Autism spectrum disorder in fragile X syndrome: Communication, social interaction, and specific behaviors

Abstract

The present study extends our previous work on social behavior impairment in young males with fragile X syndrome (FraX). Specifically, we evaluated whether the autistic phenomenon in FraX is expressed as a range of behavioral impairments as in idiopathic autism (Aut). We also examined whether there are behaviors, identified as items of the Autism Diagnostic Interview-Revised (ADI-R), that in FraX predispose to or differentiate subjects with autism spectrum disorder (ASD) diagnosis. Finally, regression models were utilized to test the relative contribution of reduced communication and socialization skills to ADI-R scores and diagnoses. A cohort of 56 boys (3-8 years) with FraX was examined in terms of scores on measures of cognition (IQ was a co-variate in most analyses.), autistic behavior, problem/aberrant behavior, adaptive behavior, and language development. We found that, indeed, in terms of problem behavior and adaptive skills, there is a range of severity from FraX + Aut to FraX + PDD (Pervasive Developmental Disorder) to FraX + none. ADI-R items representing "Play" types of interaction appear to be "susceptibility" factors since they were abnormal across the FraX cohort. Integrated regression models demonstrated that items reflecting complex social interaction differentiated the FraX + ASD (Aut + PDD) subgroup from the rest of the FraX cohort, while abnormalities in basic verbal and non-verbal communication distinguished the most severely affected boys with FraX + Aut from the milder FraX + PDD cohort. Models incorporating language, adaptive communication, and adaptive socialization skills revealed that socialization was not only the main influence on scores but also a predictor of ASD diagnosis. Altogether, our findings demonstrate that the diagnosis of ASD in FraX reflects, to a large extent, an impairment in social interaction that is expressed with variable severity in young males with FraX.

Sex Chromosome Complement and Gonadal Sex Influence Aggressive and Parental Behaviors in Mice

“…Within human populations, mutations of X-linked genes affect mental capacity; in the extreme form are conditions like fragile-X, and milder cases may involve autism (Petit et al, 1996;Thomas et al, 1999;Jamain et al, 2003;Kaufmann et al, 2004). In humans, sex differences in both parental nurturing behavior and aggression are widely acknowledged, as well as individual variation in same-sex populations.…”

Abnormal Mechanisms of Plasticity and Metaplasticity in Autism Spectrum Disorders and Fragile X Syndrome

“…FXS is the most common genetic cause of autism, with 30% of children with FXS diagnosed with autism and 2%-5% of autistic children having FXS (Kaufmann et al 2004). Evidence both from animal FXS models (Simonyi et al 2005) (Huber et al 2002) and from studies in patients with FXS conducted in our laboratory indicate that loss of Fragile X mental retardation protein FMRP (the physiological consequence of the genetic mutation that leads to FXS) leads to abnormalities in synaptic plasticity.…”

Identification of Expanded Alleles of theFMR1Gene Among High-Risk Population in Indonesia by Using Blood Spot Screening

“…Although prevalence estimates vary across studies, there is agreement that the risk of autism spectrum disorders (ASD) is higher in FXS than in many other neuro-developmental disorders. From recent studies, *2% to 6% of children with ASD have FXS (Li et al, 1993;Wassink et al, 2001;Estecio et al, 2002;Hagerman, 2002;Reddy, 2005), and *30% of children with FXS have ASD (see Appendix in Rogers et al, 2001;Kaufmann et al, 2004); Pervasive Developmental Disorder-Not Otherwise Specified is seen in an additional 30% (Harris et al, 2008). In fact, FXS is characterized by a broad spectrum of behavioral and emotional impairment, psychological problems, and learning disabilities in those without mental retardation or ID.…”