Jessica Klusek

Language Characteristics of Individuals with Down Syndrome

On average, language and communication characteristics of individuals with Down syndrome (the most common genetic cause of intellectual disability) follow a consistent profile. Despite considerable individual variability, receptive language is typically stronger than expressive language, with particular challenges in phonology and syntax. We review the literature on language and literacy skills of individuals with Down syndrome, with emphasis on the areas of phonology, vocabulary, syntax, and pragmatics. We begin by describing the hearing, oral-motor, cognitive, social, and prelinguistic and early nonverbal communication characteristics of individuals with Down syndrome. We conclude with a discussion of clinical implications and research directions.

Social communication and theory of mind in boys with autism and fragile x syndrome.

Impairments in the social use of language, or pragmatics, constitute a core characteristic of autism. Problems with pragmatic language have also been documented in fragile X syndrome (FXS), a monogenic condition that is the most common known genetic cause of autism. Evidence suggests that social cognitive ability, or theory of mind, may also be impaired in both conditions, and in autism, may importantly relate to pragmatic language ability. Given the substantial overlap observed in autism and FXS, this study aimed to better define those social-communicative phenotypes that overlap in these two conditions by comparing pragmatic language ability and theory of mind in children with idiopathic autism and children with FXS, with and without autism, as well as children with Down syndrome and typically developing controls. We further examined correlations between these cognitive-behavioral phenotypes and molecular genetic variation related to the Fragile X Mental Retardation-1 gene (FMR1) in the FXS group. Results indicated that children with idiopathic autism and those with FXS and autism performed comparably on direct-assessment measures of pragmatic language and theory of mind, whereas those with FXS only did not differ from controls. Theory of mind was related to pragmatic language ability in all groups. Pragmatic language and theory of mind also correlated with genetic variation at the FMR1 locus (Cytosine-Guanine-Guanine repeats and percent methylation). These results point toward substantial overlap in the social and language phenotypes in autism and FXS and suggest a molecular genetic basis to these phenotypic profiles.

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

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. 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. Relative to controls, the autism and premutation parent groups showed elevated rates of certain personality and language characteristics of the broad autism phenotype. 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.

Consistency between Research and Clinical Diagnoses of Autism among Boys and Girls with Fragile X Syndrome.

BACKGROUND Prior research suggests that 60-74% of males and 16-45% of females with fragile X syndrome (FXS) meet criteria for autism spectrum disorder (ASD) in research settings. However, relatively little is known about the rates of clinical diagnoses in FXS and whether such diagnoses are consistent with those performed in a research setting using gold standard diagnostic tools. METHOD This study explored whether boys and girls with FXS met criteria for ASD in a research setting using the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R), and then compared these data with the frequency of parent-reported clinical diagnoses. We also examined child and family characteristics as potential diagnostic predictors across settings. Participants included 35 females and 51 males with FXS (mean age: 10 years), who were from Eastern and Midwestern regions of the USA. RESULTS About half of the children met criteria for ASD on either the ADOS or ADI-R, with ASD occurring three times more frequently in males than females (∼75% vs. ∼25%). In contrast, ∼25% of participants of both genders had received a clinical diagnosis of ASD. While cognitive and language skills predicted diagnostic outcome on the ADOS and ADI-R, these skills did not predict clinical diagnoses. Executive functions predicted clinical diagnoses, but not diagnoses per the ADOS or ADI-R. CONCLUSIONS ASD in FXS may be under-diagnosed in clinical/educational settings, which raises questions regarding access to ASD-related services.

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

PURPOSE Impaired pragmatic language (i.e., language use for social interaction) is a hallmark feature of both autism spectrum disorder (ASD) and fragile X syndrome (FXS), the most common known monogenic disorder associated with ASD. However, few cross-population comparisons of ASD and FXS have been conducted, and it is unclear whether pragmatic language profiles in these conditions overlap. METHOD The authors used seminaturalistic and standardized assessment methods to characterize pragmatic language abilities of 29 school-aged boys with idiopathic ASD, 38 with FXS and comorbid ASD, 16 with FXS without ASD, 20 with Down syndrome, and 20 with typical development. RESULTS Similar severity of pragmatic language deficits was observed in both of the groups with ASD (idiopathic and fragile X-associated). ASD comorbidity had a detrimental effect on the pragmatic language skills of the boys with FXS. Some different patterns emerged across the two pragmatic assessment tools, with more robust group differences observed in pragmatics assessed in a seminaturalistic conversational context. CONCLUSION These findings have implications for pragmatic language assessment and intervention, as well as for understanding the potential role of the fragile X gene, Fragile X Mental Retardation-1, in the pragmatic language phenotype of ASD.

Cardiac autonomic regulation in autism and Fragile X syndrome: a review.

Despite the significance of efforts to understand the biological basis of autism, progress in this area has been hindered, in part, by the considerable heterogeneity in the disorder. Fragile X syndrome (FXS), a monogenic condition associated with high risk for autism, may pave the way for the dissection of biological heterogeneity within idiopathic autism. This article adopts a cross-syndrome biomarker approach to evaluate potentially overlapping profiles of cardiac arousal dysregulation (and broader autonomic dysfunction) in autism and FXS. Approaches such as this, aimed at delineating shared mechanisms across genetic syndromes, hold great potential for improving diagnostic precision, promoting earlier identification, and uncovering key systems that can be targeted in pharmaceutical/behavioral interventions. Biomarker approaches may be vital to deconstructing complex psychiatric disorders and are currently promoted as such by major research initiatives such as the NIMH Research Domain Criteria (RDoC). Evidence reviewed here supports physiological dysregulation in a subset of individuals with autism, as evidenced by patterns of hyperarousal and dampened parasympathetic vagal tone that overlap with the well-documented physiological profile of FXS. Moreover, there is growing support for a link between aberrant cardiac activity and core deficits associated with autism, such as communication and social impairment. The delineation of physiological mechanisms common to autism and FXS could lend insight into relationships between genetic etiology and behavioral endstates, highlighting FMR1 as a potential candidate gene. Research gaps and potential pitfalls are discussed to inform timely, well-controlled biomarker research that will ultimately promote better diagnosis and treatment of autism and associated conditions.

Physiological Arousal in Autism and Fragile X Syndrome: Group Comparisons and Links With Pragmatic Language

This study tested the hypothesis that pragmatic (i.e., social) language impairment is linked to arousal dysregulation in autism spectrum disorder (ASD) and fragile X syndrome (FXS). Forty boys with ASD, 39 with FXS, and 27 with typical development (TD), aged 4-15 years, participated. Boys with FXS were hyperaroused compared to boys with TD but did not differ from boys with ASD. Dampened vagal tone predicted pragmatic impairment in ASD, and associations emerged between cardiac activity and receptive/expressive vocabulary across groups. Findings support autonomic dysfunction as a mechanism underlying pragmatic impairment in ASD and suggest that biophysiological profiles are shared in ASD and FXS, which has implications for understanding the role of fragile X mental retardation-1 (FMR1, the FXS gene) in the pathophysiology of ASD.

Sex differences and within-family associations in the broad autism phenotype:

While there is a strong sex bias in the presentation of autism, it is unknown whether this bias is also present in subclinical manifestations of autism among relatives, or the broad autism phenotype. This study examined this question and investigated patterns of co-occurrence of broad autism phenotype traits within families of individuals with autism. Pragmatic language and personality features of the broad autism phenotype were studied in 42 fathers and 50 mothers of individuals with autism using direct assessment tools used in prior family studies of the broad autism phenotype. Higher rates of aloof personality style were detected among fathers, while no sex differences were detected for other broad autism phenotype traits. Within individuals, pragmatic language features were associated with the social personality styles of the broad autism phenotype in mothers but not in fathers. A number of broad autism phenotype features were correlated within spousal pairs. Finally, the associations were detected between paternal broad autism phenotype characteristics and the severity of children’s autism symptoms in all three domains (social, communication, and repetitive behaviors). Mother–child correlations were detected for aspects of communication only. Together, the findings suggest that most features of the broad autism phenotype express comparably in males and females and raise some specific questions about how such features might inform studies of the genetic basis of autism.

Pragmatic Language Features of Mothers With the FMR1 Premutation Are Associated With the Language Outcomes of Adolescents and Young Adults With Fragile X Syndrome

PURPOSE Pragmatic language difficulties have been documented as part of the FMR1 premutation phenotype, yet the interplay between these features in mothers and the language outcomes of their children with fragile X syndrome is unknown. This study aimed to determine whether pragmatic language difficulties in mothers with the FMR1 premutation are related to the language development of their children. METHOD Twenty-seven mothers with the FMR1 premutation and their adolescent/young adult sons with fragile X syndrome participated. Maternal pragmatic language violations were rated from conversational samples using the Pragmatic Rating Scale (Landa et al., 1992). Children completed standardized assessments of vocabulary, syntax, and reading. RESULTS Maternal pragmatic language difficulties were significantly associated with poorer child receptive vocabulary and expressive syntax skills, with medium effect sizes. CONCLUSIONS This work contributes to knowledge of the FMR1 premutation phenotype and its consequences at the family level, with the goal of identifying modifiable aspects of the childs language-learning environment that may promote the selection of treatments targeting the specific needs of families affected by fragile X. Findings contribute to our understanding of the multifaceted environment in which children with fragile X syndrome learn language and highlight the importance of family-centered intervention practices for this group.

Phonological Awareness and Reading in Boys with Fragile X Syndrome.

BACKGROUND Reading delays are well documented in children with fragile X syndrome (FXS), but few studies have examined linguistic precursors of reading in this population. This study examined the longitudinal development of phonological awareness and its relationship with basic reading in boys with FXS. Individual differences in genetic, social-behavioral and environmental factors were also investigated as predictors of phonological awareness. METHODS Participants included 54 boys with FXS and 53 typically developing (TD) mental age-matched peers who completed assessments of phonological awareness, nonverbal intelligence, and reading annually for up to 4 years. FMRP level and autism symptomatology were also measured within the FXS group. Hierarchical linear modeling was used to examine change in phonological awareness over time and its predictors. Linear regression was used to examine phonological awareness as a predictor of word reading. RESULTS Boys with FXS exhibited slower growth than TD peers in phonological awareness only when nonverbal cognitive abilities were not controlled. The rate of change in phonological awareness decreased significantly after age 10 in boys with FXS. Phonological awareness accounted for 18% unique variance in basic reading ability after controlling for nonverbal cognition, with similar relationships across groups. CONCLUSION Phonological awareness skills in the boys with FXS were commensurate with their nonverbal cognitive abilities, with similar relationships between phonological awareness and reading as observed in the TD mental age-matched peers. More research is needed to examine potential causal relationships between phonological awareness, other language skills, and reading abilities in individuals with FXS and other neurodevelopmental disorders.