Deborah D. Hatton

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.

Evidence-Based Practices in Interventions for Children and Youth with Autism Spectrum Disorders

ABSTRACT Evidence-based practices (EBPs) are the basis on which teachers and other service providers are required to design educational programs for learners with autism spectrum disorders (ASD). As part of their work with the National Professional Development Center (NPDC) on ASD, researchers developed a process for reviewing the research literature and established criteria for identifying EBPs. In their review, they identified 24 focused intervention practices having sufficient evidence. In this article, the authors describe procedures for selecting specific EBPs appropriate for addressing specific IEP goals for learners with ASD. The authors emphasize the importance of systematic implementation of practices.

Autistic behavior in young boys with fragile X syndrome

A sample of 57 boys with fragile X syndrome (fraX) between the ages of 24 and 133 months was rated using the Childhood Autism Rating Scale (CARS) to assess the extent to which autism and autistic features were evident in a young population. Fourteen subjects (approximately 25% of the sample) scored above the cutoff for autism, suggesting a relatively high incidence of autistic behavior. All but 2 of these 14 were in the mildly or moderately autistic range, however, and only a few items received severe ratings, suggesting that severe autism is relatively rare in fraX, at least during the early years. The CARS resulted in a continuum of autistic ratings in the fraX population, but no particular items on the CARS contributed disproportionately to autism ratings. A visual comparison of ratings on an autistic, non-fraX sample revealed similar profiles of ratings, suggesting that differentiating fraX and autism on the basis of CARS ratings is not likely. Within the fraX group, chronological age and socioeconomic status did not correlate with CARS ratings, but severity of delay was strongly related, such that more severely delayed children scored higher (more autistic) on the CARS.

Autistic Behavior, FMR1 Protein, and Developmental Trajectories in Young Males with Fragile X Syndrome

In the context of a longitudinal study, we assessed the relationship between ratings of autistic behavior, FMR1 protein expression (FMRP), and the developmental trajectories of 55 young males with fragile X syndrome. Autistic behavior, as measured by the Childhood Autism Rating Scale, was not related to FMRP expression. However, autistic behavior was a significant predictor of both developmental status and developmental change. Boys with both autistic behavior and fragile X syndrome functioned at significantly lower levels of development and grew at significantly slower rates than those without autistic behavior. FMRP expression accounted for less variance in developmental level than did autistic behavior, and was not significantly related to slope (developmental change over time). No autistic behavior × FMRP interaction was found.

Early Development, Temperament, and Functional Impairment in Autism and Fragile X Syndrome.

We compared the developmental status, functional abilities, and temperament of 31 young boys with fragile X syndrome (FXS) who did not have autism, matched on chronological age, gender, and race, with 31 boys with autism but no FXS. Children with autism exhibited a more variable profile of development in comparison with a relatively flat profile for children with FXS. Children with autism were significantly more delayed in social skills and were rated by observers as exhibiting a greater degree of impairment in cognitive, communication, and social skills. On temperament ratings, both groups were slower to adapt, less persistent, and more withdrawing than the reference group. Boys with FXS were rated as more active than the referent group, whereas boys with autism were rated as less intense, more distractible, having a higher threshold for response, and less rhythmic than the reference group. A smaller three-group analysis compared boys with FXS, boys with autism, and boys with both FXS and autism. Children with both autism and FXS were substantially more delayed than children with autism or FXS alone.

Early developmental trajectories of males with fragile X syndrome.

Findings from a prospective longitudinal study of 46 boys with fragile X syndrome between the ages of 24 and 72 months were reported. Hierarchical linear modeling was used to construct and evaluate overall developmental trajectories and scores in five domains: Cognition, Communication, Adaptive, Motor, and Personal-Social. The children varied widely, with significant differences across individuals in both mean rate and level of performance. Overall development was significantly delayed, with a slope of .48--approximately half the rate expected for typically developing children. No differences were found in rates of growth across the five domains. Significant differences were found, however, in mean levels of performance. At every age tested, Motor and Adaptive scores were higher than Communication and Cognitive.

ADHD symptoms in children with FXS.

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.

Self-injurious behavior in young boys with fragile X syndrome

In this study, we distributed surveys to 67 families of young boys with fragile X syndrome to determine the prevalence, onset, form, function, location, and correlates of self‐injurious behavior. Fifty‐five surveys were completed (82%). The mean age of the boys at the time of the survey was 80 months (range = 20–144). Self‐injurious behavior (SIB) was reported for 58% of the participants with a mean age of onset of 31 months. The mean number of forms of self‐injury was 2 per participant. Biting was the most commonly reported form of self‐injury with the fingers and back of the hand disproportionately targeted as the most prevalent self‐injury body site. There was no linear increase in risk of SIB with age past 25 months. SIB was reported as most likely to occur following the presentation of difficult task demands or changes in routine. Significant group differences were found between overall ratings of problem behavior for boys with self‐injury compared to those without self‐injury. Groups did not differ on measures of fragile X mental retardation protein (FMRP), autism status, adaptive behavior, or age first medicated. Results are discussed in terms of future research designed to further elucidate the behavioral phenotype of fragile X syndrome.

Executive functions in young males with fragile X syndrome in comparison to mental age-matched controls: baseline findings from a longitudinal study.

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.

Variability in FMRP and early development in males with fragile X syndrome

To test the hypothesis that variability in development in fragile X syndrome is related to FMRP (the protein deficient in this syndrome expression), we studied 53 males between 23 and 98 months of age. For the entire group, which included males with either mosaism, partially methylated full mutation, and fully methylated full mutation, FMRP expression ranged from 1% to 40% and accounted for a small but significant amount of variance in level, but not rate, of total development as well as motor, social, adaptive, cognitive, and language development. For males with a fully methylated full mutation, the association was in the hypothesized direction, but not statistically significant. Findings support the hypothesized relationship between FMRP and individual capabilities but suggest that other factors also play a major role.