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Background: Executive functions (EF) have been identified as impaired in FXS, but few studies have examined their developmental trajectories., Aims: The primary aim of this longitudinal study was to examine the development of EF in young males with FXS compared to Mental Age (MA)-matched controls., Methods and Procedures: The sample comprised 56 boys with FXS (ages 7-13 years), and 48 MA-matched typical boys (ages 4-8 years). EF tasks included measures of inhibitory control, working memory, cognitive flexibility/set-shifting, problem solving/planning, and processing speed. Tasks were administered at three time points over five-years., Outcomes and Results: The MA-Matched Typical boys significantly outperformed the FXS boys on all EF tasks, with the FXS Group showing a pattern of slow, but positive growth on most EF tasks. For working memory tasks, significant interactions were noted between MA and autism symptom severity, and MA and medication status. The probability of task completion increased with higher MA., Conclusions and Implications: These findings contribute to our understanding of the development of EF in this population. They also lay the foundation for use of EF tasks in treatment efforts, particularly with respect to documenting improvements and practice effects, and in understanding associations with targeted developmental outcomes., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: The possibility of newborn screening for fragile X syndrome is complicated by the potential for identifying premutation carriers. Although knowing the child's carrier status has potential benefits, the possibility of late-onset disorders in carrier children and their parents raises concerns about whether such information would be distressing to parents and potentially more harmful than helpful. This study sought to answer this question by offering voluntary fragile X screening to new parents and returning results for both the full mutation and premutation FMR1 gene expansions. We tested the assumption that such information could lead to adverse mental health outcomes or decision regret. We also wanted to know if child age and spousal support were associated with the outcomes of interest., Methods: Eighteen mothers of screen-positive infants with the premutation and 15 comparison mothers completed a battery of assessments of maternal anxiety, postpartum depression, stress, family quality of life, decision regret, and spousal support. The study was longitudinal, with an average of 3 assessments per mother., Results: The premutation group was not statistically different from the comparison group on measures of anxiety, depression, stress, or quality of life. A subset of mothers experienced clinically significant anxiety and decision regret, but factors associated with these outcomes could not be identified. Greater spousal support was generally associated with more positive outcomes., Conclusions: Although we did not find evidence of significant adverse events, disclosure of newborn carrier status remains an important consideration in newborn screening policy., (Copyright © 2015 by the American Academy of Pediatrics.)

Background: Fragile X syndrome (FXS) and Down syndrome (DS) are the two leading genetic causes of intellectual disability, and FXS is the most common known genetic condition associated with autism. Both FXS and DS are associated with significant language impairment, but little is known about expressive language across domains over time or the role of autism in language development in FXS., Aims: To compare three domains of language production (vocabulary, syntax, pragmatics) over time within and across groups of boys with FXS with and without autism spectrum disorder (FXS-ASD, FXS-O), boys with DS, and typically developing (TD) boys., Methods & Procedures: Twenty-nine boys with FXS-O, 40 boys with FXS-ASD, 34 boys with DS, and 48 younger TD boys of similar non-verbal mental age living in the United States participated in the study. The Antonyms, Syntax Construction and Pragmatic Judgment subtests of the Comprehensive Assessment of Spoken Language were administered annually over 3 years., Outcomes & Results: TD boys scored higher than all other groups on all three subtests; boys with FXS-O and FXS-ASD scored higher than boys with DS in Syntax Construction; and boys with FXS-O scored higher than boys with FXS-ASD in Pragmatic Judgment. Within-group patterns varied between groups. Overall, the TD group showed significantly more change over time than all other groups., Conclusions & Implications: Findings suggest that expressive language skills and growth across various domains are more impaired in boys with FXS and DS than would be expected based on non-verbal mental age, that for boys with DS syntax is more impaired than would be expected based on intellectual disability, and that autism status affects pragmatic language in boys with FXS. Findings suggest that language production across domains should be addressed during assessment and intervention for boys with FXS and boys with DS, with differing group profiles also suggesting potentially different areas of focus., (© 2013 Royal College of Speech and Language Therapists.)

Substantial phenotypic overlap exists between fragile X syndrome (FXS) and autism, suggesting that FMR1 (the gene causing FXS) poses a significant risk for autism. Cross-population comparisons of FXS and autism therefore offer a potentially valuable method for refining the range of phenotypes associated with variation in FMR1. This study adopted a broader phenotype approach, focusing on parents who are at increased genetic liability for autism or FXS. Women who were carriers of FMR1 in its premutation state were compared with mothers of individuals with autism, and controls in an attempt to determine whether subtle features of the broad autism phenotype may express at elevated rates among FMR1 premutation carriers. The principal personality and language features comprising the broad autism phenotype (i.e., rigid and aloof personality, and particular patterns of pragmatic language use) were assessed among 49 premutation carriers who were mothers of individuals with FXS, 89 mothers of individuals with autism, and 23 mothers of typically developing individuals. Relative to controls, the autism and premutation parent groups showed elevated rates of certain personality and language characteristics of the broad autism phenotype. Findings suggest partially overlapping personality and language profiles among autism and premutation parent groups, with rigid personality style and patterns of pragmatic language use emerging as features most clearly shared between groups. These results provide further evidence for the overlap of autism and FXS, and may implicate FMR1 in some of the subtle features comprising the broad autism phenotype., (Copyright © 2012 Wiley Periodicals, Inc.)

Verbal perseveration is a frequently reported language characteristic of males with Fragile X syndrome and may be a defining feature or hallmark of the syndrome. We compared the verbal perseveration of boys with Fragile X syndrome with (n  =  29) and without (n  =  30) autism spectrum disorder, boys with Down syndrome (n  =  27), and typically developing boys (n  =  25) at similar nonverbal mental ages. During a social interaction, boys with both Fragile X syndrome and autism spectrum disorder produced significantly more topic perseveration than all other groups. In social interaction as compared to narration, boys with Fragile X syndrome (regardless of autism status) produced significantly more topic perseveration. These findings suggest that autism status, as well as language sampling context, affect perseveration in boys with Fragile X syndrome.

Objective: The goal of this study was to document rates of parental consent in a pilot study of newborn screening for FMR1 gene expansions, examine demographic characteristics of mothers who consented or declined, describe the reasons for their decision, and discuss ethical and social aspects of the consent process., Methods: A brief survey was used to record basic demographic data from mothers and an open-ended question was used to elicit parents' reasons for accepting or declining screening. A descriptive analysis was conducted on the number of mothers who consented to or declined screening, and a logistic regression model predicted mothers' likelihood to agree to screening based on demographic characteristics. Reasons for decisions were analyzed using content analysis. The study was conducted at University of North Carolina Hospitals. A total of 2137 mothers were approached., Results: The uptake rate for couples was 63%. Acceptance rates varied by race/ethnicity, with black respondents being less likely to accept screening. Primary reasons for accepting were "to know," "belief in research," and "the test was minimal/no risk." Reasons for declining included not wanting to know or worry, not being a good time, and issues with testing children or with genetic tests., Conclusions: Findings demonstrate that a majority of parents accepted newborn screening for FMR1 gene expansions, but decision rates and reasons for accepting or declining varied in part as a function of race/ethnicity and in part as a function of what parents most valued or feared in their assessment of risks and benefits.

Background: Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability, and the most common single gene disorder associated with autism. Language impairments in this disorder are well documented, but the nature and extent of syntactic impairments are still unclear., Aims: To compare the performance of boys with FXS with and without autism spectrum disorder on measures of verb (VM) and noun (NM) morphosyntax with that of typically developing boys of similar non-verbal mental ages., Methods & Procedures: Conversational samples were obtained from 33 boys with FXS with autism spectrum disorder (FXS-ASD), 35 boys with FXS and no ASD (FXS-O), and 46 typically developing boys (TD). Production of verbal and nominal morphosyntax was assessed separately in these two subdomains. A hierarchical linear model compared morphosyntactic scores in all groups after adjusting for non-verbal cognition, articulatory skill, and caregiver education. The model also tested interactions between group and morphosyntactic subdomain., Outcomes & Results: Boys with FXS in both groups scored lower than the TD boys on both measures. The FXS-O and the FXS-ASD groups did not differ on either composite measure. All covariates were significantly related to morphosyntactic scores., Conclusions & Implications: Part of the morphosyntactic impairment in FXS may be attributable to cognitive, environmental, and speech factors. However, it is clear that boys with FXS perform at levels lower than expected from differences in these extra-linguistic factors alone, across both the verb and the noun domains. Clinical interventions should therefore seek to address specific syntactic targets., (© 2010 Royal College of Speech & Language Therapists.)

Background: Variability in behaviour displayed by children with fragile X syndrome (FXS) may be partially attributable to environmental factors such as maternal responsivity. The purpose of this study was to explore variables associated with maternal behaviour during a task designed to elicit frustration in their children with FXS., Methods: Forty-six mother-child dyads, in which the child had full-mutation FXS, were observed in their homes during a task designed to elicit frustration in the child. Each child was given a wrong set of keys and asked to open a box to retrieve a desired toy. Mothers were provided with the correct set of keys and instructed to intervene when they perceived their child was getting too frustrated. Child-expressed frustration and requests for help and maternal behaviours (comforting, negative control, and encouraging/directing) were observed and coded. Maternal variables (e.g. depression, stress, education levels), child variables (e.g. autistic behaviours, age, medication use) and child behaviours (frustration, requests for help) were explored as predictors of maternal behaviour., Results: Almost all mothers intervened to help their children and most used encouraging/directing behaviours, whereas very few used comforting or negative control. Child age and child behaviours during the frustrating event were significant predictors of encouraging/directing behaviours in the mothers. Children whose mothers reported higher depressive symptomology used fewer requests for help, and mothers of children with more autistic behaviours used more negative control., Conclusions: The results of this study suggest that child age and immediate behaviours are more strongly related to maternal responsivity than maternal traits such as depression and stress.

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.

Purpose: To compare the phonological accuracy and speech intelligibility of boys with fragile X syndrome with autism spectrum disorder (FXS-ASD), fragile X syndrome only (FXS-O), Down syndrome (DS), and typically developing (TD) boys., Method: Participants were 32 boys with FXS-O (3-14 years), 31 with FXS-ASD (5-15 years), 34 with DS (4-16 years), and 45 TD boys of similar nonverbal mental age. We used connected speech samples to compute measures of phonological accuracy, phonological process occurrence, and intelligibility., Results: The boys with FXS, regardless of autism status, did not differ from TD boys on phonological accuracy and phonological process occurrence but produced fewer intelligible words than did TD boys. The boys with DS scored lower on measures of phonological accuracy and occurrence of phonological processes than all other groups and used fewer intelligible words than did TD boys. The boys with FXS and the boys with DS did not differ on measures of intelligibility., Conclusions: Boys with FXS, regardless of autism status, exhibited phonological characteristics similar to those of younger TD children but were less intelligible in connected speech. Boys with DS showed greater delays in all phonological measures than the boys with FXS and the TD boys.

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.

One hundred eight carrier mothers (95 premutation, 13 full mutation) of children with the full mutation fragile X syndrome completed seven scales to assess maternal stress, depressive symptoms, anger, anxiety, quality of life, hope, and optimism. A wide range of responses was found on each measure, with most mothers scoring in the non-clinical range on any individual measure. However, nearly half of the mothers scored in the clinically significant range on at least one measure and 25% on two or more measures. High stress and low quality of life were the most common domains of concern. Mothers with the full mutation generally did not differ from mothers with the premutation. CGG repeat length was not associated with responses on any of the measures completed by mothers with the premutation. Severity of the child's delay was not associated with any of the outcome measures, but child behavior problems accounted for significant variance in stress, depressive symptoms, anxiety, anger, and quality of life. Maternal adaptation appears to be a multidimensional phenomenon experienced in unique ways by each mother. Most mothers experienced positive adaptation, but a subset appear to be more vulnerable, especially those with children who have significant behavior problems. Future research needs to identify family, child, and support factors associated with maternal vulnerability and how adaptation changes over time in response to these factors., ((c) 2008 Wiley-Liss, Inc.)

Purpose: This study compared the syntax of boys who have fragile X syndrome (FXS) with and without autism spectrum disorder (ASD) with that of (a) boys who have Down syndrome (DS) and (b) typically developing (TD) boys., Method: Thirty-five boys with FXS only, 36 boys with FXS with ASD, 31 boys with DS, and 46 TD boys participated. Conversational language samples were evaluated for utterance length and syntactic complexity (i.e., Index of Productive Syntax; H. S. Scarborough, 1990)., Results: After controlling for nonverbal mental age and maternal education levels, the 2 FXS groups did not differ in utterance length or syntactic complexity. The FXS groups and the DS group produced shorter, less complex utterances overall and less complex noun phrases, verb phrases, and sentence structures than did the TD boys. The FXS with ASD group and the DS group, but not the FXS-only group, produced less complex questions/negations than did the TD group. Compared with the DS group, both FXS groups produced longer, more complex utterances overall, but on the specific complexity measures, they scored higher only on questions/negations., Conclusion: Boys with FXS and DS have distinctive language profiles. Although both groups demonstrated syntactic delays, boys with DS showed greater delays.

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.

The performance of 54 boys with fragile X syndrome (FXS), ages 7 to 13 years, was compared to that of a group of typically developing boys who were matched on mental age (MA) and ethnicity across multiple measures of executive function (EF). Boys with FXS varied in their ability to complete EF measures, with only 25.9% being able to complete a set-shifting task and 94.4% being able to complete a memory for word span task. When compared to the control group, and controlling for MA and maternal education, boys with FXS showed significant deficits in inhibition, working memory, cognitive flexibility/set-shifting, and planning. No group differences were observed in processing speed. Mental age significantly impacted performance on working memory, set-shifting, planning, and processing speed tasks for both groups. In boys with FXS, MA significantly predicted performance on working memory and set-shifting tasks. Our findings suggest that deficits in EF in boys with FXS are not solely attributable to developmental delays but, rather, present as a true array of neurocognitive deficits.

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., ((c) 2007 Wiley-Liss, Inc.)

Parent- and teacher-report of attention-deficit/hyperactivity disorder (ADHD) symptoms were examined using problem behavior and DSM-IV symptom inventory questionnaires for 63 children with full mutation fragile X syndrome (FXS) and 56 children without disabilities matched on mental age (MA). Prevalence rates of ADHD symptoms varied depending on type of measure (problem behavior or DSM-IV criteria), subscale (ADHD-inattentive or ADHD-hyperactive), scoring method (continuous T-scores or categorical scores based on DSM-IV algorithm), and rater (parent or teacher). Overall, 54-59% of boys with FXS met diagnostic behavioral criteria for either ADHD-inattentive type only, ADHD-hyperactive type only, or ADHD-combined type based on parent or teacher report. Boys with FXS were rated as having clinically high scores or met diagnostic criteria at higher rates than expected for the general population and had higher raw scores than their MA-matched peers. Parent ratings of boys with FXS resulted in higher ADHD-inattentive type and ADHD-hyperactive type T-scores than teachers. Boys who were rated as meeting DSM-IV criteria were more likely to be taking psychotropic medication and to have younger mental ages. Parents were substantially more likely than teachers to rate boys as meeting DSM-IV criteria for ADHD-inattentive type, while teachers were only slightly more likely than parents to rate boys as meeting DSM-IV criteria for ADHD-hyperactive type. Teachers were more likely than parents to rate boys as meeting DSM-IV criteria for ADHD when boys had lower levels 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.

This study compared the oral structure and oral-motor skills of 59 boys with fragile X syndrome (FXS), 34 boys with Down syndrome (DS), and 36 developmentally similar typically developing (TD) boys. An adaptation of the J. Robbins and T. Klee (1987) Oral Speech Motor Protocol was administered to participants and their scores on measures of oral structure and accuracy on speech motor and oral-motor tasks were analyzed. Boys with FXS scored lower than TD boys on oral structure, most oral function tasks, and all speech function tasks. Boys with DS scored lower than boys with FXS and TD boys on oral structure, and lower than TD boys on 1 oral function task and all speech function tasks. Boys with FXS and TD boys scored higher on speech function than oral function tasks, while boys with DS scored higher on oral function than speech function tasks. Boys with FXS and boys with DS repeated single syllable words with greater accuracy than multiple syllable words, while the TD boys produced both types of words with equal accuracy. These results suggest that boys with FXS and boys with DS exhibit atypical oral structure and motor function, yet differ in specific oral-motor patterns.

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.