Acoustic properties of early vocalizations in infants with fragile X syndrome.

Fragile X syndrome (FXS) is a neurogenetic syndrome characterized by cognitive impairments and high rates of autism spectrum disorder (ASD). FXS is often highlighted as a model for exploring pathways of symptom expression in ASD due to the high prevalence of ASD symptoms in this population and the known single-gene cause of FXS. Early vocalization features-including volubility, complexity, duration, and pitch-have shown promise in detecting ASD in idiopathic ASD populations but have yet to be extensively studied in a population with a known genetic cause for ASD such as FXS.

Infant Social Avoidance Predicts Autism but Not Anxiety in Fragile X Syndrome.

Autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and anxiety are three of the most common childhood psychiatric disorders. Early trajectories of social avoidance have been linked with these psychiatric disorders in previous studies, but it remains unclear how social avoidance differentially predicts comorbid disorders in a high-risk genetic subgroup. Here, we delineate the association between trajectories of social avoidance from infancy and subsequent ASD, ADHD, and anxiety outcomes at preschool in children with fragile X syndrome (FXS), a well-characterized single-gene disorder highly associated with social avoidance as well as elevated rates of ASD, ADHD, and anxiety.

Validating and Applying the CSBS-ITC in Neurogenetic Syndromes.

Although social communication skills are commonly delayed in children with neurogenetic syndromes (NGS), skill profiles in very young children are largely under characterized, in part due to the lack of validated assessment measures appropriate for these populations. We addressed this gap by validating and applying a popular early social communication screening measure, the Communication and Symbolic Behavior Scales Developmental Profile - Infant-Toddler Checklist (CSBS-ITC) in three previously understudied neurogenetic groups: Angelman, Prader-Willi, and Williams syndromes. Our results suggest that when used within the appropriate scope of screening and surveillance, the CSBS-ITC detects meaningful variability in skills across ages in young children with NGS and may provide useful information about both individual- and population-level social communication profiles in these populations.

Brief Report: Challenging Behaviors in Toddlers and Preschoolers with Angelman, Prader-Willi, and Williams Syndromes.

Children with neurogenetic syndromes (NGS) experience comorbid challenging behaviors and psychopathology. We examined challenging behaviors in 86 toddlers and preschoolers across three NGS [Angelman syndrome (AS), Prader-Willi syndrome (PWS), and Williams syndrome (WS)] and 43 low-risk controls (LRC), using the Child Behavior Checklist for Ages 1½-5. Challenging behavior profiles differed across NGS, with generally elevated behaviors in AS and WS, but not PWS, relative to LRC.

Infant Temperament in the 1 Premutation and Fragile X Syndrome.

Although temperament has been studied for decades as a predictor of psychopathology in the general population, examining temperament in neurogenetic groups has unique potential to inform the genetic and biological factors that may confer risk for psychopathology in later development. The present study examined early temperament in two heritable neurogenetic conditions associated with atypical CGG repeat expansions on the 1 gene: the 1 premutation (FXpm; 55-200 repeats) and fragile X syndrome (FXS; > 200 repeats). We focus specifically on the FXpm, as the condition is highly prevalent (1:209-291 female individuals, 1:430-855 male individuals) and has been preliminarily associated with increased risk for pediatric psychopathology, including attention problems, autism, and anxiety.

Curvilinear Association Between Language Disfluency and CGG Repeat Size Across the Normal, Intermediate, and Premutation Range.

Historically, investigations of have focused almost exclusively on the clinical effects of CGG expansion within the categories of the premutation (55-200 CGG repeats) and fragile X syndrome (>200 CGG repeats). However, emerging evidence suggests that CGG-dependent phenotypes may occur across allele sizes traditionally considered within the "normal" range. This study adopted an individual-differences approach to determine the association between language production ability and CGG repeat length across the full range of normal, intermediate, and premutation alleles.

Heart rate-defined sustained attention in infants at risk for autism.

Background: Although aberrant visual attention has been identified in infants at high familial risk for autism, the developmental emergence of atypical attention remains unclear. Integrating biological measures of attention into prospective high-risk infant studies may inform more nuanced developmental trajectories, clarifying the onset and course of atypical attention and potentially advancing early screening or treatment protocols. Heart rate-defined sustained attention (HRDSA) is a well-validated biological measure of attentional engagement that, in non-clinical infant populations, provides incremental information about attentional engagement beyond looking behaviors alone.

Sleep phenotypes in infants and toddlers with neurogenetic syndromes.

Background: Although sleep problems are well characterized in preschool- and school-age children with neurogenetic syndromes, little is known regarding the early emergence of these problems in infancy and toddlerhood. To inform syndrome-specific profiles and targets for intervention, we compared parent-reported sleep problems in infants and toddlers with Angelman syndrome (AS), Williams syndrome (WS), and Prader-Willi syndrome (PWS) with patterns observed among same-aged typically developing (TD) controls.

Methods: Mothers of 80 children (18 AS, 19 WS, 19 PWS, and 24 TD) completed the Brief Infant Sleep Questionnaire.

Neural correlates of face processing in etiologically-distinct 12-month-old infants at high-risk of autism spectrum disorder.

Neural correlates of face processing were examined in 12-month-olds at high-risk for autism spectrum disorder (ASD), including 21 siblings of children with ASD (ASIBs) and 15 infants with fragile X syndrome (FXS), as well as 21 low-risk (LR) controls. Event-related potentials were recorded to familiar and novel face and toy stimuli. All infants demonstrated greater N290 amplitude to faces than toys.

Prevalence of Autism Spectrum Disorders Among Children With Intellectual Disability.

Autism spectrum disorders (ASD) often co-occur with intellectual disability (ID) and are associated with poorer psychosocial and family-related outcomes than ID alone. The present study examined the prevalence, stability, and characteristics of ASD estimates in 2,208 children with ASD and ID identified through the South Carolina Autism and Developmental Disabilities Network. The prevalence of ASD in ID was 18.

Brief Report: Autism Symptoms in Infants with Fragile X Syndrome.

Fragile X syndrome (FXS) is the most common known genetic cause of autism spectrum disorder (ASD). Although 50-75 % of children with FXS meet ASD criteria, no studies have compared ASD symptoms in infants with FXS versus other high risk groups, such as siblings of children with ASD (ASIBs). Using the Autism Observation Scale for Infants, our findings indicate that 53 % of 12-month infants with FXS fall in the "at risk" category compared to 17 and 6 % for age-matched ASIBs and controls, respectively.

Trajectory and Predictors of Depression and Anxiety Disorders in Mothers With the FMR1 Premutation.

Background: Although the FMR1 premutation is associated with elevated prevalence of psychiatric disorders, the longitudinal course of symptoms has not been established. The present study followed a sample of women with the FMR1 premutation to characterize the incidence, stability, and predictors of mood and anxiety disorders across a 3-year period.

Methods: Participants included 83 women with the FMR1 premutation (mean age = 38.

Developmental trajectories of attentional control in preschool males with fragile X syndrome.

Attention problems are among the most impairing features associated with fragile X syndrome (FXS). However, few studies have examined behavioral development of inhibitory control in very young children with FXS. We examined attentional control in 3-6 year boys with FXS using both an experimental inhibitory control paradigm and parent-report of attention problems.

Maternal predictors of anxiety risk in young males with fragile X.

Children with fragile X syndrome (FXS) demonstrate high rates of anxiety disorders, with 65-83% meeting diagnostic criteria. The severity of anxiety symptoms in FXS has been shown to be partially predicted by elevated negative affect across early childhood [Tonnsen et al. (2013a); J Abnorm Child Psychol 41:267-280].

Biobehavioral indicators of social fear in young children with fragile X syndrome.

Anxiety is among the most impairing conditions associated with Fragile X syndrome (FXS) and is putatively linked to atypical physiological arousal. However, few studies have examined this association in young children with FXS. The authors examined whether patterns of arousal and behavior during an experimental stranger approach paradigm differ between a cross-sectional sample of 21 young children with FXS and 19 controls (12-58 months old).

Temperament factor structure in fragile X syndrome: the children's behavior questionnaire.

Early patterns of temperament lay the foundation for a variety of developmental constructs such as self-regulation, psychopathology, and resilience. Children with fragile X syndrome (FXS) display unique patterns of temperament compared to age-matched clinical and non-clinical samples, and early patterns of temperament have been associated with later anxiety in this population. Despite these unique patterns in FXS and recent reports of atypical factor structure of temperament questionnaires in Williams Syndrome (Leyfer, John, Woodruff-Borden, & Mervis, 2012), no studies have examined the latent factor structure of temperament scales in FXS to ensure measurement validity in this sample.

Early negative affect predicts anxiety, not autism, in preschool boys with fragile X syndrome.

Children with fragile X syndrome (FXS) face high risk for anxiety disorders, yet no studies have explored FXS as a high-risk sample for investigating early manifestations of anxiety outcomes. Negative affect is one of the most salient predictors of problem behaviors and has been associated with both anxiety and autistic outcomes in clinical and non-clinical pediatric samples. In light of the high comorbidity between autism and anxiety within FXS, the present study investigates the relationship between longitudinal trajectories of negative affect (between 8 and 71 months) and severity of anxiety and autistic outcomes in young males with FXS (n = 25).

Treatment effects of stimulant medication in young boys with fragile X syndrome.

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability and is caused by a CGG repeat expansion at Xq27.3 on the FMR1 gene. The majority of young boys with FXS display poor attention and hyperactivity that is disproportionate to their cognitive disability, and approximately 70% meet diagnostic criteria for attention-deficit/hyperactivity disorder.