Defining genetically meaningful language and personality traits in relatives of individuals with fragile X syndrome and relatives of individuals with autism

Abstract

BACKGROUND Substantial phenotypic overlap exists between fragile X syndrome (FXS) and autism, suggesting that FMR1 (the gene causing FXS) poses a significant risk for autism. Cross-population comparisons of FXS and autism therefore offer a potentially valuable method for refining the range of phenotypes associated with variation in FMR1. This study adopted a broader phenotype approach, focusing on parents who are at increased genetic liability for autism or FXS. Women who were carriers of FMR1 in its premutation state were compared with mothers of individuals with autism, and controls in an attempt to determine whether subtle features of the broad autism phenotype may express at elevated rates among FMR1 premutation carriers. METHODS The principal personality and language features comprising the broad autism phenotype (i.e., rigid and aloof personality, and particular patterns of pragmatic language use) were assessed among 49 premutation carriers who were mothers of individuals with FXS, 89 mothers of individuals with autism, and 23 mothers of typically developing individuals. RESULTS Relative to controls, the autism and premutation parent groups showed elevated rates of certain personality and language characteristics which have been described as constituting the broad autism phenotype. CONCLUSIONS Findings suggest partially overlapping personality and language profiles among autism and premutation parent groups, with rigid personality style and patterns of pragmatic language use emerging as features most clearly shared between groups. These results provide further evidence for the overlap of autism and FXS, and may implicate FMR1 in some of the subtle features comprising the broad autism phenotype.

A Comparison of Pragmatic Language in Boys With Autism and Fragile X Syndrome

“…Furthermore, premutation carriers of FMR1 show subclinical pragmatic features that are similar in quality and severity with those seen in the broad autism phenotype, which supports a role of FMR1 in a broad range of pragmatic language features associated with ASD (Losh, Klusek, et al, 2012). Thus, the delineation of pragmatic language features that may overlap or diverge in ASD and FXS is a promising method for identifying phenotypic commonalities that may stem from biological disruptions associated with FMR1 .…”

“…The groups were similar in race, household income, and maternal education level ( ps > .112); see Table 2. The standardized pragmatic language data for forty-two children (5 with ASD-O, 9 with FXS-ASD, 3 with FXS-O, 7 with DS, 18 with TD) have been previously analyzed by Losh et al (2012).…”

“…A recent investigation by Losh et al (2012) highlights the importance of multimodal pragmatic language assessment. This study examined pragmatic language abilities among boys with idiopathic ASD and boys with FXS who did or did not have comorbid ASD, using a standardized measure of pragmatic language (the Pragmatic Judgment subtest of the Comprehensive Assessment of Spoken Language; CASL-PJ; Carrow-Woolfolk, 1999) and a teacher-report measure of communication skills (the Children’s Communication Checklist-2; CCC-2; Bishop, 2006).…”

Cognitive Functioning in the Broad Autism Phenotype

“…Consequently, Wilson and associates (2013) proposed that phonological processing differences in the brain appear to be a basic feature of the BAP. However, similar to Losh et al (2012), Wilson et al (2013) indicated that replication of their findings are necessary before any firm conclusions can be drawn.…”

Phenobarbital use and neurological problems in FMR1 premutation carriers

“…Individual carriers of the fragile X premutation (CGG repeats between 55 and 200) are at high risk for developing a neurodegenerative disorder called Fragile X-associated tremor/ataxia syndrome (FXTAS) (Garcia-Arocena and Hagerman, 2010). Additionally, carriers can develop neuropathy, fertility problems, executive function deficits, attention deficits, memory problems, language dysfluencies, affective disorders, anxiety, attention deficit/hyperactivity disorder (ADHD) and sleep problems (Sullivan et al, 2011; Seltzer et al, 2012; Losh et al, 2012; Hagerman and Hagerman, 2013). Approximately 20% of the female carriers develop fragile-X-associated primary ovarian insufficiency (FXPOI) (Sullivan et al, 2011).…”