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Autism in Fragile X Syndrome: A Category Mistake?

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Objective

Many investigators now routinely classify children with fragile X syndrome (FXS) according to whether or not they also meet diagnostic criteria for autism. To determine whether this classification is appropriate, we examined the profiles of autistic behaviors shown by boys and girls with FXS.

Method

Individuals with FXS, aged 5 to 25 years, were assessed on two established measures of autism, the Social Communication Questionnaire (SCQ) and the Autism Diagnostic Observation Schedule (ADOS).

Results

We found that 35.1% of boys and 4.3% of girls with FXS scored in the “autism” category on both instruments. Analysis of the symptom profile indicated that both boys and girls with FXS showed lower rates of impairment on communication and reciprocal social interaction items than the reference autism samples on the measures. Furthermore, a regression model showed that IQ was significantly negatively associated with the SCQ total score in both boys and girls with FXS, when controlling for age, medication use, and FMRP levels.

Conclusions

These data suggest that there are significant differences in the profile of social and communicative symptomatology in FXS compared with individuals diagnosed with idiopathic autism. Given these differences, the implementation of standard autism interventions for individuals with FXS may not be optimal. Maintaining the conceptual distinction between FXS (an established biological disease) and idiopathic autism (a phenomenologically defined behavioral disorder) may also facilitate the development of more targeted and thus effective interventions for individuals with FXS in the future.

Section snippets

Subjects

Participants were 120 children, adolescents, and young adults (47 girls and 73 boys) aged 5 to 25 years. The mean ages of the boys and girls were 13.24 (SD = 3.27) years and 13.47 (SD = 4.6) years, respectively. A total of 60 (50%) participants had taken part in a previous study investigating the association between autistic, self-injurious, and compulsive behaviors in FXS.42 Participants had been diagnosed with the full mutation associated with FXS (>200 CGG repeats and evidence of aberrant

Results

As expected with an X-linked genetic disorder, IQ scores were significantly higher in girls with FXS (mean = 76.77, SD = 22.76, range = 40–116) than in boys with FXS (mean = 45.66, SD = 7.94, range = 40–74) [t(118) = 10.78, p < 0.001] and FMRP values were significantly higher in girls (mean = 53.02, SD = 18.59, range = 14.5–90) than in boys (mean = 13.91, SD = 14.42, range = 1.5–74) [t(118) = 12.67, p < 0.001]. Total scores on the SCQ were significantly higher in boys (mean = 17.14, SD = 6.74,

Discussion

The first aim of this study was to examine the prevalence of autistic behaviors in individuals with FXS. To accomplish this objective, we administered two well-known measures of autistic behaviors to a large sample of individuals with FXS. Both of these instruments are widely used in the autism literature; the SCQ is a checklist that parallels ADI-R content, whereas the ADOS is an observational measure of autistic behaviors that is often considered the “gold-standard” in autism research.

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    This research was supported by National Institute of Mental Health grants MH50047 and MH01142 and the Canel Fragile X Family Fund.

    Disclosure: Drs. Hall, Lightbody, and Reiss, and Ms. Hirt and Ms. Rezvani report no biomedical financial interests or potential conflicts of interest.

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