Longitudinal changes in intellectual development in children with Fragile X syndrome

Abstract

Structural equation modeling (SEM) was used to examine the development of intellectual functioning in 145 school-age pairs of siblings. Each pair included one child with Fragile X syndrome (FXS) and one unaffected sibling. All pairs of children were evaluated on the Wechsler Intelligence Scale for Children-Third Edition (WISC-III) at time 1 and 80 pairs of children received a second evaluation at time 2 approximately 4 years later. Compared to their unaffected siblings, children with FXS obtained significantly lower percentage correct scores on all subtests of the WISC at both time points. During the time between the first and second assessments, the annual rate of intellectual development was approximately 2.2 times faster in the unaffected children compared to the children with FXS. Levels of the fragile X mental retardation protein (FMRP) were highly associated with intellectual ability scores of the children with FXS at both time points (r=0.55 and 0.64 respectively). However, when gender, age, and the time between assessments were included as covariates in the structural equation model, FMRP accounted for only 5% of the variance in intellectual ability scores at time 1 and 13% of the variance at time 2. The results of this study suggest that slower learning contributes to the low and declining standardized IQ scores observed in children with FXS.

Fig. 1

Measurement model illustrating the factor structure for the intellectual ability factors in children with FXS and their unaffected siblings. E1 to E8 are error terms for the scales. Two-headed arrows represent correlations, and one-headed arrows represent directional effects. Factor loadings are placed next to each factor indicator. R² values for each indicator can be obtained by squaring the standardized factor loadings. Only significant correlations are shown. *p<0.05; **p<0.01

Fig. 2

Structural equation model of the effect of GENDER, FMRP, FXS AGE, SIBLING AGE, and INTERVAL on the intellectual ability factors. E1 to E8 are the error terms for the factor indicators, while E9 to E12 are the error terms for the factors. E0 is the error term for FMRP. Unstandardized beta coefficients are indicated next to one-headed arrows, R² values are indicated next to the dependent variables, and correlations are indicated next to two-headed arrows. *p<0.05; **p<0.01