The development of adaptive behaviour in toddlers and preschoolers with fragile X versus autism

McCary, Lindsay M.; Machlin, Laura; Roberts, Jane

doi:10.1179/2047387713y.0000000016

Cited by 7 publications

(6 citation statements)

References 26 publications

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“…Several recent studies have documented the extent to which standard scores on the Vineland-II may deviate relative to the normative data at particular age bands in FXS. For example, in a cross-sectional study of boys with FXS, standard scores on the Vineland-II declined between 1 and 4 points per year depending on the subdomain [ 47 ]. Similarly, in a large-scale longitudinal study involving 275 males and females with FXS, aged 2–18 years, Klaiman and colleagues reported that standard scores for males declined by approximately 3.3 points per year on average on the Vineland-II Composite, by 4.5 points per year on the Daily Living Skills domain, by 3.5 points per year on the Communication domain, and by 2.8 points per year on the Socialization domain [ 29 ].…”

Section: Cognitive Measuresmentioning

confidence: 99%

Updated report on tools to measure outcomes of clinical trials in fragile X syndrome

Budimirović

Berry‐Kravis

Erickson

et al. 2017

J Neurodevelop Disord

131

158

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ObjectiveFragile X syndrome (FXS) has been the neurodevelopmental disorder with the most active translation of preclinical breakthroughs into clinical trials. This process has led to a critical assessment of outcome measures, which resulted in a comprehensive review published in 2013. Nevertheless, the disappointing outcome of several recent phase III drug trials in FXS, and parallel efforts at evaluating behavioral endpoints for trials in autism spectrum disorder (ASD), has emphasized the need for re-assessing outcome measures and revising recommendations for FXS.MethodsAfter performing an extensive database search (PubMed, Food and Drug Administration (FDA)/National Institutes of Health (NIH)’s www.ClinicalTrials.gov, etc.) to determine progress since 2013, members of the Working Groups who published the 2013 Report evaluated the available outcome measures for FXS and related neurodevelopmental disorders using the COSMIN grading system of levels of evidence. The latter has also been applied to a British survey of endpoints for ASD. In addition, we also generated an informal classification of outcome measures for use in FXS intervention studies as instruments appropriate to detect shorter- or longer-term changes.ResultsTo date, a total of 22 double-blind controlled clinical trials in FXS have been identified through www.ClinicalTrials.gov and an extensive literature search. The vast majority of these FDA/NIH-registered clinical trials has been completed between 2008 and 2015 and has targeted the core excitatory/inhibitory imbalance present in FXS and other neurodevelopmental disorders. Limited data exist on reliability and validity for most tools used to measure cognitive, behavioral, and other problems in FXS in these trials and other studies. Overall, evidence for most tools supports a moderate tool quality grading. Data on sensitivity to treatment, currently under evaluation, could improve ratings for some cognitive and behavioral tools. Some progress has also been made at identifying promising biomarkers, mainly on blood-based and neurophysiological measures.ConclusionDespite the tangible progress in implementing clinical trials in FXS, the increasing data on measurement properties of endpoints, and the ongoing process of new tool development, the vast majority of outcome measures are at the moderate quality level with limited information on reliability, validity, and sensitivity to treatment. This situation is not unique to FXS, since reviews of endpoints for ASD have arrived at similar conclusions. These findings, in conjunction with the predominance of parent-based measures particularly in the behavioral domain, indicate that endpoint development in FXS needs to continue with an emphasis on more objective measures (observational, direct testing, biomarkers) that reflect meaningful improvements in quality of life. A major continuous challenge is the development of measurement tools concurrently with testing drug safety and efficacy in clinical trials.

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Section: Cognitive Measuresmentioning

confidence: 99%

Updated report on tools to measure outcomes of clinical trials in fragile X syndrome

Budimirović

Berry‐Kravis

Erickson

et al. 2017

J Neurodevelop Disord

131

158

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“…Down syndrome (DS) and fragile X syndrome (FXS) are two neurogenetic disorders with distinct genetic etiologies. Both DS and FXS have a phenotype predominantly characterized by impairments in adaptive behavior and moderate ID, although there is a range of ID from mild to more severe (Loesch, Huggins, & Hagerman, ; McCary, Machlin, & Roberts, ). Despite our current knowledge on adaptive functioning in these populations, the bulk of research has focused on school‐age and older samples, with no cross‐syndrome comparisons examining adaptive behavior during early development.…”

Section: Introductionmentioning

confidence: 99%

“…Extant work indicates age‐related changes in adaptive skills in FXS, and areas of competence and impairment differ depending on developmental period and measurement. For example, research utilizing raw scores evidences adaptive skill growth through age 10, with plateaus or slight declines thereafter (Dykens et al, ; Hahn et al, ), while studies examining standard scores show declines across time beginning in toddlerhood (McCary et al, ; Klaiman et al, ). In terms of general areas of competence and impairment, individuals with FXS tend to show greater abilities in daily living compared to socialization and communication (Fisch et al, ; Hatton et al, ).…”

Section: Introductionmentioning

confidence: 99%

Adaptive behavior in infants and toddlers with Down syndrome and fragile X syndrome

Will

Caravella

Hahn

et al. 2018

American J of Med Genetics Pt B

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Individuals with Down syndrome (DS) experience deficits across all domains of adaptive functioning, however little is known about the emergence and age-related changes of these impairments compared to other neurogenetic disorders with similar intellectual disability impairments, such as fragile X syndrome (FXS). Adaptive behavior is key for optimal functioning in these populations. Participants aged 5-45 months comprised three age-matched groups, DS (n = 64), FXS (n = 69), and typically developing controls (TD; n = 69). Adaptive behavior was measured on the Vineland Adaptive Behavior Scales-II. Regressions were used to examine adaptive behavior in a cross-sectional design across age. DS infants and toddlers evidenced deficits across all areas of adaptive behaviors compared to the age-matched TD group, with clear impairments present in the first year of life. Motor skills were the area of greatest weakness in children with DS with significant impairment evident at 12 months of age that remained low through 3 years. Compared to age-matched children with FXS, children with DS showed initially lower standard scores at 12 months of age, but slower declines in standard scores across age, resulting in less impaired functioning at 36 months. This is the first study to compare adaptive behavior in infants and toddlers with DS to FXS, and demonstrate the phenotypic specificity of adaptive profiles in this diagnostic group. These findings provide evidence that adaptive behavior should be a major target of intervention in children with FXS and DS, and that these differences are potentially driven by unique etiologies attributable to each disorder.

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“…Development is highly impacted by FXS; most individuals with FXS fall in the moderate range of intellectual disabilities (Bailey, Raspa, Olmsted, & Holiday, 2008; Roberts, Mirrett, P., & Burchinal, 2001; Roberts, McCary, Shinkareva, & Bailey, 2016). Adaptive behaviors are also impaired, with growth significantly slower than age-based expectations (Hatton et al, 2003; McCary, Machlin, & Roberts, 2013). In addition to cognitive and adaptive deficits, the core behavioral phenotype of FXS includes symptoms such as inattention, hyperactivity, and impulsivity (Sullivan et al, 2006), as well as a number of autistic symptoms, such as poor eye contact, stereotypic behaviors, atypical sensory responses, and social-communication impairments (Hatton et al, 2006; Kaufmann et al, 2004; Klusek, Martin, & Losh, 2014a).…”

Section: Fragile X Syndromementioning

confidence: 99%

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

Robinson

Klusek

Poe

et al. 2018

American Journal on Intellectual and Developmental Disabilities

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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.

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The development of adaptive behaviour in toddlers and preschoolers with fragile X versus autism

Cited by 7 publications

References 26 publications

Updated report on tools to measure outcomes of clinical trials in fragile X syndrome

Updated report on tools to measure outcomes of clinical trials in fragile X syndrome

Adaptive behavior in infants and toddlers with Down syndrome and fragile X syndrome

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

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