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Testing cognitive skill development is important for diagnostic, prognostic, and monitoring purposes, especially for young children and individuals with neurodevelopmental disorders. Developmental tests have been created for infants and toddlers, while traditional IQ tests are often employed beginning in the later preschool period. However, IQ tests rely on developmental skills that are rapidly changing during early childhood. Here, we introduce the idea of prerequisite skills in developmental domains, which are discrete skills required for, but not explicitly tested by, traditional IQ tests. Focusing on general cognition, particularly among children with a chronological or mental age under 4 years, may fail to capture important nuances in skill development. New skill-based assessments are needed in general, and in particular for categorization, which is foundational to higher-order cognitive skills. Novel measures quantifying categorization skills would provide a more sensitive measure of development for young children and older individuals with low developmental levels.

We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n=35,584 total samples, 11,986 with ASD). Using an enhanced Bayesian framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate ≤ 0.1. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained for severe neurodevelopmental delay, while 53 show higher frequencies in individuals ascertained for ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most of the risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In human cortex single-cell gene expression data, expression of risk genes is enriched in both excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory/inhibitory imbalance underlying ASD.

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Analysis of de novo CNVs (dnCNVs) from the full Simons Simplex Collection (SSC) (N = 2,591 families) replicates prior findings of strong association with autism spectrum disorders (ASDs) and confirms six risk loci (1q21.1, 3q29, 7q11.23, 16p11.2, 15q11.2-13, and 22q11.2). The addition of published CNV data from the Autism Genome Project (AGP) and exome sequencing data from the SSC and the Autism Sequencing Consortium (ASC) shows that genes within small de novo deletions, but not within large dnCNVs, significantly overlap the high-effect risk genes identified by sequencing. Alternatively, large dnCNVs are found likely to contain multiple modest-effect risk genes. Overall, we find strong evidence that de novo mutations are associated with ASD apart from the risk for intellectual disability. Extending the transmission and de novo association test (TADA) to include small de novo deletions reveals 71 ASD risk loci, including 6 CNV regions (noted above) and 65 risk genes (FDR ≤ 0.1). Through analysis of de novo mutations in autism spectrum disorder (ASD), Sanders et al. find that small deletions, but not large deletions/duplications, contain one critical gene. Combining CNV and sequencing data, they identify 6 loci and 65 genes associated with ASD.

Objectives Approximately 4% of children who are deaf or hard of hearing have co-occurring autism spectrum disorder (ASD). Making an additional diagnosis of ASD in this population can be challenging, given the complexities of determining whether speech/language and social delays can be accounted for by their hearing loss, or whether these delays might be indicative of a comorbid ASD diagnosis. This exploratory study described a population of 24 children with the dual diagnosis of ASD and hearing loss. Methods Children completed a comprehensive ASD evaluation using standardized autism diagnostic instruments (Autism Diagnostic Observation Schedule, language and psychological testing). Children with permanent hearing loss who had a developmental evaluation between 2001 and 2011 and were diagnosed with an ASD based on the results of that evaluation were included. Information on communication modality, language and cognitive abilities was collected. Results The median age of diagnosis was 14 months (range 1–71) for hearing loss and 66.5 months (range 33–106) for ASD. Only 25% (n = 6) children were diagnosed with ASD ≤48 months of age and 46% by ≤6 years. Twelve (50%) children were diagnosed with ASD, 11 were diagnosed with pervasive developmental disorder not otherwise specified and 1 child had Asperger's. Most (67%) had profound degree of hearing loss. Fourteen (58%) children had received a cochlear implant, while 3 children had no amplification for hearing loss. Nine (38%) of the 24 children used speech as their mode of communication (oral communicators). Conclusions Communication delays in children who are deaf or hard of hearing are a serious matter and should not be assumed to be a direct consequence of the hearing loss. Children who received cochlear implants completed a multidisciplinary evaluation including a developmental pediatrician, which may have provided closer monitoring of speech and language progression and subsequently an earlier ASD diagnosis. Because children who are deaf or hard of hearing with ASD are challenging to evaluate, they may receive a diagnosis of ASD at older ages.

OBJECTIVE: Growing awareness that symptoms of autism spectrum disorder (ASD) transcend multiple diagnostic categories, and major advances in the identification of genetic syndromes associated with ASD, have led to widespread use of ASD symptom measures in etiologic studies of neurodevelopmental disorders. Insufficient consideration of potentially confounding factors such as cognitive ability or behavior problems can have important negative consequences in interpretation of findings, including erroneous estimation of associations between ASD and etiologic factors.METHOD: Participants were 388 children 2 to 13 years old with diagnoses of ASD or another neurodevelopmental disorder without ASD. Receiver operating characteristics methods were used to assess the influence of IQ and emotional and behavioral problems on the discriminative ability of 3 widely used ASD symptom measures: the Social Responsiveness Scale (SRS), the Autism Diagnostic Interview-Revised (ADI-R), and the Autism Diagnostic Observation Schedule (ADOS).RESULTS: IQ influenced the discriminative thresholds of the SRS and ADI-R, and emotional and behavioral problems affected the discriminative thresholds of the SRS, ADI-R, and ADOS. This resulted in low specificity of ASD cutoffs on the SRS and ADI-R for children with intellectual disability without ASD (27-42%) and low specificity across all 3 instruments for children without ASD with increased emotional and behavioral problems (36-59%). Adjustment for these characteristics resulted in improved discriminative ability for all of the ASD measures.CONCLUSION: The findings indicate that scores on ASD symptom measures reflect far more than ASD symptoms. Valid interpretation of scores on these measures requires steps to account for the influences of IQ and emotional and behavioral problems.