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  • Fragile X

Gesture Development in Infants with Fragile X Syndrome

Killian R. Hughes, B.A.

Jessica Klusek, Ph.D., CCC-SLP., Carsyn Butler, B.A., & Jane E. Roberts, Ph.D.


Fragile X syndrome (FXS) is the most common known cause of inherited intellectual disability and also the most common known genetic cause of autism spectrum disorder (ASD; Flenthrope & Brady, 2010). About 60% of males diagnosed with FXS meet criteria for ASD (Klusek et al., 2014). Communication impairments are well documented in FXS and ASD; however, limited research has been done to examine early communication in FXS. Gesture use is one of the earliest signs of intentionality and can serve as an early red flag for atypical communication development, even before delays in spoken language are evident (Crais et al, 2009). This study presents a cross-sectional analysis of gesture use in infants with TD, FXS, and siblings of individuals with ASD (ASIBS) at 12 months of age. Our goals were to examine the frequency and function (i.e. behavioral regulation, social interaction, and joint attention) of gesture use in infants at 12-months of age to determine if between-group differences in gestures use are helpful for early detection of language delays. Gestures were coded from the Autism Observation Scale for Infants (AOSI; Bryson et el., 2007), using the schema outlined by Watson et al. (2013), which included a checklist of communicative gestures and their functions. Results from a series of statistical analyses indicated a significantly lower frequency of gesture use in infants with FXS compared to infants with TD and similar rates of gesture use among infants with FXS and ASIBS.



Fragile X syndrome (FXS) is a genetically based neurodevelopmental condition, which occurs in approximately 1 in 4,000 in males and 1 in 6,000 in females (Sherman et al., 2005; Turner et al., 1996). FXS is the most common inherited cause of intellectual disability and is caused by a mutation in the Fragile X Mental Retardation 1 (FMR1) gene located on the X chromosome. There is an increased number of CGG trinucleotide repeats on the FMR1 gene with this expansion attributed for the dysfunction (Verkerk et al., 1991). Individuals with FXS have over 200 CGG repeats in the FMR1 gene, while those who have between 55-200 CGG are considered to be premutation carriers of FXS. Females with FXS tend to be less affected because typically the full mutation is only found on one of their two X chromosomes, allowing for the unaffected X chromosome to compromise the effects. The mutation inhibits the production of Fragile X Mental Retardation Protein that is essential for brain development. Typical results of the FXS phenotype include several physical, cognitive and behavioral delays. Physical features of FXS may not be obvious in young children, so other cognitive and behavioral features are more heavily relied on for diagnosis (Abbeduto, 1997). In addition to being the most common known genetic cause of autism spectrum disorder (ASD), FXS is also characterized by intellectual impairment, limited attention span, hyperactivity, social withdrawal and communication impairments (Roberts et al., 2005; Cohen et al., 2005).

About 60% of males diagnosed with FXS meet criteria for ASD, a pervasive developmental disorder (Klusek et al., 2014). Unlike FXS, which is diagnosed through genetic testing, ASD is defined behaviorally. Typically, ASD is defined by impairments in social and communication development, features also commonly associated with FXS (American Psychiatric Association, 2013). Understanding the overlap in ASD and FXS may offer insight for a potential relationship between the FMR1 gene and features of ASD. A comorbid diagnosis of FXS and ASD increases the deficits in social-communicative abilities and is central to FXS profiles (Marschik et al., 2014).

ASD occurs in 1 in 42 males and 1 in 189 females (Baio, 2014). Diagnostic criteria for ASD include persistent deficits in social communication and social interaction across multiple contexts, and restricted, repetitive patterns of behavior, interests, or activities (American Psychiatric Association, 2013). The etiology of ASD is still unclear, however, a large body of research suggests a familial-genetic influence. Younger siblings of individuals diagnosed with ASD (ASIBS) are at a high-risk of developing ASD, with a recurrence rate of about 20% (Ozonoff et al., 2011). Therefore, studying ASIBS allows for a greater understanding of the genetic implications related to ASD. In addition to an increased risk of developing ASD, Yirmiya et al. (2006) found nearly 20 percent of ASIBS displayed deficits similar to those defining ASD, including communication abnormalities. Efforts to improve early identification of ASD have been limited due to concerns about the limitations of available screening tools; however, a promising area of study is gesture use in children (Watson et al., 2013).

Research on particular communication domains suggests a specific communication profile of FXS. Although there is considerable variation in skills, the communication profile is a feature that regularly prompts the possibility of a FXS diagnosis (Roberts et al., 2005; Abbeduto, 1997). Communication impairments are to be expected due to the cognitive and social delays in associated with FXS and include both verbal and nonverbal deficits such as difficulties with speech production, pragmatic skills, eye gaze avoidance, social withdrawal, atypical play and imitation behaviors. Communication impairments are well documented in adolescents and adults with FXS, however, little is known about the early development of communication deficits in FXS. Gesture use is one of the earliest signs of intentionality and can serve as an early red flag for atypical communication development, even before delays in spoken language are evident (Crais et al., 2009).

Gesture Development

Early gesture use in typically developing children (TD) is seen between 7 and 9 months of age (Crais, Douglas, & Campbell, 2004; Guidetti & Nicoladis, 2008; Iverson & Goldin-Meadow, 2005). By 12 months of age, varied forms of gestures emerge and serve a range of communicative functions that are closely related to vocabulary development (Watson et al., 2013; Rowe et al., 2008). The communicative functions of gestures can be broken down into Bruner’s (1981) three earliest functions of intentional communication: behavioral regulation (BR), social interaction (SI) and joint attention (JA). Behavior regulation gestures are the first to emerge around the age of 6 months, often in the form of protesting, and are used to regulate another person’s behavior (Watson et al., 2013; Crais et al., 2004). The next to typically emerge are gestures used for social interaction followed by joint attention gestures. SI gestures emerge around the age of 9 months, are used to attract a person’s attention to engage in social interaction such as initiating or sustaining a social game or routine. JA gestures are typically the last to emerge between the ages of 9 and 12 months. JA gestures are used to direct another person’s attention to an object or event, for example, pointing to an object to show shared interest. These functions represent a continuum of sociability with BR placed on the low end and JA placed on the high end, revealing that significant differences in their use should be considered for early identification of language delays (Flenthrope & Brady, 2010). Despite the importance of this topic, very little is known about early gesture use in infants with FXS.


Gestures in children with ASD

By the end of the first year of life, children with ASD display deficits in gesture use compared to TD infants. Infants with ASD show a reduced frequency of gesture use as early as nine months of age (Watson et al., 2013). Children with ASD also differ in the functions of their gesture use. Wetherby (1993) found children with ASD display a predominance of BR gestures and are deficient in their use of gestures to engage in social interaction or joint attention functions. However, children with ASD display less difficulty in the use of SI gestures compared to JA gestures despite common social deficits central to ASD profiles (McEvoy, Rogers, & Pennington, 1993). Mitchel et al. (2006) found that ASIBS who were later diagnosed with ASD produced fewer gestures than infants with TD at 12 months of age. ASIBS later diagnosed with ASD also displayed significantly fewer gestures for the use of BR and JA functions compared to infants with TD and ASIBS who were not later diagnosed with ASD (Rozga et al., 2011).

Gestures in children with FXS

In a small study of 11 nine-month old male infants with FXS, overall developmental delays were detected at nine months of age by several screening measures as part of a comprehensive developmental assessment (Mirrett et al., 2004). Marschik et al. (2014) reported infants with FXS displayed a limited range of early communication skills, such as facial expressions and pre-linguistic communication (i.e., babbling), compared to typically developing infants. Additionally, gesture use was only identified in one of out 7 infants with FXS (Marschik et al., 2014). Kover et al. (2014) provided evidence of visual attention as a predictor of language delays in infants with FXS at 12 months of age and were able to identify delays in language abilities in infants with FXS compared to infants with TD at 12 months of age. However, existing literature has not examined early gesture development in infants with FXS at 12 months of age. Studies of later development of FXS yield more information on gesture use in children with FXS. Roberts et al. (2002) collected data on toddlers and preschoolers between the ages of 20-86 months with FXS using the Communication and Symbolic Behavior Scales (CSBS; Wetherby & Prizant, 2002) and found an overall weakness in communication skills and a relative weakness in gesturing. Despite providing evidence of delayed language ability, the large gap in age limits conclusions about the early development of communication in FXS (Kover et al., 2014). However, comparing gesture use in FXS and ASIBS will help to fill this gap in literature by providing a more comprehensive understanding of communication profiles in these at-risk populations.

Purpose of current study

Gesture use is understudied and undefined in FXS, despite the fact that most children with FXS have communication deficits. Research is needed to examine early gestures use in young infants with FXS, which has implications for understanding communication development within this genetic condition, informing early identification and treatment efforts. Because FXS is not typically diagnosed until the preschool years (average age of FXS diagnosis is three years; Bailey et al., 2009), the intent of this study was to examine the gesture profiles in young infants to determine if patterns of gestures use may be a useful red flag to speed early detection. Given our focus on gesture use as a potential early risk marker for FXS, we did not control for developmental level because there is clinical value in knowing how infants with FXS compare to their same age peers. This study is aimed at filling this gap in the literature by determining whether infants with FXS exhibit differences in the frequency and function (i.e., joint attention, behavioral regulation and social interaction) of communicative gestures compared to infants with TD and ASIBS at 12 months. Data on the frequency and function of gesture use in infants with FXS will contribute to the knowledge base for a more comprehensive understanding of communication in FXS.




Participants included 18 infants with FXS, 26 infant ASIBs, and 21 typically developing infants with no family history of FXS or ASD (TD). Data were collected as part of a larger longitudinal study of the early emergence of ASD in infants with FXS, where the infants were followed from 6 to 36 months (PI: Roberts). This study presents a cross-sectional analysis of gesture use at 12 months of age; group characteristics are presented in table 1. The groups did not differ on age or proportion of males to females across the groups (ps > .500).

The ASIBs and infants with TD were recruited locally, through word of mouth, local postings and mailings to families with an identified child with ASD. Infants with FXS were recruited nationally using national listervs and collaboration among existing studies. All participants were native speakers of English and had visual and hearing acuity within the normal range, per parent report. The diagnosis of FXS was confirmed via medical review or genetic testing, and infants with FXS who had known comorbid genetic syndromes (e.g., Down syndrome) were excluded. All ASIBs had an older sibling with a clinical diagnosis of ASD and did not have any coexisting neurological or genetic conditions. Typical development was defined by full term gestation with no documented or suspected disability. To confirm the absence of developmental delays, TD infants who obtained a standard score less than 80 on the Early Learning Composite of the Mullen Scale of Early Learning (MSEL; Mullen, 1995) were excluded (n = 2). Additionally, TD infants who scored within the “at risk” range on the Autism Diagnostic Observation Schedule- Toddler (ADOS; Lord et al., 2000) at their 24 month assessment were excluded (n = 7).

Measurement of Gesture Frequency and Function

Gestures were coded from the Autism Observation Scale for Infants (AOSI; Bryson et el., 2007). The AOSI is a semi-structured play-based interaction between an examiner and an infant. The AOSI takes approximately 20 minutes to administer, although the total length may vary due to the semi-structured nature of the assessment; in this study, the AOSI length was similar across the groups (M length = 11.63 min; F (2,62) = 0.27, p = .763). Gestures were coded from the AOSI using the schema outlined by Watson et al. (2013). A checklist is used to determine if a given behavior can be considered a communicative gestural act: the behavior must (1) act as a gesture (2) be directed towards another person, and (3) serve a communicative function. Provided that the behavior meets criteria to be considered a communicative gestural act, the mode of directedness (eye contact plus vocalization, eye contact only, vocalization only, physical touch or interaction) and the function of the gesture (BR, SI or JA) is recorded. Thus, the coding schema provides information on both the frequency and the functions of the communicative gestures used during the interaction. Each sample was coded by two blinded, independent research assistants. Prior to coding, the assistants completed extensive training that included joint coding and discussion of approximately 30 training videos and establishing inter-rater reliability of > 80% agreement on three consecutive samples. Consensus scores were used in analysis, which were obtained by the assistants via discussion. Prior to consensus, the Kappa reliability statistic between the two independent raters was computed at 0.52 for BR gestures, 0.66 for SI gestures, and 0.59 for JA gestures. The following ranges of kappa statistics are useful for interpreting the relative strength of agreement: 0.21-0.40= fair, 0.41-0.60 = moderate, 0.61-0.80 = substantial (Landis & Koch, 1977).

Data Analysis

Analyses were performed using SAS 9.4 (Cary, NC). Negative binomial regression models were used to model group effects on the number of gestures used. This type of model is appropriate for discrete count data exhibiting significant positive skew and overdispersion (i.e., variance > mean). Separate models were fit for the total number of gestures, as well as the three gesture subtypes (behavior regulation, social interaction, and joint attention). A-priori contrasts were specified to test differences in gesture frequency between the FXS and ASIB groups versus TD, as well as differences between the FXS and ASIB groups. Descriptive statistics on the gesture categories (BR, SI, and JA) are presented in Table 2.



Group comparison on frequency of overall gestures

The negative binomial model indicated that infants with FXS had lower than expected rates of gestures than the infants with TD (β = -0.54, χ² = 3.87, p = .049), with the differences in the logs of expected counts 0.54 units lower for an infant with FXS compared to infants with TD. This means that for every gesture displayed by an infant with TD, an infant with FXS displays gestures at a rate .54 lower than infants with TD, such that infants with FXS are nearly half as likely to display a single gesture when compared to infants with TD. The ASIBs did not differ significantly from the infants with TD in the total number of gestures (β = -0.32, χ² = 1.92, p = .165), with logs of expected counts 0.32 units lower for the ASIBS compared to the infants with TD. Contrasts between the FXS and ASIB infant groups indicated similar rates of overall gestures across these groups (p =.410).

Group comparison on gesture function

            None of the group contrasts were significant for the frequency of behavior regulatory, social interaction, and joint attention gestures (all p’s > .205), suggesting similar rates of gesture use across the groups within these function categories.



            The results of this study contribute to the knowledge of early communication profiles of infants with FXS, ASIBS, and TD, notably, in the group comparisons of overall gesture use. The data provide clinical implications for future directions in early intervention and screenings for infants. Discrepancies between our results and previous literature focusing on the communicative functions of gestures between groups provide guidance for future studies.

The results from this study indicate infants with FXS display significantly fewer gestures than infants with TD, suggesting that infants with FXS display a distinct communication profile as early as 12 months of age Existing literature has found that both infants with FXS and ASIBS produce fewer gestures at 12 months of age than their typically developing peers (Marschik et al., 2014; Mitchel et al., 2006), however, our study indicated no significant difference of gesture frequency between the ASIBS and FXS groups. Past research has focused on gesture profiles of ASIBS who were later diagnosed with ASD. Our study included ASIBS whose ASD diagnostic outcome is unknown. With recurrence rates in ASIBS estimated at 20%, it is likely that the majority of our sample comprised of infants who will not go on to develop ASD themselves and therefore would presumably have stronger communication skills than ASIBS who are later diagnosed with ASD. It is also possible that our study was underpowered to detect effects; mean number of gestures of the ASIBS was lower than the infants with TD and similar to the mean of the infants with FXS, suggesting group differences between the ASIBS and TD infants that we may have been underpowered to detect.

Contrary to existing literature on BR functions, which supports lower frequency of BR gestures in infants with ASD, no group differences were detected in the frequency of BR functions. A possible explanation for the discrepancies between existing literature and our study is a contextual effect of the AOSI. The AOSI is a semi-structured play-based assessment that is guided by an examiner; however, the examiner is encouraged to engage in play with the infant. As a result, the infant is not given much opportunity to regulate the examiner’s behavior and is consistently encouraged to mutually interact with examiner. In line with this explanation, BR regulation gestures were seen at a low frequency across groups: no infant in our sample used more than 4 gestures with BR functions during the AOSI interaction.

Previous research examining gesture functions in infants with TD, other developmental disabilities, and ASD between 9 and 12 months were unable to detect any group differences for SI gestures (Watson et al., 2013). Our findings on the use of SI gestures were consistent with previous research on infants with TD and infants with FXS. Additionally, implications from these findings encourage the examination of potential similarities in the early communication profiles of infants with FXS and ASIBS. However, infants with TD and ASIBS displayed no difference in gestures with JA functions despite known deficits in JA gestures in infants with ASD. Although these findings are unexpected, it is possible our study did not detect differences between infants with TD and ASIBS because JA gestures typically have a low overall rate of occurrence in all infants at this time point (Watson et al., 2013). Additionally, our sample of ASIBS was not determined by an ASD diagnosis, therefore, we can assume that the majority of the ASIBS group would show similar frequencies of JA functions as the TD group.

Future Directions and Limitations

Communication impairment is well documented in FXS, however, there is limited research on the early development of communication skills. Gestures serve as one of the earliest forms of communication; yet, very few studies have studies have investigated gesture use in 12-month-old infants with direct-assessment methods. Previous studies have examined gesture profiles through the use of parent report, however, these data may not be as accurate, as they heavily rely on past memories of child behavior. The semi-structured context of the AOSI provided consistency among the sample in directly assessing gesture use. By examining gesture use at an early age, our study contributed in filling the gap in literature on early gesture use in infants, however, our study also had limitations. Weaknesses in our study were a small sample size, and our analyses were potentially underpowered. We suspect that a larger sample size would have contributed additional findings. However, our study has several implications for future research in the area of gesture development such as contributing to the understanding of early communication profiles in FXS and ASIBS

Our study excluded infants with TD who were later diagnosed with ASD according to the Autism Diagnostic Observation Scale (Rutter, DiLavore, & Risi, 2002), however, we did not exclude ASIBS who were later diagnosed with ASD. Evidence suggests that ASIBS who were later diagnosed with ASD show a lower overall frequency of gesture use and display lower BR and JA functions than ASIBS who were not later diagnosed with ASD (Mitchel et al., 2006; Rozga et al.,2011). Comparing gesture profiles of ASIBS who were later diagnosed with ASD and ASIBS who were not later diagnosed with ASD is an important direction for future studies to investigate. Future research could also compare gesture profiles of infants with FXS and ASIBS later diagnosed with ASD to determine if similarities exist. This has implications for early identification of ASD.

Our study aimed to examine the difference of gesture use between infants with FXS, TD and ASIBS. Since a diagnosis of FXS is typically unknown until around 3 years of age (Bailey, Raspa, Bishop, & Holiday, 2009), the overarching focus of our study was early detection of language delays presuming lack of diagnosis, meaning how can early gesture use inform clinicians of a potential language delay when an infant has not been diagnosed with FXS, or any disorder that impacts communication skills. Our study did not control for developmental level in our analyses, such that cognitive abilities may vary significantly in our sample. Our purpose for this was based on the intent to examine the gesture profiles at 12 months of age and to determine if gestures were useful in detecting delays since that is what a clinician would see. Future studies should examine predictors of gesture use such as developmental level. These studies would contribute to knowledge of early gesture development and aid in identifying early risk factors of ASD.




About the Author

Killian HughesKillian Hughes

I am originally from Columbia, South Carolina and I graduated from the University of South Carolina in May 2015 with a major in Experimental Psychology and a minor in Criminal Justice. During my undergraduate career I received a Magellan Scholar Research Grant to investigate early gesture use in infants with Fragile X syndrome. I was motivated to conduct this research because the goal of the study was to better inform early identification and treatment efforts, which is critical for better outcomes in children with developmental disabilities. Due to the support from Dr. Jessica Klusek and Dr. Jane Roberts in the Neurodevelopmental Disorders Lab at USC, I was able to present this research at Louisiana State University and Discovery Day at USC. Additionally, this research was presented at the 2015 ASHA Convention in Denver, Colorado. My experience as a Magellan Scholar and working with Dr. Klusek and Dr. Roberts motivated me to pursue a research career in academia. Currently, I am currently earning my Ph.D. in School Psychology at The University of Houston with a primary research interest in developmental disorders.



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