Autism Spectrum Disorder in Children and Adolescents With Fragile X Syndrome: Within-Syndrome Differences and Age-Related Changes

Abstract

The Autism Diagnostic Interview-Revised was used to examine diagnostic profiles and age-related changes in autism symptoms for a group of verbal children and adolescents with FXS, with and without autism. After controlling for nonverbal IQ, statistically significant between-group differences for lifetime and current autism symptoms were found for the Communication and Restricted Interests/Repetitive Behaviors domains, but not the Reciprocal Social Interaction domain. Effect sizes for differences in Reciprocal Social Interaction also were smaller than effect sizes for the other domains with one exception. Overall, severity of autism symptoms improved with age for all participants, with the least improvement noted for Restricted Interests and Repetitive Behaviors. FMRP did not account for unique variance in autism symptoms over and above nonverbal IQ. KeywordsFragile X syndrome; autism; diagnosis; intellectual disability; behavioral phenotype Autism Spectrum Disorder in Children and Adolescents with Fragile X Syndrome: Within-Syndrome Differences and Age-Related ChangesFragile X syndrome (FXS) is the most common inherited cause of intellectual disability. In general, prevalence rates have been reported as 1 in 4000 males and 1 in 8000 females (Crawford et al., 2001); however, recent studies have yielded rates closer to 1 in 2500 (Fernandez-Carvajal., Walichiewicz, Xiaosen, Pan, Hagerman, & Tassone, 2009;Hagerman, 2008). FXS is caused by an expansion of a repetitive CGG nucleotide sequence in the FMR1 gene, located on the X chromosome (Kaufmann & Reiss, 1999). This expansion causes methylation and transcriptional silencing of the gene, resulting in a reduction or absence of the protein that is normally produced (Kaufmann, Cortell, Kau, et al., 2004). This protein (FMRP) is critical for the regulation of processes involved in synaptic maturation, axonal guidance, and experience-dependent learning (Darnell, Warren, & Darnell, 2004;Hagerman, Ono, & Hagerman, 2005). Behaviors characteristic of autism are frequent in FXS, with many individuals meeting diagnostic criteria for autism (Hagerman, 1999 NIH Public Access Author ManuscriptAm J Intellect Dev Disabil. Author manuscript; available in PMC 2011 January 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript prevalence of autism in FXS at 25%, although recent studies utilizing diagnostic criteria for the full spectrum of autism disorders (i.e., inclusive of PDD-NOS) have reported rates approaching 50% (Demark, Feldman, & Holden, 2003;Kaufmann et al, 2004;Philofsky, Hepburn, Hayes, Hagerman, & Rogers, 2004). In the present study, we were interested in within-syndrome differences in, and the age-related trajectories of, autism symptoms in FXS.Although the association between FXS and autism has been well documented, the developmental course of autism within FXS is not well understood. It is not known whether the symptoms of autism are stable across development in FXS or whether there is an abatement of symptoms with age as has been observ...

Noncomprehension Signaling in Males and Females With Fragile X Syndrome

“…Previous studies have demonstrated significant associations between autism symptom severity, nonverbal cognitive ability, and FMRP in individuals with FXS. However, the correlations between FMRP and autism symptom severity often do not remain after controlling for differences in nonverbal IQ (e.g., Hatton et al, 2006;Kover et al, 2013;McDuffie et al, 2010;Thurman, McDuffie, Kover, Hagerman, & Abbeduto, 2015). Thus, given that our models of noncomprehension ability included both FMRP and nonverbal cognitive ability and the fact that nonverbal IQ seems to play a role in the presence of ASD symptomatology in FXS, it may not be surprising that autism symptomatology failed to emerge as a significant predictor.…”

“…All participants were drawn from a larger project focused on the language and communicative development of children and adolescents with FXS or Down syndrome relative to younger TD children. Findings in this project have been reported in several publications Kover, Pierpont, Kim, Brown, & Abbeduto, 2013;McDuffie et al, 2010;McDuffie, Kover, Abbeduto, Lewis, & Brown, 2012;Oakes, Kover, & Abbeduto, 2013;Pierpont, Richmond, Abbeduto, Kover, & Brown, 2011), but none have focused on measures of noncomprehension signaling. Families were recruited by advertisements in local newspapers, mailings to local educators and administrators of genetic clinics, notices to families enrolled in a university research registry, postings on Internet website and listservs, and announcements in the newsletters of national organizations focused on developmental disabilities.…”

Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics

“…expressive language abilities compared with individuals having FXS alone (45). Most individuals with FXS and ASD have, in addition to the described hand mannerisms and speech problems, significant deficits in social interaction and communication persistently over time (46).…”

Growth of Expressive Syntax in Children With Fragile X Syndrome

“…The prevalence of autism in FXS is estimated between 25% and 50% (see McDuffie et al, 2010), and is often an indicator of greater delays in communication and language (Abbeduto et al, 2007;Lewis et al, 2006;Philofsky, Hepburn, Hayes, Hagerman, & Rogers, 2004;Roberts, Mirrett, & Burchinal, 2001;Warren, Brady, Sterling, Fleming, & Marquis, 2010). However, several studies have reported no distinct language profiles between individuals with comorbid FXS and autism and individuals with FXS only, particularly in areas of expressive language, such as morphosyntax (Estigarribia et al, 2011;Lewis et al, 2006;Price et al, 2008), lexical diversity, talkativeness, and dysfluency .…”