The Role of FMR1 in Pragmatic Language Impairments Associated with Autism and the Broad Autism Phenotype

Background: Strong evidence for the genetic basis of autism comes from twin and family studies showing high heritability and the expression of subthreshold features among unaffected relatives that are believed to represent genetic liability for autism (i.e,. a broad autism phenotype, or BAP). Although a single “autism gene” has not yet been identified, approximately 6-15% of cases of autism can be traced back to a broader identifiable genetic condition. Fragile X syndrome (FXS) is one of the most common known causes of autism, with approximately 25-35% of individuals with FXS receiving a comorbid autism diagnosis. As all mothers of children with FXS are known carriers of the Fragile X Mental Retardation Gene (FMR1) gene in its premutation state, examination of this population allows for exploration of potential links between subtle autism symptomatology and known genetic etiology. Given that pragmatic language impairments are universally observed in autism, have been repeatedly documented in relatives of individuals with autism, and have been described as a principal feature of the BAP (Landa, Folstein & Isaac, 1991; Landa et al., 1992), such impairments are believed to constitute genetically meaningful component features related to autism. Examining pragmatic language skills in FMR1 premutation carriers (i.e., mothers of individuals with FXS), may therefore help to illuminate a possible role of FMR1 in the presentation of autism symptomatology and the broad autism phenotype.

Objectives: This study characterized pragmatic language abilities of mothers of individuals with fragile X syndrome (who are FMR1 premutation carriers) in comparison to mothers of individuals with autism (who are at increased genetic liability to autism) and controls, in order to explore overlapping, potentially genetically-linked features of the broad autism phenotype, and to investigate the potential role of FRM1 in the pragmatic language impairments associated with the BAP.

Methods: Semi-structured conversational interviews were conducted with mothers of individuals with FXS (n=10), autism (n=10), and typically developing children (n=10). Audio-visual recordings of the interviews were reviewed and the Modified-Pragmatic Rating Scale (M-PRS; Landa et al., 1992) was used to rate pragmatic language violations

Results: Mean pragmatic language impairment ratings of the FXS and autism mothers were significantly higher than those of control mothers; FXS vs. control, t=2.66, p=.028; autism vs. control t=4.64, p=.003. Mean ratings on the PRS were: 3.75 (SD=4.63) autism; 2.33 (SD=2.45) FXS; and 0.14 (SD=0.48) controls. Ratings of the FXS and autism mothers did not differ significantly (p>.29). Item analysis of M-PRS items showed tangential speech to be the most common pragmatic language error in both groups. 

Conclusions: Both mothers of children with FXS and mothers of individuals with autism presented with overlapping impairments in pragmatic language skills, relative to controls. These findings suggest that FMR1 could play a role in pragmatic language impairments described as part of the broad autism phenotype among relatives of individuals with autism.