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

Abstract

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.

Monitoring the prevalence of severe intellectual disability in children across Europe: feasibility of a common database

“…Including adaptive behaviour testing in the diagnosis, as achieved systematically only in Iceland, may decrease the number of falsely positive cases (thus wrongly considered with severe intellectual disability). 20,21 In spite of this, the highest prevalence was found in Iceland. This may be explained by the fact that the adaptive behaviour scores appear to be more important for those with higher intellectual scores, that is for those with mild intellectual disability, than for those with severe intellectual disability.…”

Modeling fragile X syndrome in the <i>Fmr1</i> knockout mouse

“…The variability in the strength and direction of phenotypic differences observed in the Fmr1 KO mouse may at first seem unsettling and worthy of discarding the model altogether. However, the heterogeneity of FXS is such that affected individuals exhibit a range of cognitive impairments, with affected males presenting with mild to severe cognitive symptoms (162,209). This poses a challenge for FXS animal models, but it also might be considered a strength.…”

“…IQ scores decrease over time, which is likely a result of delayed development in individuals with FXS (160,161). Novel approaches to intelligence testing have found that traditional IQ tests can be modified to reveal subtle differences within this select population (162). Starting with the Dutch-Belgium Fragile X Consortium, many researchers have conducted thorough characterizations of Fmr1 KO mice to compare their phenotypes to the intellectual disabilities displayed by individuals with FXS.…”

Fragile X syndrome – a common disease rarely diagnosed

“…Their IQs tend to decline with age during childhood, and this is not the result of regression, but rather the failure to keep pace with the normal rate of intellectual development [10]. Intellectual functioning is defined as IQ.…”

“…Intellectual functioning is defined as IQ. This assessment is obtained through standardized, individually administered intelligence tests [10]. A major limitation of these tests is that they do not typically measure IQ below 40 or 50 [10], and previous observations in the literature have reported that only 15% of all males with FXS have IQ greater than or equal to 70% [7].…”