A solution to limitations of cognitive testing in children with intellectual disabilities: The case of fragile X syndrome

Medical Investigation of Neurodevelopmental Disorders (M.I.N.D.), Institute, University of California-Davis Medical Center, 2825 50th Street, Sacramento, CA 95817, USA.
Journal of Neurodevelopmental Disorders (Impact Factor: 3.27). 03/2009; 1(1):33-45. DOI: 10.1007/s11689-008-9001-8
Source: PubMed


Intelligence testing in children with intellectual disabilities (ID) has significant limitations. The normative samples of widely used intelligence tests, such as the Wechsler Intelligence Scales, rarely include an adequate number of subjects with ID needed to provide sensitive measurement in the very low ability range, and they are highly subject to floor effects. The IQ measurement problems in these children prevent characterization of strengths and weaknesses, poorer estimates of cognitive abilities in research applications, and in clinical settings, limited utility for assessment, prognosis estimation, and planning intervention. Here, we examined the sensitivity of the Wechsler Intelligence Scale for Children (WISC-III) in a large sample of children with fragile X syndrome (FXS), the most common cause of inherited ID. The WISC-III was administered to 217 children with FXS (age 6-17 years, 83 girls and 134 boys). Using raw norms data obtained with permission from the Psychological Corporation, we calculated normalized scores representing each participant's actual deviation from the standardization sample using a z-score transformation. To validate this approach, we compared correlations between the new normalized scores versus the usual standard scores with a measure of adaptive behavior (Vineland Adaptive Behavior Scales) and with a genetic measure specific to FXS (FMR1 protein or FMRP). The distribution of WISC-III standard scores showed significant skewing with floor effects in a high proportion of participants, especially males (64.9%-94.0% across subtests). With the z-score normalization, the flooring problems were eliminated and scores were normally distributed. Furthermore, we found correlations between cognitive performance and adaptive behavior, and between cognition and FMRP that were very much improved when using these normalized scores in contrast to the usual standardized scores. The results of this study show that meaningful variation in intellectual ability in children with FXS, and probably other populations of children with neurodevelopmental disorders, is obscured by the usual translation of raw scores into standardized scores. A method of raw score transformation may improve the characterization of cognitive functioning in ID populations, especially for research applications.

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    • "Alternatives to the RIQ are available. For example, Fragile X researchers have accounted for floor effects in some common intelligence tests by developing alternative deviation scoring systems (Hessl et al., 2009; Sansone et al., 2014), though this approach has not yet been applied to preschool testing. In the context of research studies, a predicted score might be used (Whitaker & Gordon, 2012). "
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    ABSTRACT: Estimates of intelligence in young children with neurodevelopmental disorders are critical for making diagnoses, in characterizing symptoms of disorders, and in predicting future outcomes. The limitations of standardized testing for children with developmental delay or cognitive impairment are well known: Tests do not exist that provide developmentally appropriate material along with norms that extend to the lower reaches of ability. Two commonly used and interchanged instruments are the Mullen Scales of Early Learning (MSEL), a test of developmental level, and the Differential Ability Scales, second edition (DAS-II), a more traditional cognitive test. We evaluated the correspondence of contemporaneous MSEL and the DAS-II scores in a mixed sample of children aged 2-10 years with autism spectrum disorder (ASD), non-ASD developmental delays, and typically developing children across the full spectrum of cognitive ability. Consistent with published data on the original DAS and the MSEL, scores on the DAS-II and MSEL were highly correlated. However, curve estimation revealed large mean differences that varied as a function of the child's cognitive ability level. We conclude that interchanging MSEL and DAS-II scores without regard to the discrepancy in scores may produce misleading results in both cross-sectional and longitudinal studies of children with and without ASD, and, thus, this practice should be implemented with caution.
    Child Neuropsychology 04/2015; DOI:10.1080/09297049.2015.1020775 · 2.42 Impact Factor
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    • "All children but one were in the lower end of the standard scores, indicating a floor effect. This effect is well-known in research with intellectually disabled persons (e.g., Carlier & Ayoun, 2007; Carlier & Roubertoux, 2014; Hessl et al., 2009). It arises with most intelligence tests (Reynolds & Kamphaus, 2003), which therefore typically fail to detect valid differences in the lower ranges. "
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    ABSTRACT: People spontaneously use faces to make inferences about other's personality traits or abilities, which generally lead to invalid conclusions. Here, we show first evidence that perceived variations in the facial appearance of 20 children with trisomy 21 (t21) influence how they are perceived in terms of intelligence (or intellectual disability), the more “trisomic” faces being rated as less intelligent (or more intellectually disabled). Despite high degrees of inter-rater agreement (80 raters), these inferences were unrelated to individuals’ actual test scores which were also unrelated to perceived facial appearance. All these findings indicate that social inferences about intelligence based on facial appearance are unreliable even in groups characterized by a genetic disorder such as t21.
    Research in Developmental Disabilities 12/2014; 35(12):3598-3605. DOI:10.1016/j.ridd.2014.09.003 · 3.40 Impact Factor
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    • "Typical physical features include: macrocephaly, long face with prominent ears, macroorchidism, and hyperextensible joints [Gallagher and Hallahan, 2012]. The cognitive phenotype is characterized by moderate to severe ID in males [Hessl et al., 2009]. In addition, individuals with FXS exhibit many behavioral problems such as attention-deficit hyperactivity disorder (ADHD) features, anxiety, and aggressiveness, which make daily living difficult for both impaired individuals and caregivers. "
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    ABSTRACT: Fragile X syndrome (FXS) results from dynamic mutations leading ultimately to the absence of expression of the Fragile X Mental Retardation Protein (FMRP). It is characterized by synaptic upregulated protein synthesis and immature dendritic spines associated with altered brain plasticity and cognitive functions. Recent work in Fmr1 knockout mice has shown that lovastatin, an inhibitor of Ras-ERK1/2, normalized hippocampus protein synthesis. We hypothesize that lovastatin, as a disease-modifying drug, would counterweigh the absence of FMRP and improve behavior. Here we report a phase I study to assess the safety and efficacy of lovastatin in individuals with FXS. A total of 15 patients (13 males, 6–31 years old) were treated with escalating doses of lovastatin (up to 40 mg) for three months. Their behavior were assessed before and after treatment using the Aberrant Behavioral Checklist—Community (ABC-C) total score (primary outcome), as well as domains of the FXS validated version of the ABC-C (secondary outcomes). The treatment was well tolerated and minimal side effects were reported. Significant improvement in the primary outcome (P < 0.005), as well as in secondary outcomes, were observed in the majority of the subjects (12/15). We think that long-term sustained treatment with diseased-modifying drugs would be necessary in order to improve behavior and ultimately learning. Lovastatin, well known for its long-term security profile, would be a good candidate for that purposes. Our study showing reassuring safety data along with potential functional benefit emphasizes the need of a placebo-controlled trial to ascertain lovastatin efficacy in FXS individuals. © 2014 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 11/2014; 164A(11). DOI:10.1002/ajmg.a.36750 · 2.16 Impact Factor
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