Autism Spectrum Disorder in Fragile X Syndrome: A Longitudinal Evaluation

Kennedy Krieger Institute, Baltimore, MD 21211, USA.
American Journal of Medical Genetics Part A (Impact Factor: 2.16). 06/2009; 149A(6):1125-37. DOI: 10.1002/ajmg.a.32848
Source: PubMed


The present study extends our previous work on characterizing the autistic behavior profile of boys with fragile X syndrome (FXS) who meet Diagnostic and Statistical Manual for Mental Disorders, 4th Edition criteria for autism spectrum disorder (ASD) into a longitudinal evaluation of ASD in FXS (FXS + ASD). Specifically, we aimed to determine the stability of the diagnosis and profile of ASD in FXS over time. Through regression models, we also evaluated which autistic and social behaviors and skills were correlates of diagnosis and autistic behavior severity (i.e., Autism Diagnostic Interview-Revised total scores). Finally, we assessed the evolution of cognitive parameters in FXS + ASD. A population of 56 boys (30-88 months at baseline) with FXS was evaluated using measures of autistic, social, and cognitive behaviors and skills at three yearly evaluations. We found that the diagnosis of ASD in FXS was relatively stable over time. Further emphasizing this stability, we found a set of behaviors and skills, particularly those related to peer relationships and adaptive socialization, that differentiated FXS + ASD from the rest of the FXS cohort (FXS + None) and contributed to autistic severity at all time points. Nevertheless, the general improvement in autistic behavior observed in FXS + ASD coupled with the concurrent worsening in FXS + None resulted in less differentiation between the groups over time. Surprisingly, FXS + ASD IQ scores were stable while FXS + None non-verbal IQ scores declined. Our findings indicate that ASD is a distinctive subphenotype in FXS characterized by deficits in complex social interaction, with similarities to ASD in the general population.

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Available from: Richard E Thompson, Jun 03, 2014
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    • "Furthermore, there was a significant decrease on the repetitive behavior and social interaction domains between T1 and T2. Stability of diagnostic classifications of ASD in FXS has been reported in previous studies (Hatton et al., 2006; Hernandez et al., 2009; Sabaratnam et al., 2003). "
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    • "Research has investigated the impact of comorbid ASD in FRAX by comparing individuals with comorbid ASD to those with FRAX only. Such research has reported lower IQ (Hagerman et al., 1986), greater deficits in adaptive functioning (Turk & Graham, 1997), and greater deficits in socialization (Hernandez et al., 2009) in those with comorbid ASD when compared to those with FRAX only. This research suggests that presence of comorbid ASD in FRAX may result in a poorer prognosis. "
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    • "Different combinations of these three disorders have also occurred together in patients. Numerous studies have reported a range of percentages for the prevalence of such overlapping patient groups, and are shown in Figure 2. The co-diagnosis rate of an ASD disorder in male Fragile X patients ranges from 25 to 46% (Muhle et al., 2004; Abrahams and Geschwind, 2008; Bailey et al., 2008; Hernandez et al., 2009). The corresponding rate for epilepsy in male Fragile X patients is lower, ranging from 10 to 18% (Musumeci et al., 1999; Muhle et al., 2004; Bailey et al., 2008), whereas the occurrence of epilepsy in ASD patients varies more widely from 6.6 to 37% (Amiet et al., 2008; Yasuhara, 2010; Jokiranta et al., 2014). "
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