Characterizing executive functioning and associated behaviors in individuals with dual-specificity tyrosine phosphorylation-regulated kinase 1A () syndrome.

Introduction: , a protein kinase located on human chromosome 21, plays a role in postembryonic neuronal development and degeneration. Alterations to have been consistently associated with cognitive functioning and neurodevelopmental disorders (e.g.

Visual and auditory attention in individuals with DYRK1A and SCN2A disruptive variants.

This preliminary study sought to assess biomarkers of attention using electroencephalography (EEG) and eye tracking in two ultra-rare monogenic populations associated with autism spectrum disorder (ASD). Relative to idiopathic ASD (n = 12) and neurotypical comparison (n = 49) groups, divergent attention profiles were observed for the monogenic groups, such that individuals with DYRK1A (n = 9) exhibited diminished auditory attention condition differences during an oddball EEG paradigm whereas individuals with SCN2A (n = 5) exhibited diminished visual attention condition differences noted by eye gaze tracking when viewing social interactions. Findings provide initial support for alignment of auditory and visual attention markers in idiopathic ASD and neurotypical development but not monogenic groups.

Predicting Intervention Use in Youth with Rare Variants in Autism-Associated Genes.

Specialized multidisciplinary supports are important for long-term outcomes for autistic youth. Although family and child factors predict service utilization in autism, little is known with respect to youth with rare, autism-associated genetic variants, who frequently have increased psychiatric, developmental, and behavioral needs. We investigate the impact of family factors on service utilization to determine whether caregiver (autistic features, education, income) and child (autistic features, sex, age, IQ, co-occurring conditions) factors predicted service type (e.

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

Background: Neurodevelopmental conditions such as intellectual disability (ID) and autism spectrum disorder (ASD) can stem from a broad array of inherited and de novo genetic differences, with marked physiological and behavioral impacts. We currently know little about the psychiatric phenotypes of rare genetic variants associated with ASD, despite heightened risk of psychiatric concerns in ASD more broadly. Understanding behavioral features of these variants can identify shared versus specific phenotypes across gene groups, facilitate mechanistic models, and provide prognostic insights to inform clinical practice.

Rhythmic attentional sampling in autism.

Individuals diagnosed with autism often display alterations in visual spatial attention toward visual stimuli, but the underlying cause of these differences remains unclear. Recent evidence has demonstrated that covert spatial attention, rather than remaining constant at a cued location, samples stimuli rhythmically at a frequency of 4-8 Hz (theta). Here we tested whether rhythmic sampling of attention is altered in autism.

Characterizing Sensory Phenotypes of Subgroups with a Known Genetic Etiology Pertaining to Diagnoses of Autism Spectrum Disorder and Intellectual Disability.

We aimed to identify unique constellations of sensory phenotypes for genetic etiologies associated with diagnoses of autism spectrum disorder (ASD) and intellectual disability (ID). Caregivers reported on sensory behaviors via the Sensory Profile for 290 participants (younger than 25 years of age) with ASD and/or ID diagnoses, of which ~ 70% have a known pathogenic genetic etiology. Caregivers endorsed poor registration (i.

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.

De novo variants in genes regulating stress granule assembly associate with neurodevelopmental disorders.

Stress granules (SGs) are cytoplasmic assemblies in response to a variety of stressors. We report a new neurodevelopmental disorder (NDD) with common features of language problems, intellectual disability, and behavioral issues caused by de novo likely gene-disruptive variants in , which encodes an essential regulator of SG assembly. haploinsufficiency in mouse led to social and cognitive impairments accompanied by disrupted neurogenesis and reduced SG formation during early brain development.

GIGYF1 disruption associates with autism and impaired IGF-1R signaling.

Autism spectrum disorder (ASD) represents a group of neurodevelopmental phenotypes with a strong genetic component. An excess of likely gene-disruptive (LGD) mutations in GIGYF1 was implicated in ASD. Here, we report that GIGYF1 is the second-most mutated gene among known ASD high-confidence risk genes.

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.

Family Empowerment: Predicting Service Utilization for Children with Autism Spectrum Disorder.

Families of children with autism spectrum disorder (ASD) often utilize a variety of services. Relatively few studies have examined the relationship between family empowerment and service utilization for this population. The present study investigated the relationship between family empowerment and service utilization in families of children with ASD from the Pacific Northwest.

The CHD8/CHD7/Kismet family links blood-brain barrier glia and serotonin to ASD-associated sleep defects.

Sleep disturbances in autism and neurodevelopmental disorders are common and adversely affect patient's quality of life, yet the underlying mechanisms are understudied. We found that individuals with mutations in , among the highest-confidence autism risk genes, or suffer from disturbed sleep maintenance. These defects are recapitulated in mutants affecting , the sole ortholog.

SPEN haploinsufficiency causes a neurodevelopmental disorder overlapping proximal 1p36 deletion syndrome with an episignature of X chromosomes in females.

Deletion 1p36 (del1p36) syndrome is the most common human disorder resulting from a terminal autosomal deletion. This condition is molecularly and clinically heterogeneous. Deletions involving two non-overlapping regions, known as the distal (telomeric) and proximal (centromeric) critical regions, are sufficient to cause the majority of the recurrent clinical features, although with different facial features and dysmorphisms.

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.

Developmental Predictors of Cognitive and Adaptive Outcomes in Genetic Subtypes of Autism Spectrum Disorder.

Approximately one-fourth of autism spectrum disorder (ASD) cases are associated with a disruptive genetic variant. Many of these ASD genotypes have been described previously, and are characterized by unique constellations of medical, psychiatric, developmental, and behavioral features. Development of precision medicine care for affected individuals has been challenging due to the phenotypic heterogeneity that exists even within each genetic subtype.

Transcriptional subtyping explains phenotypic variability in genetic subtypes of autism spectrum disorder.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by deficits in social communication and presence of restricted, repetitive behaviors, and interests. However, individuals with ASD vary significantly in their challenges and abilities in these and other developmental domains. Gene discovery in ASD has accelerated in the past decade, and genetic subtyping has yielded preliminary evidence of utility in parsing phenotypic heterogeneity through genomic subtypes.

Episignatures Stratifying Helsmoortel-Van Der Aa Syndrome Show Modest Correlation with Phenotype.

Helsmoortel-Van der Aa syndrome (HVDAS) is a neurodevelopmental condition associated with intellectual disability/developmental delay, autism spectrum disorder, and multiple medical comorbidities. HVDAS is caused by mutations in activity-dependent neuroprotective protein (ADNP). A recent study identified genome-wide DNA methylation changes in 22 individuals with HVDAS, adding to the group of neurodevelopmental disorders with an epigenetic signature.

Co-occurring medical conditions among individuals with ASD-associated disruptive mutations.

Children with autism spectrum disorder (ASD) are at risk for co-occurring medical conditions, many of which have also been reported among individuals with mutations in ASD-associated genes. This study examined rates of co-occurring medical conditions across 301 individuals with disruptive mutations to 1 of 18 ASD-risk genes in comparison to rates of conditions in an idiopathic ASD sample. Rates of gastrointestinal problems, seizures, physical anomalies, and immune problems were generally elevated, with significant differences in rates observed between groups.

Examining the Impact of Group Size on the Treatment Intensity of a Tier 2 Mathematics Intervention Within a Systematic Framework of Replication.

Group size and treatment intensity are understudied topics in mathematics intervention research. This study examined whether the treatment intensity and overall intervention effects of an empirically validated Tier 2 mathematics intervention varied between intervention groups with 2:1 and 5:1 student-teacher ratios. Student practice opportunities and the quality of explicit instruction served as treatment intensity metrics.

Comparing the effects of massed and distributed practice on skill acquisition for children with autism.

We replicated and extended the findings of Haq and Kodak (2015) by evaluating the efficiency of massed and distributed practice for teaching tacts and textual and intraverbal behavior to 3 children with autism. Massed practice included all practice opportunities conducted on 1 day during each week, and distributed practice included practice opportunities conducted across several days during the week. The results indicated that distributed practice was more efficient for all participants.