Penny Mirrett

Autistic behavior in children with fragile X syndrome: Prevalence, stability, and the impact of FMRP

We examined autistic behavior in a cross‐sectional sample of 179 children with fragile X syndrome (FXS) and a longitudinal subset of 116 children using the Childhood Autism Rating Scale (CARS) to (a) determine a prevalence of autistic behavior in FXS, (b) examine the stability of autistic ratings over time, and (c) assess the association between the fragile X mental retardation protein (FMRP) and autistic behavior. Approximately 21% of the sample of 129 children (25.9% of boys) scored at or above the cutoff for autism. CARS scores increased slowly, yet significantly, over time, and low levels of FMRP were associated with higher mean levels of autistic behavior as measured by the CARS.

Receptive and Expressive Communication Development of Young Males With Fragile X Syndrome

We prospectively examined the developmental trajectories of receptive and expressive communication skills of 39 young males, 20 to 86 months of age, with fragile X syndrome. Eight showed features characteristic of autism. Children were tested one to three times using a standardized language test. They showed marked delays in language development, but substantial individual variability. Participants acquired expressive language skills more slowly than receptive language over time, gaining receptive language at about half the rate expected for typically developing children and expressive language at one third the rate. Both cognitive skills and autistic characteristics of the young males with fragile X syndrome related to receptive and expressive communication development, but neither predicted the discrepancies between expressive and receptive language acquisition over time.

Executive functions in young males with fragile X syndrome in comparison to mental age-matched controls: baseline findings from a longitudinal study.

The performance of 54 boys with fragile X syndrome (FXS), ages 7 to 13 years, was compared to that of a group of typically developing boys who were matched on mental age (MA) and ethnicity across multiple measures of executive function (EF). Boys with FXS varied in their ability to complete EF measures, with only 25.9% being able to complete a set-shifting task and 94.4% being able to complete a memory for word span task. When compared to the control group, and controlling for MA and maternal education, boys with FXS showed significant deficits in inhibition, working memory, cognitive flexibility/set-shifting, and planning. No group differences were observed in processing speed. Mental age significantly impacted performance on working memory, set-shifting, planning, and processing speed tasks for both groups. In boys with FXS, MA significantly predicted performance on working memory and set-shifting tasks. Our findings suggest that deficits in EF in boys with FXS are not solely attributable to developmental delays but, rather, present as a true array of neurocognitive deficits.

Developmental trajectories and correlates of sensory processing in young boys with fragile X syndrome.

Background and Purpose: No longitudinal study on sensory processing in children with fragile X syndrome (FXS) exists. This study examined developmental trajectories and correlates of sensory processing from infancy through preschool years in 13 boys with FXS. Method: Participants were assessed using observational and parent-report measures 2–6 times between 9 and 54 months of age. Results: Over time, an increasing proportion of boys displayed sensory processing that differed significantly from test norms. Observational measures were more sensitive than parent-reports early in infancy. Age and developmental quotient significantly predicted levels of hyporesponsiveness; there was a trend for hyperresponsiveness to increase with age. Baseline physiological and biological measures were not predictive. Conclusions: Sensory processing problems are observable early and grow increasingly problematic from infancy through the preschool ages. Early identification and intervention may attenuate long-term difficulties for children with FXS.

Adaptive Behavior in Children With Fragile X Syndrome

Adaptive behavior over time in 70 children with fragile X syndrome, ages 1 to 12 years, was examined using the Vineland Adaptive Behavior Scales. With a mean of 4.4 assessments per child, adaptive behavior skills increased steadily and gradually over time. Children with less autistic behavior and higher percentages of FMPR expression showed better performance on all areas of adaptive behavior. Children without autistic behavior displayed higher scores and rates of growth on the Daily Living Skills domain, with the lowest scores in Socialization. Comparison to Brief IQs indicate that children with fragile X syndrome display nonverbal IQs superior to their adaptive behavior when they are below age 10 but that these skills seem to converge as they get older.

Mapping nonverbal IQ in young boys with fragile X syndrome

This study examines the developmental changes in nonverbal intellectual functioning evident in males with fragile X syndrome (FXS) measured by the Leiter International Performance Scales‐Revised (Leiter‐R). The Leiter‐R provides both IQ scores and associated growth scores which permit the examination of both age‐based IQ scores and overall intellectual growth. Participants were 45 males with full mutation FXS and ranged in age from 4.0 to 13.8 years. Each child was assessed annually using the Leiter‐R as part of a larger longitudinal battery for an average of 3.5 assessments per child and a range of 2–6 assessments, representing a total of 156 assessment occasions. Longitudinal analyzes of Leiter scores consisted primarily of hierarchical linear modeling, with the impact of chronological age, maternal education, fragile X mental retardation 1 protein (FMRP), autistic behaviors also being assessed. Findings revealed a significant linear decline in nonverbal IQ scores, with no effects of maternal education, autistic behaviors, or FMRP on mean level or rate of change in IQ scores over time. The decline slowed significantly around 8 years of age, but scores continued to decline into the 12th year of age. In contrast, a significant linear increase was observed in Leiter‐R growth scores, which was negatively influenced by autistic behaviors. The rate of increase did not change over time, and neither mean level nor rate of increase was influenced by maternal education or FMRP levels. These findings suggest that declines in IQ are the result of steady, but suboptimal intellectual growth, rather than a true deterioration in overall intellectual functioning.

Developmental screening and detection of developmental delays in infants and toddlers with fragile X syndrome.

Three developmental screening tests (the Denver-II, Battelle Developmental Inventory Screening Test, and Early Language Milestone Scale-2) were administered to 18 infants and toddlers (13 boys and 5 girls) with confirmed diagnoses of fragile X syndrome as part of a comprehensive developmental assessment at 9, 12, and 18 months of age. The Denver-II identified delays for 10 of 11 boys at 9 months of age and the Denver-II and the Early Language Milestone Scale-2 identified delays in 100% of the boys at 12 and 18 months. The Battelle Developmental Inventory Screening Test identified delays in 75% of the children at 12 and 18 months. When compared with more comprehensive developmental tests (Mullen Scales of Early Learning and Receptive-Expressive Emergent Language Scale-2), the screening tests concurred at least 76% of the time at the 12- and 18-month assessments. These results indicate that developmental delays could be detected in most children with fragile X syndrome through routine developmental screening by the age of 9 to 12 months.

Memory Skills of Boys With Fragile X Syndrome

Multiple aspects of memory were examined in 42 boys with fragile X syndrome and a comparison group of 42 typically developing boys matched on MA. Working memory, incidental memory, and deliberate memory were assessed with a battery that included both free-recall and recognition tasks. Findings indicated that boys with fragile X syndrome performed more poorly than their matches on most measures. The exception was free recall, in which their accuracy was equal to that of the control participants. Results from analyses of a subset of boys with fragile X syndrome who exhibit characteristics of autism and their MA matches, though preliminary, support the conclusion that memory deficits are especially marked in boys who have fragile X syndrome and evidence autistic behaviors.

Research on fragile X syndrome and autism: Implications for the study of genes, environments, and developmental language disorders

Contents: M.L. Rice, S.F. Warren, Preface. M.L. Rice, S.F. Warren, Introduction. Part I:Phenotypes of Language Impairments Within Clinical Diagnoses. C. Lord, S. Risi, A. Pickles, Trajectory of Language Development in Autistic Spectrum Disorders. H. Tager-Flusberg, Do Autism and Specific Language Impairment Represent Overlapping Language Disorders? J.B. Tomblin, X. Zhang, A. Weiss, H. Catts, S.E. Weismer, Dimensions of Individual Differences in Communication Skills Among Primary Grade Children. L. Abbeduto, M.M. Murphy, Language, Social Cognition, Maladaptive Behavior, and Communication in Down Syndrome and Fragile X Syndrome. A. Zukowski, Investigating Knowledge of Complex Syntax: Insights From Experimental Studies of Williams Syndrome. D.B. Bailey, Jr., J.E. Roberts, S.R. Hooper, D.D. Hatton, P.L. Mirrett, J.E. Roberts, J.M. Schaaf, Research on Fragile X Syndrome and Autism: Implications for the Study of Genes, Environments, and Developmental Language Disorders. Part II:Investigating Language Impairments Across Diagnostic Categories. C.B. Mervis, Cross-Etiology Comparisons of Cognitive and Language Development. S.F. Warren, Intervention as Experiment. M.L. Rice, Growth Models of Developmental Language Disorders. C. Phillips, Linguistics and Linking Problems. Part III:Neural, Genetic, and Behavioral Elements of Inherited Factors. R-A. Muller, Genes, Language Disorders, and Developmental Archaeology: What Role Can Neuroimaging Play? S.D. Smith, Localization and Identification of Genes Affecting Language and Learning. C.A. Morris, Genotype-Phenotype Correlations: Lessons From Williams Syndrome Research. Part IV:Research Action Steps for the Short and Long Term. P. McCardle, J. Cooper, Next Steps in the Study of Genetics and Language Disorders.