Girls with fragile X show impairments in cognitive function, academic performance

No significant differences from controls noted in adaptive behavior

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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School-age girls with fragile X syndrome show significantly poorer cognitive function and academic performance relative to age- and IQ-matched girls without the disease, a new U.S. study reports.

The fragile X group showed impairments in several cognitive skills, including nonverbal reasoning, visual pattern recognition, attention, memory, and math skills.

However, there were no significant differences in terms of adaptive behavior, or the age-appropriate behaviors necessary for people to meet their own needs and deal with the demands of their environment.

The performance of the girls with fragile X will continue to be monitored, which “may help clarify the trajectory of skill development in girls with FRX [fragile X syndrome] during childhood and adolescence,” and develop “more targeted interventions to maximize long-term outcomes and quality of life in this vulnerable population,” the researchers wrote.

The study, “Cognition, academic achievement, and adaptive behavior in school-aged girls with fragile X syndrome,” was published in the journal Research In Developmental Disabilities.

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Fragile X syndrome is the most common cause of inherited intellectual disability, generally characterized by an IQ, or intelligence quotient, of about 70 or below, compared with an average of about 100 in cognitively typical people.

Fragile X is caused by a genetically inherited deficiency of the FMRP protein, which controls the production of other proteins involved in nerve cell communication. This deficiency results in moderate to severe intellectual, behavioral, and learning challenges in males.

“Females with FXS typically display a milder cognitive [profile] than males, despite experiencing significant developmental, behavioral, and social-emotional issues,” the researchers wrote.

So far, most studies in fragile X have focused either on males or a mix of male and female patients. Far fewer studies have focused exclusively on female patients, particularly during school years.

Cognitive-behavioral profile compared

Here, a team of researchers at the Stanford School of Medicine compared the cognitive-behavioral profile of school-age girls with fragile X with that of healthy girls matched for age and verbal IQ, or spoken language skills, who served as controls.

“This is different from most previous studies of girls with FXS, which included a comparison group of either typically developing peers or full scale IQ-matched peers (which has limitations, given that verbal IQ may be a better representation of overall cognitive abilities among individuals with FXS),” the team wrote.

The study included 55 girls with fragile X (mean age 10.6 years) and 42 girls in the control group (mean age 10.4 years).

Based on previous research, the researchers hypothesized that girls with fragile X would exhibit significant differences in cognitive function, including executive function, academic achievements, and adaptive behavior relative to their healthy peers. Executive function refers to cognitive abilities needed for self-control, flexible thinking, and coordinating behavior, emotion, and cognitive capabilities.

Cognitive function was evaluated with the Differential Abilities Scales, second edition, which measures several cognitive abilities important for learning. Executive function was assessed using the National Institutes of Health Toolbox Cognition Battery, which evaluates features including attention, episodic memory, and language.

In agreement with their hypothesis, girls with fragile X showed significantly poorer cognitive performance across many of the subclasses evaluated in the Differential Abilities Scales test  relative to the control group. This included poorer ability to recognize and imitate wooden block constructions, solve visual puzzles, explain how three things or concepts go together, and identify sequential patterns in pictures or geometric figures, or common rules in numerical relationships.

Impairments in executive function

The fragile X group also had significant impairments in executive function, namely in attention, inhibitory control (self-controlled behavior), and working memory, or the temporary storage and manipulation of information needed for complex cognitive tasks.

Academic achievements also were significantly poorer among girls with fragile X, specifically in mathematics, as evaluated by the standard Kaufman Test of Educational Achievement, third edition brief form. No significant differences were found for the test’s reading domain.

Adaptive behavior, assessed by the Vineland Adaptive Behavior Scales, third edition, showed no significant differences between the groups.

The researchers then assessed how different parameters correlated with each other in each group. Higher verbal skills and nonverbal reasoning was significantly associated with better academic achievement (both math and reading) in both groups. A similar link was seen between higher verbal ability and higher adaptive functioning.

Higher nonverbal reasoning scores showed a significant correlation with better adaptive behavior in the fragile X group alone. Better nonverbal reasoning was more strongly linked to better socialization and daily living skills in girls with fragile X than in the controls.

A higher capacity to identify visual and spatial relationships among objects was significantly associated with better adaptive behavior and academic achievements in the fragile X group. In the control group, these spatial abilities showed a significant link only with math-related academic achievements.

Only in fragile X girls was a better working memory linked to better adaptive behavior and academic achievement. The same was seen regarding better attention and inhibitory control being associated with better socialization, communication skills, and academic achievement in the fragile X group.

“As predicted, our … analysis of school-aged girls with FXS and age- and verbal IQ-matched peers revealed significantly poorer performance for the FXS group on standardized measures of overall cognition, executive function, and academic achievement,” the researchers concluded.