Longitudinal changes in cognitive and adaptive behavior in fragile X females: A prospective multicenter analysis

Abstract

In prospective studies of young, fragile X [fra(X)] males with the full mutation, cognitive abilities (IQ scores) and adaptive behavior levels (DQ scores) declined in most subjects tested. Little is known about longitudinal changes in IQ and DQ scores in young fra(X) females, although one earlier retrospective study showed declines in IQ scores in 8 of 11 subjects. To examine fra(X) females prospectively, we tested and retested 13 females with the full mutation, age 4 to 15 years. Nine were tested and retested in North America, and four were evaluated at the Catholic University in Leuven, Belgium. Cognitive abilities of North American females were measured using the Stanford-Binet 4th Edition. Adaptive behavior levels were ascertained from the Vineland Adaptive Behavior Scales. For Belgians, test-retest scores from the Wechsler Intelligence Scales for Children-Revised were used. Subjects were subsequently separated into two age cohorts: those tested initially before age 7 years and those tested initially after age 7 years. Compared with young males with the full mutation and of the same age, females expectedly display a wider range of IQ scores. Test-retest IQ scores showed statistically significant decreases (P < 0.03). Analysis of individual test-retest scores indicate that declines in eight females were statistically significant. Adaptive behavior scores were available only for North American females. Five of nine (55%) showed significant declines in DQ. Like young males with the full mutation, all females with the full mutation attained higher adaptive behavior levels than cognitive scores, i.e., DQ > IQ.

FMR1 gene and fragile X syndrome

“…Early reports also noted heterozygous females whose IQ scores declined [Hagerman and Smith, 1983]. Although most females with fragile X show decreases in IQ scores, their declines are not as steep, nor is the proportion of those affected as high as the proportion of males with the mutation [Fisch et al, 1999a]. Adaptive behavior scores also reflect a broader range of expression and a milder phenotype.…”

Biological and environmental contributions to adaptive behavior in fragile X syndrome

“…Given the previous evidence for the influences of FMRP and IQ on adaptive behavior [Dykens et al, 1996; Fisch et al, 1996; Fisch et al, 1999a], it was predicted that age, IQ, and FMRP (in the fragile X group only) would account for a significant portion of the variance in adaptive behavior. Secondly, though it has not been previously investigated in children with fragile X, we predicted that above and beyond the contribution of IQ and FMRP, characteristics of the home environment and parental psychological health would also play a significant role in the children's adaptive behavior.…”

“…Because fragile X is an X chromosome‐linked syndrome, boys with fragile X generally present a more severe array of symptoms than do girls. Though girls with fragile X can also display mental retardation, learning disabilities, inattention, social problems, and physical characteristics, these symptoms are often less severe than those demonstrated by boys [Hagerman et al, 1992; Rousseau, 1994; Fisch et al, 1999a]. Much of what has been published about the link between the genotype of children with fragile X and their degree of neurobehavioral functioning is based on direct or indirect measures of the amount of fragile X protein, FMRP, produced [Reiss et al, 1995b; Lachiewicz et al, 1996; Merenstein et al, 1996; Tassone et al, 1999].…”

Family environment and cognitive abilities in girls with fragile‐X syndrome

“…These include difficulty in abstract reasoning, perseveration and tangential language (Goldson & Hagerman 1992). A developmental decline in IQ, which can usually be observed between 3 and 15 years, has also been observed in children with the fragile X mutation (Fisch et al 1999). While children with FXS often have cognitive impairment, they also exhibit relative strengths in vocabulary skills and receptive language (Goldson & Hagerman 1992).…”