Background: The evaluation of treatment efficacy for individuals with fragile X syndrome (FXS) or intellectual disability (ID) more generally has been hampered by the lack of adequate outcome measures. We evaluated expressive language sampling (ELS) as a procedure for generating outcome measures for treatment research in FXS. We addressed: (a) feasibility, (b) practice effects over two administrations, (c) test-retest reliability over the repeated administrations, and (d) construct validity. We addressed these issues for the full sample as well as for subgroups defined by age, IQ, and ASD status. Methods: Participants were 106 individuals with FXS between ages 6 and 23 years who had IQs within the range of intellectual disability (IQ < 70). ELS procedures for collecting samples in conversation and narration were followed and analyzed separately. Five measures were derived from transcripts segmented into C-units (i.e., an independent clause and its modifiers): number of C-units per minute (talkativeness), number of different word roots (vocabulary), C-unit length in morphemes (syntax), percentage of C-units containing dysfluency (utterance planning), and percentage of C-units that were fully or partly unintelligible (articulatory quality). ELS procedures were administered twice at 4-week intervals for each participant. Standardized tests and informant reports were administered and provided measures for evaluating construct validity of ELS measures.

Symptoms of autism are frequent in males with fragile X syndrome (FXS), but it is not clear whether symptom profiles differ from those of nonsyndromic ASD. Using individual item scores from the Autism Diagnostic Inventory-Revised (ADI-R), we examined which current symptoms of autism differed in boys with FXS relative to same-aged boys diagnosed with nonsyndromic ASD. In addition, different subsamples of participants were matched on autism diagnostic status and severity of autism symptoms. Between-group comparisons revealed that boys with FXS showed significantly less impairment in Social Smiling than did age-, diagnostic, and severity-matched boys with nonsyndromic ASD. Severity-matched boys with FXS showed more impairment in Complex Mannerisms than did boys with nonsyndromic ASD. Behavioral differences between FXS and nonsyndromic ASD may be of theoretical importance in understanding the causes and correlates of ASD in FXS and in developing and implementing appropriate treatments.

Background Repetitive behaviours are frequently observed in individuals with intellectual disability. The present study examined the profile, inter-correlations, and predictive correlates of repetitive behaviours in males with FXS, the leading inherited cause of intellectual disability. Specific child characteristics examined as predictors included: anxiety, nonverbal cognition, and autism social-affective symptomatology. Method Participants were 39 boys with FXS (aged 6–10 years). Repetitive behaviours were measured using the Repetitive Behavior Scale – Revised (RBS-R) – a 43-item caregiver-report measure normed on individuals with intellectual disability. Results Restricted Interests and Sensory Motor behaviours were reported as most problematic for this sample of boys, whereas Self-injurious behaviours were less problematic. All subscales of the RBS-R were significantly inter-correlated. Nonverbal IQ was negatively related, whereas anxiety and social affective symptoms of ASD were positively related, to scores for Restricted Interests. Anxiety was also positively related to scores for Compulsive behaviours and Ritualistic Sameness behaviours. Conclusions This study provides a preliminary description of repetitive behaviours in males with FXS, which may form the groundwork for future research.

Autism spectrum disorder (ASD) is a common comorbid condition in people with fragile X syndrome (FXS). It has been assumed that ASD symptoms reflect the same underlying psychological and neurobiological impairments in both FXS and non-syndromic ASD, which has led to the claim that targeted pharmaceutical treatments that are efficacious for core symptoms of FXS are likely to be beneficial for non-syndromic ASD as well. In contrast, we present evidence from a variety of sources suggesting that there are important differences in ASD symptoms, behavioral and psychiatric correlates, and developmental trajectories between individuals with comorbid FXS and ASD and those with non-syndromic ASD. We also present evidence suggesting that social impairments may not distinguish individuals with FXS with and without ASD. Finally, we present data that demonstrate that the neurobiological substrates of the behavioral impairments, including those reflecting core ASD symptoms, are different in FXS and non-syndromic ASD. Together, these data suggest that there are clinically important differences between FXS and non-syndromic ASD that are masked by reliance on the categorical diagnosis of ASD. We argue for use of a symptom-based approach in future research, including studies designed to evaluate treatment efficacy.

In the present study, we examined the profile of psychiatric symptoms in boys with fragile X syndrome (FXS) using a parent report instrument. In addition, by comparing boys with FXS to boys with nonsyndromic autism spectrum disorder (ASD) utilizing multiple matching strategies, we examined between-group differences in the types of psychiatric symptoms observed and in the strength of their concurrent associations. Across all matching strategies, symptoms of manic/hyperactive behaviors and general anxiety were more frequently reported for boys with FXS than for boys with nonsyndromic ASD. Results also indicated a positive association between social avoidance and general anxiety in FXS that was stronger than that observed in nonsyndromic ASD across all matching strategies. Theoretical and treatment implications are discussed.