Abstracts for the University of North Carolina and University of
Wisconsin Research Presentations at the 2012 International
Fragile X Conference, Miami, FL; July 25-29
Dr. Gary Martin; University of North Carolina at Chapel Hill; [email protected]
Title: Language Production over Time in Boys with Fragile X Syndrome with and without Autism
Authors: Martin, Losh, Estigarribia, Sideris
Presentation Description (family friendly track):
Language impairment is a very common characteristic of boys with fragile X syndrome (FXS), with language
production more impaired than comprehension and some evidence that individuals with co-morbid autism tend to
perform more poorly than do those with only FXS on language measures. In this study, we examined expressive
vocabulary, syntax (grammar), and pragmatic (social) language profiles over time in boys with FXS with and
without autism spectrum disorder (FXS-ASD; FXS-O), boys with Down syndrome (DS), and younger typically
developing (TD) boys. Performance was measured annually for three years with the Comprehensive Assessment of
Spoken Language (CASL; Carrow-Woolfolk, 1999). Results showed that boys with FXS-O scored higher (showed
more skill) than boys with FXS-ASD in pragmatic language. In addition, both boys with FXS-O and FXS-ASD scored
higher than boys with DS in grammar. Finally, TD boys scored higher than all other groups in vocabulary, grammar,
and pragmatic language, and also showed significantly more change over time than the other groups. Findings
suggest that expressive language skills and growth across various domains of language are more impaired in boys
with FXS than would be expected based on nonverbal mental age, and that autism status affects pragmatic
language in boys with FXS. During this session, implications for assessment and intervention will also be discussed.
Abstract
Background. Language impairment, and particularly pragmatic language difficulty, is a core characteristic of fragile
X syndrome (FXS), with evidence that language is disproportionately impaired over general cognitive abilities and
language production is more impaired than comprehension (Abbeduto, et al., 2007; Finestack, et al., 2009;
Roberts, et al., 2008; Roberts et al., 2001). FXS is also the most common known single-gene disorder associated
with a diagnosis of autism, and there is some evidence that individuals with both FXS and autism have more
impaired language than do those with only FXS (Bailey et al., 2001; Philofsky et al., 2004; Rogers, et al., 2001).
Objectives. To compare three domains of language production (vocabulary, syntax, pragmatics) over time within
and across groups of boys with FXS with and without autism spectrum disorder (FXS-ASD, FXS-O), boys with Down
syndrome (DS), and younger typically developing (TD) boys.
Methods. Thirty-one boys with FXS-O, 42 boys with FXS-ASD, 35 boys with DS, and 50 younger TD boys of similar
nonverbal mental age participated. The Antonyms, Syntax Construction, and Pragmatic Judgment subtests of the
Comprehensive Assessment of Spoken Language were administered annually over three years. Data utilized for
this study were drawn from a larger longitudinal study comparing the speech and language skills of children with
FXS, DS, and TD.
Results. Between- and within-group differences were examined using a hierarchical linear model (HLM). Nonverbal
mental age assessed with the Leiter International Performance Scale – Revised (Leiter-R; Roid & Miller, 1997) and
maternal education were included in the model as covariates. A planned follow-up HLM compared groups on the
Pragmatic Judgment subtest additionally controlling for scores on the Antonyms and Syntax Construction subtests
to ensure that differences in pragmatic ability were not due to base-line language ability (Tager-Flusberg, 2004).
Results indicated that TD boys scored higher (showed more skill) than all other groups on all three subtests and
showed more change over time, boys with FXS-O and FXS-ASD scored higher than boys with DS in syntax, and boys
with FXS-O scored higher than boys with FXS-ASD in pragmatic language (p values < .05). Within-group patterns
varied between groups.
Conclusions. Findings suggest that language production and growth across the domains of vocabulary, syntax, and
pragmatics are more impaired in boys with FXS than would be expected based on nonverbal mental age, and that
autism status affects pragmatic language in boys with FXS. Implications for assessment and intervention will be
discussed.
Funding Source. Supported by the NICHD, March of Dimes, National Fragile X Foundation, & Ireland Family
Foundation
Learning Objectives
•
To further understand language impairment as a core feature of the FXS phenotype
•
To learn about the results of this study, which suggest that autism status affects pragmatic language in
boys with FXS
Dr. Marsha Mailick Seltzer; University of Wisconsin-Madison
Title: Prevalence of CGG Expansions of the FMR1 Gene in a US Population-Based Sample
Objectives. The primary goal of this study was to calculate the prevalence of the premutation of the FMR1 gene
and of the "gray zone" using a population-based sample of older adults in Wisconsin (n = 6747 samples screened).
Compared with past research, prevalence was relatively high (1 in 151 females and 1 in 468 males for the
premutation and 1 in 35 females and 1 in 42 males for the gray zone as defined by 45 to 54 CGG repeats).
A secondary study goal was to describe characteristics of individuals found to have the premutation (n = 30, 7
males and 23 females).
Results. We found that premutation carriers had a significantly higher rate of divorce than controls, as well as
higher rates of symptoms that might be indicative of Fragile X-associated Tremor Ataxia Syndrome (FXTAS;
numbness, dizziness/faintness) and Fragile X Primary Ovarian Insufficiency (FXPOI; age at last menstrual period).
Although not statistically significant, premutation carriers were twice as likely to have a child with a disability.
Dr. Marsha Mailick Seltzer; University of Wisconsin-Madison
Title: The Family Context of FXS in Adolescence and Adulthood
Objective. The purpose of this presentation is to provide research results on the family context of FXS in
adolescence and adulthood. Our research is focused on the mutual influences of parents and their adolescent and
adult children with FXS, both how the family may affect the behavioral functioning of the son or daughter with FXS
and how the behavior of the son or daughter may affect the parents.
Results. We will first examine the association between the family environment and the behavioral functioning of
individuals with FXS across the life course. This study adds to a growing body of evidence showing that warmth and
positivity in parenting, and the absence of criticism, are associated with lower levels of behavior problems in sons
and daughters with disabilities. In individuals with FXS, we found that these associations were strongest during
childhood and adulthood, but less evident during adolescence. We then will present our findings regarding how
premutation carrier mothers of adolescents and adults with FXS are affected by the behavior problems of their
sons and daughters, and also how they are sensitive to life stress more generally.
Our findings show that maternal response is a function both of the mother’s own genetic vulnerability and her
level of stress exposure.
Conclusion. Since each family member contributes to the well-being of the entire family, consideration of the
stress and resilience of multiple family members is warranted.
Jessica Klusek, MS; University of North Carolina at Chapel Hill; [email protected]
Title: Agreement of Clinical and Research Diagnosis Among Boys And Girls With Fragile X Syndrome
Presentation Description (family friendly track)
Most children with fragile X syndrome show symptoms that are consistent with autism, such as poor eye contact
or repetitive behaviors. Prior research shows that 25-52% of males with fragile X syndrome meet diagnostic
thresholds for autism within a research setting, and 60-75% meet criteria for autism spectrum disorders. However,
relatively little is known about diagnoses received in a clinical setting. This information is important because a
child’s diagnosis is likely to influence the type and amount of services that s/he receives. Given that children with
fragile X syndrome who meet criteria for autism show different behavioral profiles than children with fragile X
syndrome without autism, and generally have poorer social and adaptive skills, knowledge of autism diagnostic
trends may inform diagnostic and intervention services for children with fragile X syndrome. This study examined
whether boys and girls with fragile X syndrome met criteria for autism in a research setting, and then compared
these data with the frequency of parent-reported clinical diagnoses. Results showed that 23% of boys with fragile X
syndrome who met criteria for autism in the research setting using a gold standard assessment tool also had a
clinical diagnosis, whereas a higher proportion of the girls (86%) who met criteria for autism in the research
setting also had a prior clinical diagnosis. These findings suggest that autism in fragile X syndrome may be underdiagnosed in clinical settings, particularly among boys. Clinical implications as well as alternative explanations of
these findings will be discussed.
Abstract
Background. Fragile X syndrome (FXS) is the most common known single gene cause of autism (Cohen et al.,
2005). Estimates obtained in a research setting using gold-standard diagnostic tools indicate that 25-52% of males
with FXS meet criteria for autistic disorder (Clifford et al., 2007; Rogers et al., 2001), and 60-74% meet criteria for
autism spectrum disorders (Garcia-Nonell et al., 2008; Hagerman & Harris, 2008). However, it is unknown whether
children with FXS who meet diagnostic thresholds for autism in research settings are also identified clinically as
having comorbid autism. Given that children with FXS and comorbid autism show different behavioral profiles than
children with FXS without autism, and generally have poorer outcomes (Bailey et al., 2001; Kau et al., 2000; Rogers
et al., 2001), further understanding of autism diagnostic practices within FXS populations will be informative for
improving diagnostic and intervention services.
Objectives: This study examined the concordance between parent-reported clinical diagnoses of autism and goldstandard research diagnoses from the Autism Diagnostic Interview-Revised (ADI-R; Lord, Rutter, & Le Couteur,
1994) among school-aged boys and girls with FXS.
Methods. Participants included 27 females and 42 males with FXS (mean age 11.10, SD = 3.64), who were recruited
from a larger research protocol examining pragmatic language in FXS. The ADI-R was administered in order to
determine autism status using gold-standard methodology. Clinical diagnoses of autism spectrum disorders were
determined via parent report within the context of a family pedigree interview, in which parents were asked
whether their child (or other relatives) had received a clinical diagnosis of autism or an ASD.
Results. Twenty-two percent of the children with FXS had received a reported clinical diagnosis of autism (19% of
males and 26% of females), whereas 54% of the children met criteria for autism on the ADI-R (71% of males and
26% of females). Of the children who met diagnostic criteria for autism on the ADI-R, 65% had no prior clinical
diagnosis (77% of males and 14% of females). Eighteen percent of the total sample was positive for autism on both
the ADI-R and clinical diagnosis-- 22% of females and 17% of males.
Conclusions. The results of this study indicate that there is poor concordance between a gold-standard autism
diagnostic tool (i.e., the ADI-R) and parent-reported clinical diagnoses of autism among school-aged children with
FXS. Only 35% of the children with FXS who met criteria for autism on the ADI-R also had received a prior clinical
diagnosis, and this discrepancy was much greater among males than females (77% of males versus 14% of the
females). Therefore, comorbid autism may often be overlooked among males with FXS, raising implications for
families’ access to services and the types of services received. Finally, this study found increased rates of autism
among children with FXS as compared to rates cited in previous research literature (e.g., Clifford et al., 2007; Harris
et al., 2008; Rogers et al., 2001), which may have been due to the use of the ADI-R, which bases diagnostic
information upon the presence of behaviors during early development. Future research should incorporate other
gold-standard autism diagnostic instruments in order to glean diagnostic information from multiple sources.
Funding Source. NICHD, 2 R01 HD038819-07 (PI: Martin, G.); NIMH, 1R03MH079998-01A1 (PI: Losh, M.)
Learning Objectives
•
To understand previous research investigating the prevalence of autism among children with fragile X
syndrome.
•
To learn about the results of this study, which show the concordance between clinical and research
diagnoses of autism among school-aged boys and girls with fragile X syndrome.