The Emergence of Effortful Control in Young Boys With Fragile X Syndrome.

Effortful control, or the ability to suppress a dominant response to perform a subdominant response, is an early-emerging temperament trait that is linked with positive social-emotional development. Fragile X syndrome (FXS) is a single-gene disorder characterized by hallmark regulatory impairments, suggesting diminished effortful control. This study compared the development of effortful control in preschool boys with FXS ( n = 97) and typical development ( n = 32). Unlike their typical peers, the boys with FXS did not exhibit growth in effortful control over time, which could not be accounted for by adaptive impairments, FMR1 molecular measures, or autism symptoms. These results contribute to our understanding of the childhood phenotype of FXS that may be linked to the poor social-emotional outcomes seen in this group.

Language development in infants and toddlers with fragile X syndrome: change over time and the role of attention.

Fragile X syndrome (FXS) is associated with significant language and communication delays, as well as problems with attention. This study investigated early language abilities in infants and toddlers with FXS (n  =  13) and considered visual attention as a predictor of those skills. We found that language abilities increased over the study period of 9 to 24 months, with moderate correlations among language assessments. In comparison to typically developing infants (n  =  11), language skills were delayed beyond chronological age and developmental-level expectations. Aspects of early visual attention predicted later language ability. Atypical visual attention is an important aspect of the FXS phenotype with implications for early language development, particularly in the domain of vocabulary.

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. Study 1 examined attentional control in FXS compared to comparison groups matched on chronological and mental age. To determine the stability of impairments over time in FXS, Study 2 examined patterns of developmental change in an expanded longitudinal sample. Across studies, males with FXS demonstrated persistent impairments in inhibitory control and parent-reported attention problems. Inhibitory control was related to, but not solely driven by, lower mental age. Although parent-rated attention problems remained stable across ages, inhibitory control improved with time. Children with more severe attention problems often displayed initially poorer inhibitory control. However, these trajectories also improved more rapidly with age. Our findings indicate that despite persistent deficits in attentional control in young children with FXS, multi-method assessment can be used to capture developmental growth that should be further supported through early, targeted intervention.

Reading and phonological skills in boys with fragile X syndrome.

Although reading skills are critical for the success of individuals with intellectual disabilities, literacy has received little attention in fragile X syndrome (FXS). This study examined the literacy profile of FXS. Boys with FXS (n = 51; mean age 10.2 years) and mental age-matched boys with typical development (n = 35) participated in standardized assessments of reading and phonological skills. Phonological skills were impaired in FXS, while reading was on-par with that of controls. Phonological awareness predicted reading ability and ASD severity predicted poorer phonological abilities in FXS. Boys with FXS are capable of attaining reading skills that are commensurate with developmental level and phonological awareness skills may play a critical role in reading achievement in FXS.

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. The present study used confirmatory factor analysis to examine the factor structure of a well-validated parent-reported temperament questionnaire, the Children's Behavior Questionnaire (Rothbart, Ahadi, Hershey, & Fisher, 2001), in a sample of 90 males with FXS ages 3-9 years. Our data produced a similar, but not identical, three-factor model that retained the original CBQ factors of negative affectivity, effortful control, and extraversion/surgency. In particular, our FXS sample demonstrated stronger factor loadings for fear and shyness than previously reported loadings in non-clinical samples, consistent with reports of poor social approach and elevated anxiety in this population. Although the original factor structure of the Children's Behavior Questionnaire is largely retained in children with FXS, differences in factor loading magnitudes may reflect phenotypic characteristics of the syndrome. These findings may inform future developmental and translational research efforts.

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). Multilevel models indicated associations between elevated anxiety and higher fear and sadness, lower soothability, and steeper longitudinal increases in approach. Autistic outcomes were unrelated to negative affect. These findings suggest early negative affect differentially predicts anxiety, not autistic symptoms, within FXS. Future research is warranted to determine the specificity of the relationship between negative affect and anxiety, as well as to explore potential moderators. Characterizing the relationship between early negative affect and anxiety within FXS may inform etiology and treatment considerations specific to children with FXS, as well as lend insight into precursors of anxiety disorders in other clinical groups and community samples.

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). Groups did not differ in mean levels of behavioral fear. Unlike the control group, however, the FXS group demonstrated increased facial fear at older ages, as well as age-dependent changes in associations between heart activity and distress vocalizations. These findings may inform theoretical models of anxiety etiology in FXS and early detection efforts.

Visual attention and autistic behavior in infants with fragile X syndrome.

Aberrant attention is a core feature of fragile X syndrome (FXS), however, little is known regarding the developmental trajectory and underlying physiological processes of attention deficits in FXS. Atypical visual attention is an early emerging and robust indictor of autism in idiopathic (non-FXS) autism. Using a biobehavioral approach with gaze direction and heart activity, we examined visual attention in infants with FXS at 9, 12, and 18 months of age with a cross-sectional comparison to 12-month-old typically developing infants. Analyses revealed lower HR variability, shallower HR decelerations, and prolonged look durations in 12-month old infants with FXS compared to typical controls. Look duration and increased latency to disengage attention were correlated with severity of autistic behavior but not mental age.

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. Psychopharmacology is employed with 82% of young males 5-17 years of age, with stimulant medication as the most common medication prescribed. This study evaluated the effects of stimulant medication on the academic performance, attention, motor activity, and psychophysiological arousal of boys with FXS, as well as the concordance of effects within individuals. Participants in this study included 12 boys with FXS who were treated with stimulants. Participants completed videotaped academic testing on two consecutive days and were randomly assigned to be off stimulants for 1 day and on stimulants the other day. On each day, multiple measures including academic performance, behavior regulation, and psychophysiological arousal were collected. Approximately 75% of participants performed better on attention and academic measures, and 70% showed improved physiological regulation while on stimulant medication. A high degree of concordance among measures was found. Lower intelligence quotient (IQ), but not age, correlated with greater improvements in in-seat behavior. IQ and age did not relate to on-task behaviors. The frequency and magnitude of response to stimulant medication in boys with FXS is higher than those reported for most children with non-specific intellectual disabilities and autism spectrum disorder.

Developmental trajectories of young girls with fragile x syndrome.

To describe the early phenotype of girls with full mutation fragile X, we used 54 observations of 15 girls between the ages of 6 months and 9 years to examine developmental trajectories as measured by the Battelle Development Inventory. In this sample, autistic behavior was associated with poorer developmental outcomes, primarily due to interactions of age with autistic behavior, even though autistic behavior, measured continuously, was relatively mild. Although this small sample, ascertained primarily through male relatives with fragile X syndrome, limits generalizability, considerable variability in developmental outcome in young girls was documented. In addition, findings support previous research suggesting that even mild autistic behaviors in girls can be associated with developmental outcomes.

Trajectories and predictors of the development of very young boys with fragile X syndrome.

OBJECTIVE: To describe the development of young boys with fragile X syndrome (FXS). METHODS: Fifty-five boys (aged 8-48 months at study entry) with the full mutation FXS received multiple developmental assessments. RESULTS: As expected, the boys' rate of development was significantly lower than chronological age expectations. No evidence of slowing in the rate of development was found. Autistic behavior was negatively associated with development, but maternal IQ was not. Developmental delays were evident in some domains as early as 9 months; however, initial detection of delays is complicated by measures and criteria used. Developmental age scores at 31 months of age were related to scores obtained at 61 months of age only in the global composite and visual reception domain. CONCLUSIONS: Developmental delays are evident in some infants with FXS as young as 9 months of age. Pediatric psychologists need to be informed about the developmental profiles in young children with FXS to accurately diagnose, treat, and support these children and their families.

Developmental trajectories and correlates of sensory processing in young boys with fragile X syndrome.

BACKGROUND AND PURPOSE: No longitudinal study on sensory processing in children with fragile X syndrome (FXS) exists. This study examined developmental trajectories and correlates of sensory processing from infancy through preschool years in 13 boys with FXS. METHOD: Participants were assessed using observational and parent-report measures 2-6 times between 9 and 54 months of age. RESULTS: Over time, an increasing proportion of boys displayed sensory processing that differed significantly from test norms. Observational measures were more sensitive than parent-reports early in infancy. Age and developmental quotient significantly predicted levels of hyporesponsiveness; there was a trend for hyperresponsiveness to increase with age. Baseline physiological and biological measures were not predictive. CONCLUSIONS: Sensory processing problems are observable early and grow increasingly problematic from infancy through the preschool ages. Early identification and intervention may attenuate long-term difficulties for children with FXS.

Memory skills of boys with fragile X syndrome.

Multiple aspects of memory were examined in 42 boys with fragile X syndrome and a comparison group of 42 typically developing boys matched on MA. Working memory, incidental memory, and deliberate memory were assessed with a battery that included both free-recall and recognition tasks. Findings indicated that boys with fragile X syndrome performed more poorly than their matches on most measures. The exception was free recall, in which their accuracy was equal to that of the control participants. Results from analyses of a subset of boys with fragile X syndrome who exhibit characteristics of autism and their MA matches, though preliminary, support the conclusion that memory deficits are especially marked in boys who have fragile X syndrome and evidence autistic behaviors.

Babies Count: the national registry for children with visual impairments, birth to 3 years.

INTRODUCTION: Information about the prevalence of visual impairment in children is not collected systematically. Further, little information is available about children under age 6. Babies Count is a national registry of children with visual impairment in the United States, aged birth to 3 years. METHODS: Data were collected on 2,155 children at the point of entry into specialized early intervention programs. Data include patient diagnosis, functional vision, age, gender, ethnicity, and family characteristics. Concurrent visual pathology and systemic disabilities were also documented. RESULTS: Of the sample of 2,155 children, 1,167 (54%) were boys; approximately 40% of the children were legally blind, and 68% had disabilities in addition to visual impairment. Cortical visual impairment, retinopathy of prematurity (ROP), and optic nerve hypoplasia (ONH) were the three most prevalent visual conditions. In children with these three conditions, those with ROP were diagnosed the earliest (mean, 3.4 months), and those with cortical visual impairment were diagnosed latest (mean, 7.6 months). There was on average a 4.5 month mean lag between the diagnosis of children's visual impairment and referral for services. ONH carried a poorer visual outcome when compared with other diagnoses, including CVI, ROP, and albinism. CONCLUSIONS: Prevalent visual conditions in children in the United States differ from those found in developing countries and in adults with visual impairment. Babies Count is a comprehensive set of data that may affect our understanding of the epidemiology of visual impairment in the United States. In an era of preventive and outcome-based medicine, and with competition for health care and research funding, these data provide a valuable means for understanding the impact of these disorders on society.

Sustained attention and response inhibition in boys with fragile X syndrome: measures of continuous performance.

Sustained attention and response inhibition were examined in boys with full mutation fragile X syndrome (FXS) using adapted visual and auditory continuous performance tests (CPTs). Only 61% of 56 boys with visual CPT data and 54% of 52 boys with auditory data were able to demonstrate sufficient understanding to complete the visual and auditory CPTs, respectively. Mental age (MA) predicted whether boys with FXS were able to demonstrate understanding of the CPTs. The performance of boys with FXS who were able to complete the CPTs was compared to a sample of boys without disabilities matched on MA. Boys with FXS demonstrated similar or smaller declines in sustained attention over task time than their MA-matched peers on the visual and auditory CPTs, respectively, but consistently demonstrated greater declines in response inhibition over task time than their MA-matched peers. There were no differences between groups for response time of hits. Higher MAs consistently predicted better sustained attention and response inhibition over task time on the visual and auditory CPTs. Furthermore, boys taking psychotropic medication performed better at the beginning of most tasks, although their performance deteriorated at a faster rate over time, and boys rated as meeting diagnostic criteria for ADHD-hyperactive type had more difficulty over task time with response inhibition on the auditory CPT. For both boys with FXS and their MA matches, performance was better on the visual CPT than on the auditory CPT though this effect may be attributable to a number of factors other than the modality.

Social approach and autistic behavior in children with fragile X syndrome.

Social avoidance is a core phenotypic characteristic of fragile X syndrome (FXS) that has critical cognitive and social consequences. However, no study has examined modulation of multiple social avoidant behaviors in children with FXS. In the current study, we introduce the Social Approach Scale (SAS), an observation scale that includes physical movement, facial expression, and eye contact approach behaviors collected across multiple time points. Our findings suggested that social approach behaviors in children with FXS were affected by age, gender, setting, and time spent with an examiner. Selected social approach behaviors were related to autistic behavior. Increased eye contact over the course of a research assessment, in particular, was found to be a strong predictor of lower autistic behavior.

Temperament and vagal tone in boys with fragile X syndrome.

Physiological hyperarousal, an elevated state of physiological arousal and poor modulation, has been postulated to be a significant source of behavior problems in children with fragile X syndrome (FXS). Temperament has been associated with behavior problems and may also reflect biological reactivity. Young boys with FXS display poorly modulated and low levels of vagal tone (Roberts, Dev Psychobiol 2001;39:107-123) and high activity, poor attention, low adaptability, poor persistence, and low intensity when compared with a reference sample of typically developing (Hatton, Dev Med Child Neurol 1991;41:625-632). In this study, we integrated physiological indices of vagal tone with temperament ratings and compared a sample of 29 young boys with FXS to 31 typically developing boys matched on chronological age and ethnicity. Boys with FXS were more active, less adaptable, and less persistent than the comparison group. Boys with FXS also showed lower baseline levels and less suppression of vagal tone in response to changing task demands. A relationship between baseline vagal tone and persistence was shown across both groups. However, group differences in temperament dimensions did not appear to be mediated or moderated by vagal tone.

Autistic behavior in children with fragile X syndrome: prevalence, stability, and the impact of FMRP.

We examined autistic behavior in a cross-sectional sample of 179 children with fragile X syndrome (FXS) and a longitudinal subset of 116 children using the Childhood Autism Rating Scale (CARS) to (a) determine a prevalence of autistic behavior in FXS, (b) examine the stability of autistic ratings over time, and (c) assess the association between the fragile X mental retardation protein (FMRP) and autistic behavior. Approximately 21% of the sample of 129 children (25.9% of boys) scored at or above the cutoff for autism. CARS scores increased slowly, yet significantly, over time, and low levels of FMRP were associated with higher mean levels of autistic behavior as measured by the CARS.

Video analysis of sensory-motor features in infants with fragile X syndrome at 9-12 months of age.

This study utilized retrospective video analysis to distinguish sensory-motor patterns in infants with fragile X syndrome (FXS) (n = 11) from other infants [i.e., autism (n = 11), other developmental delay (n = 10), typical (n = 11)] at 9-12 months of age. Measures of development, autistic features, and FMRP were assessed at the time of entry into the study. Home videos collected from families were edited and coded with previously validated procedures. Findings revealed a pattern of sensory-motor features (e.g., repetitive leg movements, posturing, less sophistication/repetitive use of objects) associated with FXS, and suggest these infants were most similar to the group of infants with other developmental delays, irrespective of co-existing autistic symptoms later in life. Infant sensory-motor features in the FXS group were more predictive of an early developmental milestone (i.e., age walking) than later, more broad, developmental outcomes, or FMRP. Implications for early identification and differential diagnosis are discussed.

Academic skills of boys with fragile X syndrome: profiles and predictors.

The academic achievement of boys with fragile X syndrome and the relation between several predictive factors and academic performance are reported. Boys with fragile X syndrome displayed significant deficits in all academic skill areas. Relative strengths were observed in general knowledge, reflecting the ability to integrate experiential information. In contrast, relative weaknesses were observed in prewriting skills and visuospatial-processing abilities. The rate of academic growth slowed over time, and the decrease in rate was more pronounced in measures of core academic skills (e.g., prereading and math skills) than in broad-based tasks. Nonverbal IQ and FMR protein expression were not associated with the level or rate of change; however, autistic behavior and maternal education were related to academic achievement scores.