false positives remains a challenge for clinicians. In this study, retrospective data from patients with ASD and multi-systemic developmental disorder (MSDD), a term used to describe children under the age of 3 with impaired communication but with strong emotional attachments, were tested by machine learning (ML) models to assess the best predictors of disease development as well as the items that best describe these two autism spectrum disorder presentations. Maternal and infant data as well as ADOS-2 score were included in different ML testing models. Depending on the outcome to be estimated, a best-performing model was selected. RIDGE regression model showed that the best predictors for ADOS social affect score were gut disturbances, EEG retrievals, and sleep problems. Linear Regression Model showed that term pregnancy, psychomotor development status, and gut disturbances were predicting at best for the ADOS Repetitive and Restricted Behavior score. The LASSO regression model showed that EEG retrievals, sleep disturbances, age at diagnosis, term pregnancy, weight at birth, gut disturbances, and neurological findings were the best predictors for the overall ADOS score. The CART classification and regression model showed that age at diagnosis and weight at birth best discriminate between ASD and MSDD.

Construction of copy number variation landscape and characterization of associated genes in a Bangladeshi cohort of neurodevelopmental disorders.

Introduction: Copy number variations (CNVs) play a critical role in the pathogenesis of neurodevelopmental disorders (NDD) among children. In this study, we aim to identify clinically relevant CNVs, genes and their phenotypic characteristics in an ethnically underrepresented homogenous population of Bangladesh. Methods: We have conducted chromosomal microarray analysis (CMA) for 212 NDD patients with male to female ratio of 2.2:1.0 to identify rare CNVs. To identify candidate genes within the rare CNVs, gene constraint metrics [i.e., "Critical-Exon Genes (CEGs)"] were applied to the population data. Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) was followed in a subset of 95 NDD patients to assess the severity of autism and all statistical tests were performed using the R package. Results: Of all the samples assayed, 12.26% (26/212) and 57.08% (121/212) patients carried pathogenic and variant of uncertain significance (VOUS) CNVs, respectively. While 2.83% (6/212) patients' pathogenic CNVs were found to be located in the subtelomeric regions. Further burden test identified females are significant carriers of pathogenic CNVs compared to males (OR = 4.2; p = 0.0007). We have observed an increased number of Loss of heterozygosity (LOH) within cases with 23.85% (26/109) consanguineous parents. Our analyses on imprinting genes show, 36 LOH variants disrupting 69 unique imprinted genes and classified these variants as VOUS. ADOS-2 subset shows severe social communication deficit (p = 0.014) and overall ASD symptoms severity (p = 0.026) among the patients carrying duplication CNV compared to the CNV negative group. Candidate gene analysis identified 153 unique CEGs in pathogenic CNVs and 31 in VOUS. Of the unique genes, 18 genes were found to be in smaller (<1 MB) focal CNVs in our NDD cohort and we identified PSMC3 gene as a strong candidate gene for Autism Spectrum Disorder (ASD). Moreover, we hypothesized that KMT2B gene duplication might be associated with intellectual disability. Conclusion: Our results show the utility of CMA for precise genetic diagnosis and its integration into the diagnosis, therapy and management of NDD patients.

Diagnostic validity of Autism Diagnostic Observation Schedule, second edition (K-ADOS-2) in the Korean population.

BACKGROUND: Although the Korean version of the Autism Diagnostic Observation Schedule-2 (K-ADOS-2) is widely being used to diagnose autism spectrum disorder (ASD) in South Korea, no previous study has examined the validity and reliability of all modules of K-ADOS-2 across a wide age range, particularly older children, adolescents, and adults. METHOD: Data from 2,158 participants were included (mean age = 79.7 months; 73.6% male): 1473 participants with ASD and 685 participants without ASD (Toddler Module, n = 289; Module 1, n = 642; Module 2 n = 574; Module 3 n = 411; Module 4, n = 242). Participants completed a battery of tests, including the K-ADOS or K-ADOS-2 and other existing diagnostic instruments. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve, positive predictive value (PPV), negative predictive value (NPV), Cohen's kappa (k), and agreement with existing diagnostic instruments were computed. Cronbach's α values were also calculated. RESULTS: All developmental cells of the K-ADOS-2 showed sufficient ranges of sensitivity 85.4-100.0%; specificity, 80.4-96.8%; area under the ROC curve, .90-.97; PPV, 77.8-99.3%; NPV, 80.6-100.0%; and k values, .83-.92. The kappa agreements of developmental cells with existing diagnostic instruments ranged from .20 to .90. Cronbach's α values ranged from .82 to .91 across all developmental cells. LIMITATION: The best-estimate clinical diagnoses made in this study were not independent of the K-ADOS-2 scores. Some modules did not include balanced numbers of participants in terms of gender and diagnostic status. CONCLUSION: The K-ADOS-2 is a valid and reliable instrument in diagnosing ASD in South Korea. Future studies exploring the effectiveness of the K-ADOS-2 in capturing restricted, repetitive behaviors and differentiating ASD from other developmental disabilities are needed.

Item-Based Analysis of Some ADOS-2 Items with Typically Developing Participants Might help Improve Cross-Cultural Validity of ADOS-2.

Most internationally recognized instruments for the screening and diagnosis of autism spectrum disorder have been developed in the USA, which calls into question the degree of their cultural adaptation to diverse populations. The aim of this study is to examine the characteristics of social communication in typically developing Croatian-speaking participants (N = 220) using ADOS-2-defined item-level normative values. Croatian subjects showed the expected ("typical") results in the domain of verbal communication, slightly atpical results in nonverbal communication (primarily gesture use), and more significant deviations in pragmatics (offering and asking for information), relative to the expectations of the ADOS-2. As ADOS-2 has become an important component of thorough ASD diagnostic evaluations worldwide, identifying methods for increasing the cross-cultural validity is essential.

Brief Report: Emotional and Behavioral Problems Among Young Children with ASD: An Exploratory Study of ADOS E-Codes and Child Characteristics.

Emotional and behavioral problems (EBPs), such as anxiety, overactivity, and aggression, can influence the diagnosis of autism spectrum disorder (ASD). The gold standard diagnostic tool for ASD, the Autism Diagnostic Observation Schedule-Second Edition, includes three items ("E-codes") for EBPs that are frequently associated with ASD. Few empirical investigations have explored the use of E-codes. This study examined the relationship between E-codes and child characteristics (e.g., cognitive abilities, ASD symptom severity) in a sample of young children with ASD (N = 233). Findings indicated that E-codes positively correlated with ASD symptom severity and negatively associated with IQ. Symptom severity also significantly accounted for the variance in EBPs. Implications for ASD assessment as well as future research are discussed.

Sex differences in social communication behaviors in toddlers with suspected autism spectrum disorder as assessed by the ADOS-2 toddler module.

LAY ABSTRACT: When toddlers are suspected of autism spectrum disorder (ASD), the gold-standard assessment technique is with the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) Toddler Module, a behavioral observation system. ASD is a neurodevelopmental condition more frequently diagnosed in toddler boys than in toddler girls. There is some evidence that the ADOS-2 assesses behaviors that are more characteristic of boys with ASD than girls. Thus, it is possible that focusing on these behaviors contributes at least in part to why more boys are diagnosed than girls. Specifically, girls may show more social skills than boys during the ADOS-2 assessment due to their socialization histories, which may lead to missed diagnoses of ASD in toddler girls. The current study examined eight social behaviors assessed by the ADOS-2 in a sample of toddlers with suspected ASD to see if they contributed differently to the total score of those items. Examination of those items suggested that those social communication behaviors work the same for boys and girls with suspected ASD, which was inconsistent with hypotheses. However, examination of particular items raises the possibility of examining creative/imaginative play as an area for future research.

Correlation Between Sialidase NEU1 mRNA Expression Changes in Autism Spectrum Disorder.

Abnormal alterations in enzymes functioned in sialic acid modifications may be associated with ASD. In order to study the differences in peripheral blood sialidase (neuraminidase 1; NEU1) mRNA expression between autism spectrum disorder (ASD) children and healthy control, and to examine the correlation between NEU1 mRNA expression and the main behavioral phenotypes in children with ASD, we performed RT-qPCR to measure NEU1 mRNA expression in peripheral blood of 42 children with ASD and 42 healthy controls. In addition, we used the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) to measure and evaluate the behavioral phenotypes of children with ASD. Our results showed that NEU1 mRNA in the ASD group was significantly higher than in the control group (P < 0.0001). In addition, the ADOS-2 diagnostic scores of 42 children with ASD were correlated with their NEU1 mRNA expression results (R = 0.344, P = 0.0257). Moreover, in general, NEU1 mRNA expression was also positively correlated with the Social Affect (SA) of ADOS-2 (R = 0.3598, P = 0.0193) but not with the Restricted and Repetitive Behavior (RRB) (R = 0.15, P = 0.3432). Our results indicated that sialidase NEU1 mRNA was significantly increased in children with ASD, and its expression was correlated with the SA of children with ASD, which suggested that sialidase NEU1 may affect the SA of ASD. Our data highlighted the potential of NEU1 expression change may play an important role in ASD disease and lay the foundation for further studies on the relationship between NEU1 and ASD.

Assessment of Autism Spectrum Disorder in Deaf Adults with Intellectual Disability: Feasibility and Psychometric Properties of an Adapted Version of the Autism Diagnostic Observation Schedule (ADOS-2).

This study describes the adaptation of the autism diagnostic observation schedule (ADOS-2) to assess autism spectrum disorder (ASD) in adults with intellectual disability (ID) and hearing loss who communicate primarily visually. This adapted ADOS-2 was applied to residents of specialized therapeutic living communities (n = 56). The internal consistency of the adapted ADOS-2 was excellent for the Social Affect of modules 2 and 3 and acceptable for Restricted and Repetitive Behaviors subscale of module 2, but poor for module 3. Interrater reliability was comparable to standard ADOS-2 modules 1-3. Results suggest that autism symptoms of deaf adults with ID can be reliably identified by an adapted ADOS-2, provided adequate expertise in deafness, ID, ASD and proficiency in signed language by the administrator.

Agreement between parents' and clinical researchers' ratings of behavioral problems in children with fragile X syndrome and chromosome 15 imprinting disorders.

BACKGROUND: Despite the increasing number of clinical trials involving children with neurodevelopmental disorders, appropriate and objective outcome measures for behavioral symptoms are still required. AIM: This study assessed the agreement between parents' and clinical researchers' ratings of behavioral problem severity in children with fragile X syndrome (FXS) and chromosome 15 imprinting disorders. METHODS AND PROCEDURES: The cohort comprised 123 children (64% males), aged 3-17 years, with FXS (n = 79), Prader-Willi (PWS; n = 19), Angelman (AS; n = 15), and Chromosome 15q duplication (n = 10) syndromes. Specific items from the Autism Diagnostic Observation Schedule-Second Edition and Aberrant Behavior Checklist-Community Edition mapping to corresponding behavioral domains were selected ad-hoc, to assess behavioral problems. OUTCOMES AND RESULTS: Inter-rater agreement for the cohort was slight for self-injury (Intraclass Correlation Coefficient (ICC) = 0.12), fair for tantrums/aggression (0.24) and mannerisms/stereotypies (0.25), and moderate for hyperactivity (0.48). When stratified by diagnosis, ICC ranged from poor (0; self-injury, AS and PWS) to substantial (0.48; hyperactivity, females with FXS). CONCLUSIONS AND IMPLICATIONS: The high level of inter-rater disagreement across most domains suggests that parents' and researchers' assessments led to discrepant appraisal of behavioral problem severity. These findings have implications for treatment targets and outcome measure selection in clinical trials, supporting a multi-informant approach.

Autism spectrum disorder symptom expression in individuals with 3q29 deletion syndrome.

BACKGROUND: The 1.6 Mb 3q29 deletion is associated with neurodevelopmental and neuropsychiatric phenotypes, including a 19-fold increased risk for autism spectrum disorder (ASD). Previous work by our team identified elevated social disability in this population via parent-report questionnaires. However, clinical features of ASD in this population have not been explored in detail. METHODS: Thirty-one individuals with 3q29 deletion syndrome (3q29del, 61.3% male) were evaluated using two gold-standard clinical ASD evaluations: the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2), and the Autism Diagnostic Interview, Revised (ADI-R). Four matched comparators for each subject were ascertained from the National Database for Autism Research. Item-level scores on the ADOS-2 and ADI-R were compared between subjects with 3q29del and matched comparators. RESULTS: Subjects with 3q29del and no ASD (3q29del-ASD) had greater evidence of social disability compared to typically developing (TD) comparison subjects across the ADOS-2. Subjects with 3q29del and ASD (3q29del + ASD) were largely indistinguishable from non-syndromic ASD (nsASD) subjects on the ADOS-2. 3q29del + ASD performed significantly better on social communication on the ADI-R than nsASD (3q29 + ASD mean = 11.36; nsASD mean = 15.70; p = 0.01), and this was driven by reduced deficits in nonverbal communication (3q29 + ASD mean = 1.73; nsASD mean = 3.63; p = 0.03). 3q29del + ASD reported significantly later age at the first two-word phrase compared to nsASD (3q29del + ASD mean = 43.89 months; nsASD mean = 37.86 months; p = 0.01). However, speech delay was not related to improved nonverbal communication in 3q29del + ASD. LIMITATIONS: There were not enough TD comparators with ADI-R data in NDAR to include in the present analysis. Additionally, our relatively small sample size made it difficult to assess race and ethnicity effects. CONCLUSIONS: 3q29del is associated with significant social disability, irrespective of ASD diagnosis. 3q29del + ASD have similar levels of social disability to nsASD, while 3q29del-ASD have significantly increased social disability compared to TD individuals. However, social communication is reasonably well preserved in 3q29del + ASD relative to nsASD. It is critical that verbal ability and social disability be examined separately in this population to ensure equal access to ASD and social skills evaluations and services.

Delineating the autistic phenotype in children with neurofibromatosis type 1.

BACKGROUND: Existing research has demonstrated elevated autistic behaviours in children with neurofibromatosis type 1 (NF1), but the autistic phenotype and its relationship to other neurodevelopmental manifestations of NF1 remains unclear. To address this gap, we performed detailed characterisation of autistic behaviours in children with NF1 and investigated their association with other common NF1 child characteristics. METHODS: Participants were drawn from a larger cross-sectional study examining autism in children with NF1. The population analysed in this study scored above threshold on the Social Responsiveness Scale-Second Edition (T-score ≥ 60; 51% larger cohort) and completed the Autism Diagnostic Interview-Revised (ADI-R) and/or the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2). All participants underwent evaluation of their intellectual function, and behavioural data were collected via parent questionnaires. RESULTS: The study cohort comprised 68 children (3-15 years). Sixty-three per cent met the ADOS-2 'autism spectrum' cut-off, and 34% exceeded the more stringent threshold for 'autistic disorder' on the ADI-R. Social communication symptoms were common and wide-ranging, while restricted and repetitive behaviours (RRBs) were most commonly characterised by 'insistence on sameness' (IS) behaviours such as circumscribed interests and difficulties with minor changes. Autistic behaviours were weakly correlated with hyperactive/impulsive attention deficit hyperactivity disorder (ADHD) symptoms but not with inattentive ADHD or other behavioural characteristics. Language and verbal IQ were weakly related to social communication behaviours but not to RRBs. LIMITATIONS: Lack of genetic validation of NF1, no clinical diagnosis of autism, and a retrospective assessment of autistic behaviours in early childhood. CONCLUSIONS: Findings provide strong support for elevated autistic behaviours in children with NF1. While these behaviours were relatively independent of other NF1 comorbidities, the importance of taking broader child characteristics into consideration when interpreting data from autism-specific measures in this population is highlighted. Social communication deficits appear similar to those observed in idiopathic autism and are coupled with a unique RRB profile comprising prominent IS behaviours. This autistic phenotype and its relationship to common NF1 comorbidities such as anxiety and executive dysfunction will be important to examine in future research. Current findings have important implications for the early identification of autism in NF1 and clinical management.