Correction: Common-variant associations with fragile X syndrome.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Common-variant associations with fragile X syndrome.

Fragile X syndrome is rare but a prominent cause of intellectual disability. It is usually caused by a de novo mutation that occurs on multiple haplotypes and thus would not be expected to be detectible using genome-wide association (GWA). We conducted GWA in 89 male FXS cases and 266 male controls, and detected multiple genome-wide significant signals near FMR1 (odds ratio = 8.10, P = 2.5 × 10-10). These findings withstood robust attempts at falsification. Fine-mapping yielded a minimum P = 1.13 × 10-14, but did not narrow the interval. Comprehensive functional genomic integration did not provide a mechanistic hypothesis. Controls carrying a risk haplotype had significantly longer FMR1 CGG repeats than controls with the protective haplotype (P = 4.75 × 10-5), which may predispose toward increases in CGG number to the premutation range over many generations. This is a salutary reminder of the complexity of even "simple" monogenetic disorders.

Longitudinal analysis of communication repair skills across three neurodevelopmental disabilities.

BACKGROUND: This study is a longitudinal follow-up to prior work examining the important pragmatic skill of communication repair (i.e., the ability to respond effectively to a request for clarification of an unclear message) across three neurodevelopmental disabilities in which language skills are impaired: fragile X syndrome with and without autism spectrum disorder (FXS-ASD; FXS-O), idiopathic ASD (ASD-O), Down syndrome (DS) and controls with typical development (TD). Prior work examining communication repair skills at younger ages indicated impairments in boys with FXS-ASD and ASD-O, with females performing comparably with each other across groups. AIMS: To characterize communication repair skills in young individuals with FXS-ASD, FXS-O, ASD-O, DS and TD, across groups and over development. A secondary aim included documenting sex differences in FXS (with and without ASD) and DS. METHODS & PROCEDURES: Sixty young individuals with FXS-ASD (49 males, 11 females), 38 with FXS-O (13 males, 25 females), 38 with ASD-O (males only), 42 with DS (21 males, 21 females) and 41 with TD (21 males, 20 females) participated in the study, with a subsample reported on here who were retested at a second time point 2.7 years later on average. Participants completed a structured, picture-based task designed to assess the ability to repair breakdowns in communication. Participants' responses were compared across groups and sexes at the second time point, and interpreted with respect to previously published (Time 1) findings. OUTCOMES & RESULTS: Key findings included that, with age, male groups (including those with FXS-ASD and ASD-O, who showed difficulty at Time 1) performed more comparably, decreasing their use of inappropriate responses, in spite of relatively little change observed in general cognitive or structural language abilities in the clinical groups. However, girls with FXS and DS became more non-responsive with age, and differences between boys and girls with FXS-ASD emerged over time as well. CONCLUSIONS & IMPLICATIONS: Findings suggest that impairments in a critical pragmatic skill-the ability to repair communication breakdown-show significant change with age across three neurodevelopmental disabilities, with important sex-specific patterns. These developments were often observed in spite of a relative plateau in cognitive and language growth, suggesting that repair skills may be more malleable and therefore an excellent target for intervention. Findings not only inform the nature of pragmatic impairment across groups but also can importantly inform clinical practice, suggesting that clinicians should monitor pragmatic skills such as repairs throughout development and also consider the role of sex in clinical efforts.

Update on the Clinical, Radiographic, and Neurobehavioral Manifestations in FXTAS and FMR1 Premutation Carriers.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a progressive neurodegenerative disorder caused by a repeat expansion in the fragile X mental retardation 1 (FMR1) gene. The disorder is characterized by kinetic tremor and cerebellar ataxia, shows age-dependent penetrance, and occurs more frequently in men. This paper summarizes the key emerging issues in FXTAS as presented at the Second International Conference on the FMR1 Premutation: Basic Mechanisms & Clinical Involvement in 2015. The topics discussed include phenotype-genotype relationships, neurobehavioral function, and updates on FXTAS genetics and imaging.

Perception of affect in biological motion cues in anorexia nervosa.

OBJECTIVE: Nonverbal motion cues (a clenched fist) convey essential information about the intentions of the actor. Individuals with anorexia nervosa (AN) have demonstrated impairment in deciphering intention from facial affective cues, but it is unknown whether such deficits extend to deciphering affect from body motion cues. METHOD: We examined the capacities of adults with AN (n = 21) or those weight restored for ≥12 months (WR; n = 20) to perceive affect in biological motion cues relative to healthy controls (HC; n = 23). RESULTS: Overall, individuals with AN evidenced greater deficit in discriminating affect from biological motion cues than WR or HC. Follow-up analyses showed that individuals with AN differed especially across two of the five conditions--deviating most from normative data when discriminating sadness and more consistently discriminating anger relative to WR or HC. DISCUSSION: Implications of these findings are discussed in relation to some puzzling interpersonal features of AN.

Longitudinal profiles of expressive vocabulary, syntax and pragmatic language in boys with fragile X syndrome or Down syndrome.

BACKGROUND: Fragile X syndrome (FXS) and Down syndrome (DS) are the two leading genetic causes of intellectual disability, and FXS is the most common known genetic condition associated with autism. Both FXS and DS are associated with significant language impairment, but little is known about expressive language across domains over time or the role of autism in language development in FXS. AIMS: To compare three domains of language production (vocabulary, syntax, pragmatics) over time within and across groups of boys with FXS with and without autism spectrum disorder (FXS-ASD, FXS-O), boys with DS, and typically developing (TD) boys. METHODS & PROCEDURES: Twenty-nine boys with FXS-O, 40 boys with FXS-ASD, 34 boys with DS, and 48 younger TD boys of similar non-verbal mental age living in the United States participated in the study. The Antonyms, Syntax Construction and Pragmatic Judgment subtests of the Comprehensive Assessment of Spoken Language were administered annually over 3 years. OUTCOMES & RESULTS: TD boys scored higher than all other groups on all three subtests; boys with FXS-O and FXS-ASD scored higher than boys with DS in Syntax Construction; and boys with FXS-O scored higher than boys with FXS-ASD in Pragmatic Judgment. Within-group patterns varied between groups. Overall, the TD group showed significantly more change over time than all other groups. CONCLUSIONS & IMPLICATIONS: Findings suggest that expressive language skills and growth across various domains are more impaired in boys with FXS and DS than would be expected based on non-verbal mental age, that for boys with DS syntax is more impaired than would be expected based on intellectual disability, and that autism status affects pragmatic language in boys with FXS. Findings suggest that language production across domains should be addressed during assessment and intervention for boys with FXS and boys with DS, with differing group profiles also suggesting potentially different areas of focus.

Differences in speech articulatory timing and associations with pragmatic language ability in autism.

Background: Speech articulation difficulties have not traditionally been considered to be a feature of Autism Spectrum Disorder (ASD). In contrast, speech prosodic differences have been widely reported in ASD, and may even be expressed in subtle form among clinically unaffected first-degree relatives, representing the expression of underlying genetic liability. Some evidence has challenged this traditional dichotomy, suggesting that differences in speech articulatory mechanisms may be evident in ASD, and potentially related to perceived prosodic differences. Clinical measurement of articulatory skills has traditionally been phoneme-based, rather than by acoustic measurement of motor control. Subtle differences in articulatory/motor control, prosodic characteristics (acoustic), and pragmatic language ability (linguistic) may each be contributors to differences perceived by listeners, but the interrelationship is unclear. In this study, we examined the articulatory aspects of this relationship, in speech samples from individuals with ASD and their parents during narration. Method: Using Speechmark® analysis, we examined articulatory landmarks, fine-grained representations of articulatory timing as series of laryngeal and vocal-tract gestures pertaining to prosodic elements crucial for conveying pragmatic information. Results: Results revealed articulatory timing differences in individuals with ASD but not their parents, suggesting that although potentially not influenced by broader genetic liability to ASD, subtle articulatory differences may indeed be evident in ASD as the recent literature indicates. A follow-up path analysis detected associations between articulatory timing differences and prosody, and subsequently, pragmatic language ability. Conclusion: Together, results suggest a complex relationship where subtle differences in articulatory timing may result in atypical acoustic signals, and serve as a distal mechanistic contributor to pragmatic language ability ASD.

[Formula: see text] A cross-cultural study of visual attention in autism spectrum disorder.

Differences in visual attention have been documented in ASD, and appear linked to clinical symptoms. However, most research has been conducted in Western cultures. Because striking differences in visual attention patterns have been documented in other cultures, it is important to understand how culture may influence attentional patterns in ASD. This study compared differences in visual attention in ASD across Western and East Asian cultures, where differences in attention to contextual and global information have been repeatedly demonstrated, to investigate potential culturally-specific ASD phenotypes. One hundred thirty-two total participants included individuals with ASD (n = 24) and controls (n = 47) from Hong Kong (HK), along with a previously studied group of age- and IQ-comparable participants from the United States (n = 26 ASD; n = 35 control). Gaze was tracked while participants completed two narrative tasks that differed in social-emotional complexity. Proportions of fixations to face, bodies, and setting were examined across groups using linear mixed-effect models and a series of growth curve models. Cultural differences were found across tasks and groups. Both the ASD and control HK groups attended more to global contextual setting information, more to the body regions, and less toward faces of characters compared to US groups. Growth curve models indicated that these differences attenuated over time in certain stimuli. ASD-related effects were only observed in the more complex stimuli depicting characters with ambiguous facial expressions. Findings indicate a notable cultural influence on visual attention patterns in ASD, and underscore the importance of stimuli complexity in differentiating cultural versus diagnostic effects on attentional styles.

A profile of prosodic speech differences in individuals with autism spectrum disorder and first-degree relatives.

BACKGROUND: Impairments in prosody (e.g., intonation, stress) are among the most notable communication characteristics of individuals with autism spectrum disorder (ASD) and can significantly impact communicative interactions. Evidence suggests that differences in prosody may be evident among first-degree relatives of autistic individuals, indicating that genetic liability to ASD is expressed through prosodic variation, along with subclinical traits referred to as the broad autism phenotype (BAP). This study aimed to further characterize prosodic profiles associated with ASD and the BAP to better understand the clinical and etiologic significance of prosodic differences. METHOD: Autistic individuals, their parents, and respective control groups completed the Profiling Elements of Prosody in Speech-Communication (PEPS-C), an assessment of receptive and expressive prosody. Responses to expressive subtests were further examined using acoustic analyses. Relationships between PEPS-C performance, acoustic measurements, and pragmatic language ability in conversation were assessed to understand how differences in prosody might contribute to broader ASD-related pragmatic profiles. RESULTS: In ASD, receptive prosody deficits were observed in contrastive stress. With regard to expressive prosody, both the ASD and ASD Parent groups exhibited reduced accuracy in imitation, lexical stress, and contrastive stress expression compared to respective control groups, though no acoustic differences were noted. In ASD and Control groups, lower accuracy across several PEPS-C subtests and acoustic measurements related to increased pragmatic language violations. In parents, acoustic measurements were tied to broader pragmatic language and personality traits of the BAP. CONCLUSION: Overlapping areas of expressive prosody differences were identified in ASD and parents, providing evidence that prosody is an important language-related ability that may be impacted by genetic risk of ASD.

A longitudinal investigation of pragmatic language across contexts in autism and related neurodevelopmental conditions.

Background: Pragmatic language, or the use of language in social contexts, is a critical skill in daily life, supporting social interactions and the development of meaningful social relationships. Pragmatic language is universally impacted in autism spectrum disorder (ASD) and pragmatic deficits are also common in other neurodevelopmental conditions, particularly those related to ASD, such as fragile X syndrome (FXS). This study used a multi-method, longitudinal approach to characterize potentially unique pragmatic profiles across different neurodevelopmental disabilities, and across contexts that varied in degree of social demand. The utility of computational linguistic analyses, as an efficient tool for capturing pragmatic abilities, was also explored. Methods: Pragmatic skills of boys with idiopathic ASD (ASD-O, n = 43), FXS with and without ASD (FXS-ASD, n = 57; FXS-O, n = 14), Down syndrome (DS, n = 22), and typical development (TD, n = 24) were compared using variables obtained from a standardized measure, narrative, and semi-naturalistic conversation at up to three time points. Results: Pragmatic language was most significantly impacted among males with ASD-O and FXS-ASD across all three contexts, with more difficulties in the least structured context (conversation), and also some differences based on FXS comorbidity. Patterns of group differences were more nuanced for boys with FXS-O and DS, with context having less of an impact. Clinical groups demonstrated minimal changes in pragmatic skills with age, with some exceptions. Computational language measurement tools showed some utility for measuring pragmatic skills, but were not as successful as traditional methods at capturing differences between clinical groups. Conclusion: Overlap and differences between ASD and other forms of neurodevelopmental disability in general, and between idiopathic and syndromic ASD in particular, have important implications for developing precisely tailored assessment and intervention approaches, consistent with a personalized medicine approach to clinical study and care in ASD.

Childhood Academic Performance: A Potential Marker of Genetic Liability to Autism.

Autism spectrum disorder (ASD), a heritable neurodevelopmental disorder, confers genetic liability that is often expressed among relatives through subclinical, genetically-meaningful traits, or endophenotypes. For instance, relative to controls, parents of individuals with ASD differ in language-related skills, with differences emerging in childhood. To examine ASD-related endophenotypes, this study investigated developmental academic profiles among clinically unaffected siblings of individuals with ASD (n = 29). Lower performance in language-related skills among siblings mirrored previously-reported patterns among parents, which were also associated with greater subclinical ASD-related traits in themselves and their parents, and with greater symptom severity in their sibling with ASD. Findings demonstrated specific phenotypes, derived from standardized academic testing, that may represent childhood indicators of genetic liability to ASD in first-degree relatives.

One size does not fit all for parent-mediated autism interventions: A randomized clinical trial.

LAY ABSTRACT: Parent-mediated interventions support parents' use of language facilitation strategies to improve their autistic child's communication and language development. To improve the effectiveness of parent-mediated interventions, it is important to individualize interventions. This article evaluates how different components of parent-mediated interventions and mothers' learning styles influence the effectiveness of the intervention. In a randomized clinical trial, mothers were taught to use one of two types of language facilitation strategies: responsive and directive. Mothers' learning styles were characterized by the Broad Autism Phenotype (BAP) and their natural tendency to use language facilitation strategies before intervention. Findings suggest that it was easier for all mothers (irrespective of learning style) to use responsive strategies compared to directive strategies. In addition, mothers with learning styles that were not consistent with the BAP were more likely to benefit from the intervention if they did not naturally use strategies before the intervention. In contrast, mothers with learning styles that were consistent with the BAP were more likely to benefit from the intervention if they did naturally use strategies before the intervention. Teaching mothers to use responsive strategies results in greater strategy use. Consideration of BAP and mothers' natural use of language facilitation strategies may inform intervention individualization.

Neural Processing of Speech Sounds in ASD and First-Degree Relatives.

Efficient neural encoding of sound plays a critical role in speech and language, and when impaired, may have reverberating effects on communication skills. This study investigated disruptions to neural processing of temporal and spectral properties of speech in individuals with ASD and their parents and found evidence of inefficient temporal encoding of speech sounds in both groups. The ASD group further demonstrated less robust neural representation of spectral properties of speech sounds. Associations between neural processing of speech sounds and language-related abilities were evident in both groups. Parent-child associations were also detected in neural pitch processing. Together, results suggest that atypical neural processing of speech sounds is a heritable ingredient contributing to the ASD language phenotype.

Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on FMR1 Premutation.

The premutation of the fragile X messenger ribonucleoprotein 1 (FMR1) gene is characterized by an expansion of the CGG trinucleotide repeats (55 to 200 CGGs) in the 5' untranslated region and increased levels of FMR1 mRNA. Molecular mechanisms leading to fragile X-premutation-associated conditions (FXPAC) include cotranscriptional R-loop formations, FMR1 mRNA toxicity through both RNA gelation into nuclear foci and sequestration of various CGG-repeat-binding proteins, and the repeat-associated non-AUG (RAN)-initiated translation of potentially toxic proteins. Such molecular mechanisms contribute to subsequent consequences, including mitochondrial dysfunction and neuronal death. Clinically, premutation carriers may exhibit a wide range of symptoms and phenotypes. Any of the problems associated with the premutation can appropriately be called FXPAC. Fragile X-associated tremor/ataxia syndrome (FXTAS), fragile X-associated primary ovarian insufficiency (FXPOI), and fragile X-associated neuropsychiatric disorders (FXAND) can fall under FXPAC. Understanding the molecular and clinical aspects of the premutation of the FMR1 gene is crucial for the accurate diagnosis, genetic counseling, and appropriate management of affected individuals and families. This paper summarizes all the known problems associated with the premutation and documents the presentations and discussions that occurred at the International Premutation Conference, which took place in New Zealand in 2023.

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.

A constellation of eye-tracking measures reveals social attention differences in ASD and the broad autism phenotype.

BACKGROUND: Social attention differences, expressed through gaze patterns, have been documented in autism spectrum disorder (ASD), with subtle differences also reported among first-degree relatives, suggesting a shared genetic link. Findings have mostly been derived from standard eye-tracking methods (total fixation count or total fixation duration). Given the dynamics of visual attention, these standard methods may obscure subtle, yet core, differences in visual attention mechanisms, particularly those presenting sub-clinically. This study applied a constellation of eye-tracking analyses to gaze data from individuals with ASD and their parents. METHODS: This study included n = 156 participants across groups, including ASD (n = 24) and control (n = 32) groups, and parents of individuals with ASD (n = 61) and control parents (n = 39). A complex scene with social/non-social elements was displayed and gaze tracked via an eye tracker. Eleven analytic methods from the following categories were analyzed: (1) standard variables, (2) temporal dynamics (e.g., gaze over time), (3) fixation patterns (e.g., perseverative or regressive fixations), (4) first fixations, and (5) distribution patterns. MANOVAs, growth curve analyses, and Chi-squared tests were applied to examine group differences. Finally, group differences were examined on component scores derived from a principal component analysis (PCA) that reduced variables to distinct dimensions. RESULTS: No group differences emerged among standard, first fixation, and distribution pattern variables. Both the ASD and ASD parent groups demonstrated on average reduced social attention over time and atypical perseverative fixations. Lower social attention factor scores derived from PCA strongly differentiated the ASD and ASD parent groups from controls, with parent findings driven by the subset of parents demonstrating the broad autism phenotype. LIMITATIONS: To generalize these findings, larger sample sizes, extended viewing contexts (e.g., dynamic stimuli), and even more eye-tracking analytical methods are needed. CONCLUSIONS: Fixations over time and perseverative fixations differentiated ASD and the ASD parent groups from controls, with the PCA most robustly capturing social attention differences. Findings highlight their methodological utility in studies of the (broad) autism spectrum to capture nuanced visual attention differences that may relate to clinical symptoms in ASD, and reflect genetic liability in clinically unaffected relatives. This proof-of-concept study may inform future studies using eye tracking across populations where social attention is impacted.

Slower Peak Pupillary Response to Emotional Faces in Parents of Autistic Individuals.

Background: Atypical autonomic arousal has been consistently documented in autism spectrum disorder (ASD) and is thought to contribute to the social-communication phenotype of ASD. Some evidence suggests that clinically unaffected first-degree relatives of autistic individuals may also show subtle differences in indices of autonomic arousal, potentially implicating heritable pathophysiological mechanisms in ASD. This study examined pupillary responses in parents of autistic individuals to investigate evidence that atypical autonomic arousal might constitute a subclinical physiological marker of ASD heritability within families of autistic individuals. Methods: Pupillary responses to emotional faces were measured in 47 ASD parents and 20 age-matched parent controls. Macro-level pupillary responses (e.g., mean, peak, latency to peak) and dynamic pupillary responses over the course of the stimulus presentation were compared between groups, and in relationship to subclinical ASD-related features in ASD parents. A small ASD group (n = 20) and controls (n = 17) were also included for exploratory analyses of parent-child correlations in pupillary response. Results: Parents of autistic individuals differed in the time course of pupillary response, exhibiting a later primary peak response than controls. In ASD parents, slower peak response was associated with poorer pragmatic language and larger peak response was associated with poorer social cognition. Exploratory analyses revealed correlations between peak pupillary responses in ASD parents and mean and peak pupillary responses in their autistic children. Conclusion: Differences in pupillary responses in clinically unaffected parents, together with significant correlations with ASD-related features and significant parent-child associations, suggest that pupillary responses to emotional faces may constitute an objective physiological marker of ASD genetic liability, with potential to inform the mechanistic underpinnings of ASD symptomatology.

Verbal entrainment in autism spectrum disorder and first-degree relatives.

Entrainment, the unconscious process leading to coordination between communication partners, is an important dynamic human behavior that helps us connect with one another. Difficulty developing and sustaining social connections is a hallmark of autism spectrum disorder (ASD). Subtle differences in social behaviors have also been noted in first-degree relatives of autistic individuals and may express underlying genetic liability to ASD. In-depth examination of verbal entrainment was conducted to examine disruptions to entrainment as a contributing factor to the language phenotype in ASD. Results revealed distinct patterns of prosodic and lexical entrainment in individuals with ASD. Notably, subtler entrainment differences in prosodic and syntactic entrainment were identified in parents of autistic individuals. Findings point towards entrainment, particularly prosodic entrainment, as a key process linked to social communication difficulties in ASD and reflective of genetic liability to ASD.

Cross-linguistic patterns of speech prosodic differences in autism: A machine learning study.

Differences in speech prosody are a widely observed feature of Autism Spectrum Disorder (ASD). However, it is unclear how prosodic differences in ASD manifest across different languages that demonstrate cross-linguistic variability in prosody. Using a supervised machine-learning analytic approach, we examined acoustic features relevant to rhythmic and intonational aspects of prosody derived from narrative samples elicited in English and Cantonese, two typologically and prosodically distinct languages. Our models revealed successful classification of ASD diagnosis using rhythm-relative features within and across both languages. Classification with intonation-relevant features was significant for English but not Cantonese. Results highlight differences in rhythm as a key prosodic feature impacted in ASD, and also demonstrate important variability in other prosodic properties that appear to be modulated by language-specific differences, such as intonation.

A Longitudinal Study of Parent-Child Interactions and Language Outcomes in Fragile X Syndrome and Other Neurodevelopmental Disorders.

Difficulties with pragmatic language (i.e., language in social contexts, such as conversational ability) are a noted characteristic of the language profiles of both fragile X syndrome (FXS) and autism spectrum disorder (ASD), conditions which show significant phenotypic overlap. Understanding the origins and developmental course of pragmatic language problems in FXS and other developmental conditions associated with language impairment is a critical step for the development of targeted interventions to promote communicative competence across the lifespan. This study examined pragmatic language in the context of parent-child interactions in school-age children with FXS (who did and did not meet ASD criteria on the ADOS; n = 85), idiopathic ASD (n = 32), Down syndrome (DS; n = 38), and typical development (TD; n = 39), and their parents. Parent-child communicative interactions were examined across multiple contexts, across groups, and in relationship to pragmatic language outcomes assessed 2 years later. Results showed both overlapping and divergent patterns across the FXS-ASD and idiopathic ASD child and parent groups, and also highlighted key differences in pragmatic profiles based on situational context, with more pragmatic language difficulties occurring for both ASD groups in less structured interactions. Differences in parental language styles during parent-child interactions were associated with child language outcomes, likely reflecting the complex interplay of discourse style inherent to a parent, with the inevitable influence of child characteristics on parent language as well. Together, findings help delineate the dynamic and multifactorial nature of impaired pragmatic skills among children with FXS and other neurodevelopmental disorders associated with language impairment, with potential implications for the development of targeted interventions for pragmatic communication skills.