Anne C. Wheeler

Adaptive Behavior in Children With Fragile X Syndrome

Adaptive behavior over time in 70 children with fragile X syndrome, ages 1 to 12 years, was examined using the Vineland Adaptive Behavior Scales. With a mean of 4.4 assessments per child, adaptive behavior skills increased steadily and gradually over time. Children with less autistic behavior and higher percentages of FMPR expression showed better performance on all areas of adaptive behavior. Children without autistic behavior displayed higher scores and rates of growth on the Daily Living Skills domain, with the lowest scores in Socialization. Comparison to Brief IQs indicate that children with fragile X syndrome display nonverbal IQs superior to their adaptive behavior when they are below age 10 but that these skills seem to converge as they get older.

Mapping nonverbal IQ in young boys with fragile X syndrome

This study examines the developmental changes in nonverbal intellectual functioning evident in males with fragile X syndrome (FXS) measured by the Leiter International Performance Scales‐Revised (Leiter‐R). The Leiter‐R provides both IQ scores and associated growth scores which permit the examination of both age‐based IQ scores and overall intellectual growth. Participants were 45 males with full mutation FXS and ranged in age from 4.0 to 13.8 years. Each child was assessed annually using the Leiter‐R as part of a larger longitudinal battery for an average of 3.5 assessments per child and a range of 2–6 assessments, representing a total of 156 assessment occasions. Longitudinal analyzes of Leiter scores consisted primarily of hierarchical linear modeling, with the impact of chronological age, maternal education, fragile X mental retardation 1 protein (FMRP), autistic behaviors also being assessed. Findings revealed a significant linear decline in nonverbal IQ scores, with no effects of maternal education, autistic behaviors, or FMRP on mean level or rate of change in IQ scores over time. The decline slowed significantly around 8 years of age, but scores continued to decline into the 12th year of age. In contrast, a significant linear increase was observed in Leiter‐R growth scores, which was negatively influenced by autistic behaviors. The rate of increase did not change over time, and neither mean level nor rate of increase was influenced by maternal education or FMRP levels. These findings suggest that declines in IQ are the result of steady, but suboptimal intellectual growth, rather than a true deterioration in overall intellectual functioning.

Associated features in females with an FMR1 premutation

Changes in the fragile X mental retardation 1 gene (FMR1) have been associated with specific phenotypes, most specifically those of fragile X syndrome (FXS), fragile X tremor/ataxia syndrome (FXTAS), and fragile X primary ovarian insufficiency (FXPOI). Evidence of increased risk for additional medical, psychiatric, and cognitive features and conditions is now known to exist for individuals with a premutation, although some features have been more thoroughly studied than others. This review highlights the literature on medical, reproductive, cognitive, and psychiatric features, primarily in females, that have been suggested to be associated with changes in the FMR1 gene. Based on this review, each feature is evaluated with regard to the strength of evidence of association with the premutation. Areas of need for additional focused research and possible intervention strategies are suggested.

Perceived Quality of Life in Mothers of Children With Fragile X Syndrome

A mixed method approach was used to explore quality of life of 101 mothers of children with fragile X syndrome. Mothers completed a self-report of personal quality of life and measures of mental health and well-being. A subset was interviewed about quality of life. The distribution of scores on the Quality of Life Inventory was similar to the norms, indicating that these mothers do not, as a whole, report a lower quality of life than does the average woman. Significant predictors of quality of life were trait hope and parenting stress. The most common positive factor was being a mother. However, they also indicated that parenting a child with fragile X presented challenges and stressors, primarily when the social environment was not supportive.

Health and economic consequences of fragile X syndrome for caregivers.

Objective: To describe the health and economic burden experienced by caregivers of individuals with fragile X syndrome (FXS) and test the assumption that burden is associated with specific dimensions of problem behavior. Methods: Three hundred fifty caregivers rated their son or daughter’s problem behavior and reported the use of medical services, caregiving time, impact on employment, financial burden, caregiver injuries, caregiver mental health, and prescription drug use. Results: The sons FXS posed a significant burden for caregivers in a number of areas. Visits to medical specialists were common for both males (5.4 per year) and females (5.1 per year). Caregivers reported 9.2 hours per day of family caregiving for males with FXS and an additional 5.5 hours of paid help. Most families reported that FXS had at least some financial impact on the family, and caregivers had to take an average of 19.4 hours from work each month to care for their child’s needs. Almost one third of the caregivers had been injured by their child at least once in the past year; when injuries occurred, the frequency was high (14.7 per year), of which 2.7 required medical care. Approximately one third of the caregivers had seen a professional for anxiety, stress, or depression during the past year, and one fourth were taking medication to help with these symptoms. Caregiver burden was highly associated with problem behavior, most commonly irritability. Conclusion: Problem behavior is a strong contributor to burden experienced by caregivers of children and adults with FXS. Clinicians should be aware of the role problem behavior plays in family adaptation and help families access appropriate medical and social support services.

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.

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.

Anxiety, attention problems, hyperactivity, and the Aberrant Behavior Checklist in fragile X syndrome

Behavior problems are a common challenge for individuals with fragile X syndrome (FXS) and constitute the primary clinical outcome domain in trials testing new FXS medications. However, little is known about the relationship between caregiver‐reported behavior problems and co‐occurring conditions such as anxiety and attention problems. In this study, 350 caregivers, each with at least one son or daughter with full‐mutation FXS, rated one of their children with FXS using the Aberrant Behavior Checklist—Community Version (ABC‐C); the Anxiety subscale of the Anxiety, Depression, and Mood Scale; and the Attention/Hyperactivity Items from the Symptom Inventories. In addition to examining family consequences of these behaviors, this study also sought to replicate psychometric findings for the ABC‐C in FXS, to provide greater confidence for its use in clinical trials with this population. Psychometric properties and baseline ratings of problem behavior were consistent with other recent studies, further establishing the profile of problem behavior in FXS. Cross‐sectional analyses suggest that selected dimensions of problem behavior, anxiety, and hyperactivity are age related; thus, age should serve as an important control in any studies of problem behavior in FXS. Measures of anxiety, attention, and hyperactivity were highly associated with behavior problems, suggesting that these factors at least coincide with problem behavior. However, these problems generally did not add substantially to variance in caregiver burden predicted by elevated behavior problems. The results provide further evidence of the incidence of problem behaviors and co‐occurring conditions in FXS and the impact of these behaviors on the family.

Public health literature review of Fragile X syndrome

OBJECTIVES: The purpose of this systematic literature review is to describe what is known about fragile X syndrome (FXS) and to identify research gaps. The results can be used to help inform future public health research and provide pediatricians with up-to-date information about the implications of the condition for individuals and their families. METHODS: An electronic literature search was conducted, guided by a variety of key words. The search focused on 4 areas of both clinical and public health importance: (1) the full mutation phenotype, (2) developmental trajectories across the life span, (3) available interventions and treatments, and (4) impact on the family. A total of 661 articles were examined and 203 were included in the review. RESULTS: The information is presented in the following categories: developmental profile (cognition, language, functional skills, and transition to adulthood), social-emotional profile (cooccurring psychiatric conditions and behavior problems), medical profile (physical features, seizures, sleep, health problems, and physiologic features), treatment and interventions (educational/behavioral, allied health services, and pharmacologic), and impact on the family (family environment and financial impact). Research gaps also are presented. CONCLUSIONS: The identification and treatment of FXS remains an important public health and clinical concern. The information presented in this article provides a more robust understanding of FXS and the impact of this complex condition for pediatricians. Despite a wealth of information about the condition, much work remains to fully support affected individuals and their families.

Aggression in fragile X syndrome

BACKGROUND Individuals with fragile X syndrome (FXS), especially men, have long been described as presenting with significant behavioural challenges. Despite this known aspect of the phenotype, there has been little research exploring the prevalence, frequency, nature or consequences of aggressive behaviour in FXS. METHODS This study used survey methodology to gather caregiver reports on the types, frequency and severity of aggressive behaviour in 774 individuals with FXS. RESULTS Based on caregiver report, nearly all (>90%) male and female individuals were reported to have engaged in some aggression over the previous 12 months, with a third of male cases and slightly fewer than 20% of female cases being described as engaging in moderate to severe aggression or being diagnosed or treated for aggression. Further, aggressive behaviours in male individuals were serious enough that 30% had caused injuries to caregivers and 22% had caused injuries to peers or friends. Sensory issues and hyperactivity were significant predictors of the frequency of aggressive acts, while sensory issues and anxiety were predictive of the severity of aggression. Traditional behaviour management techniques as well as medication was described as the most common and successful treatment options. CONCLUSIONS Aggressive behaviours are a significant concern for a subsample of both male and female individuals with FXS. Given that sensory concerns were predictive of both the frequency and the severity of aggression suggests these behaviours may be a reactive means of escaping uncomfortable situations.