Language development in school-age girls with fragile X syndrome.

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability, affecting approximately 1 in every 3600 males and 1 in every 4000 to 6000 females although recent estimates suggest an even higher prevalence (Crawford et al., 2001; Fernandez-Carvajal, Walichiewicz, Xiaosen, Pan, Hagerman, & Tassone, 2009; Hagerman, 2008). The syndrome is caused by the excessive lengthening of a trinucleotide (CGG) repeat in the FMR1 gene on the X chromosome (Verkerk et al., 1991), which in turn leads to a reduction or absence of the protein (FMRP) that is normally produced by that gene (Darnell, Warren, & Warren, 2004). Language and cognitive delays are virtually universal in males with FXS (Abbeduto, Brady, & Kover, 2007). Females with FXS are less affected on average and display a wider range of behavioral and neurocognitive outcomes than affected males, with some females functioning in the intellectually average range (Keysor & Mazzocco, 2002; Mazzocco, 2001). The range of language outcomes experienced by females with FXS, however, has been relatively unexplored (Abbeduto et al., 2007; Hagerman, 2002; Hatton, Wheeler, Sideris, Sullivan et al., 2009; Murphy & Abbeduto, 2003). The present study was designed to provide data on the range of language outcomes characteristic of females with FXS. Such data will be a useful foundation for further research designed to test specific hypotheses about the nature, correlates, and causes of language impairments in affected females. There is evidence that, as a group, females with FXS have impairments in language. Mazzocco and colleagues (2006) found that in comparison to girls with typical development, girls with FXS asked fewer questions, including fewer questions that logically followed from the previous utterance. In a study of adult women, Simon et al. (2001) found that females with the full mutation had difficulty in selecting appropriate humorous endings for stories that they read relative to IQ-matched women without FXS. Simon et al. concluded that the females with FXS failed the task because they were unable to follow and make connections between the elements and propositions of a discourse (i.e., establish coherence). These studies, however, were limited by their reliance on a single measure of language. Language is not a unitary ability and thus, different aspects of language can be impaired to varying degrees across and even within neurodevelopmental disorders. In Down syndrome, for example, syntax, especially expressive syntax, is more severely impaired than is vocabulary (Chapman, 2003). In contrast, syntax, although impaired, is a relative strength in individuals with Williams syndrome (Mervis, 2009). In autism, subtypes with different profiles of relative strengths and weaknesses in language have been identified (Tager-Flusberg & Joseph, 2003). Such asynchronies across language have implications for clinical assessment and intervention and provide clues as to the nature of the learning mechanisms that are impaired in these disorders (Abbeduto, Evans, & Dolan, 2001). There is a need, therefore, to examine multiple dimensions of language within the same samples of females with FXS. Preliminary data suggest that females with FXS also manifest a profile of linguistic strengths and weaknesses. In a study focused on verbal perseveration, Murphy and Abbeduto (2007) found that males with FXS produced conversational device repetitions (e.g., “that’s a wrap” and “that’s it”) significantly more often than did females with FXS, although gender differences did not emerge for other types of perseveration (e.g., repetitions at the utterance level or topic repetitions). Such findings suggest that females with FXS may display a more nuanced profile of relative strengths and weaknesses, with some aspects of language as impaired as in their male counterparts. The small sample of females in this study (n = 8), however, makes firm conclusions impossible. The present study was designed to examine multiple dimensions of language in females with FXs, using a larger sample. In the study of several neurodevelopmental disorders, it is the distinction between lexical and syntactic development that has proven to be useful in defining the linguistic phenotype (e.g., Down syndrome and Williams syndrome). Unfortunately, there have been virtually no studies focused on the lexical or syntactic capabilities of females with FXS. In a study of adolescents and young adults, Abbeduto et al. (2003) reported that females were not as delayed as males in terms of receptive vocabulary or receptive syntax. The females in the Abbeduto et al. study, however, were quite impaired in terms of nonverbal IQ (mean score of 55.5) and not representative of the full range of affectedness. Moreover, the sample of females was quite small (n = 6). In the present study, we recruited a larger sample of females who were representative of the full range of affectedness and focused on the dimensions of vocabulary and syntax. It also is not clear what factors account for within-syndrome variation in linguistic outcomes among females with FXS (Murphy & Abbeduto, 2003). Research with boys with FXS has indicated that receptive and expressive vocabulary scores and syntax are strongly related to cognitive developmental level (Abbeduto et al., 2003; Roberts et al., 2007). This relationship also has been found for speech production in males with FXS (Roberts et al., 2005). Studies of this relationship in females, however, have yielded inconsistent findings, with some studies finding no relationship (Abbeduto et al., 2003; Murphy & Abbeduto, 2007). Interpreting these findings for females is difficult, however, because different dimensions of language have been measured across multiple studies instead of within the same group, and the studies have involved small samples comprised of only females with intellectual disabilities. In the present study, we examined the relationship for both vocabulary and syntax and with a larger and more representative sample of females with FXS. The purpose of this study was to examine receptive and expressive language, with a focus on receptive vocabulary and expressive syntax, in a group of school-age females with FXS. The first goal was to outline the range of impairments in receptive vocabulary and syntax that is typical for females with FXS. The second goal was to determine whether cognitive ability predicts receptive vocabulary and expressive syntax in this population.