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This study characterized the rates of attention-deficit/hyperactivity disorder (ADHD) in adolescent and young adult males with fragile X syndrome (FXS) using a multi-method approach integrating a DSM-based parent interview (Children's Interview for Psychiatric Syndromes; P-ChIPS, Fristad et al., 1998) and a parent rating scale (Child Behavior Checklist; CBCL, Achenbach, 2001). Thirty-one males with FXS, aged 16-24 years, participated. Forty-two percent met DSM-5 criteria for ADHD and 35% exceeded the CBCL cut-offs. Agreement between the two classification methods was fair ([kappa] = 0.38). Autism symptom severity and nonverbal cognitive ability did not predict ADHD diagnoses/symptoms. Results show high rates of ADHD in males with FXS during late adolescence and young adulthood, which are not accounted for by impaired nonverbal cognitive skills or autism symptom severity. DSM-based ADHD-specific scales are recommended over broadband symptom scales to improve accurate identification.

Purpose: Cluttering is a fluency disorder that has been noted clinically in individuals with fragile X syndrome (FXS). Yet, cluttering has not been systematically characterized in this population, hindering identification and intervention efforts. This study examined the rates of cluttering in male young adults with FXS using expert clinical opinion, the alignment between expert clinical opinion and objectively quantified features of cluttering from language transcripts, and the association between cluttering and aspects of the FXS phenotype. Method: Thirty-six men with FXS (aged 18-26 years; M = 22, SD = 2.35) contributed language samples and completed measures of nonverbal cognition, autism symptoms, anxiety, and symptoms of attention-deficit/hyperactivity disorder (ADHD). The presence of cluttering was determined by the consensus of two clinical experts in fluency disorders based on characteristics exhibited in the language sample. Cluttering features (speech rate, disfluencies, etc.) were also objectively quantified from the language transcripts. Results: Clinical experts determined that 50% of participants met the criteria for a cluttering diagnosis. Phrase repetitions were the most salient feature that distinguished individuals who cluttered. Although the presence of cluttering was not associated with autism symptoms or mean length of utterance, cluttering was more likely to occur when nonverbal cognitive ability was higher, ADHD symptoms were elevated, and anxiety symptoms were low. Conclusions: Half of the male young adults with FXS exhibited cluttering, which supports FXS as a genetic diagnosis that is highly enriched for risk of cluttering. Cluttering was associated with increased ADHD symptoms and cognitive ability and reduced anxiety symptoms. This study contributes a new description of the clinical presentation of cluttering in men with FXS and may lead to improved understanding of the potential underlying mechanisms of cluttering and eventual refinements to treatment and diagnosis.

Broader phenotypes associated with genetic liability, including mild difficulties with pragmatic language skills, have been documented in mothers of children with autism spectrum disorder (ASD) and mothers of children with fragile X syndrome (FXS). This study investigated the relationship between pragmatic difficulties and indicators of maternal well-being and family functioning. Pragmatic difficulty was associated with loneliness in mothers of children with ASD or FXS, and with depression, decreased life satisfaction, and poorer family relationship quality in mothers of children with FXS only. Results inform subtle maternal pragmatic language difficulties as a risk factor that that may contribute to reduced health and well-being, informing tailored support services to better meet the unique needs of families of children with ASD or FXS.

By adulthood, most males with fragile X syndrome (FXS) require support to navigate day-to-day settings. The present study cross-sectionally: (1) characterized the profile of daily living skills in males with FXS and (2) examined associated participant characteristics (i.e., fragile X mental retardation protein [FMRP] expression, nonverbal cognition, language, autism symptomatology, and anxiety symptomatology) using the Waisman Activities of Daily Living questionnaire. Males with FXS (n = 57, ages 15-23 years) needed more help/support in the areas of domestic and community daily livings skills, than in the area of personal daily living skills. Significant associations were observed between reduced daily living skills and lower nonverbal cognition, receptive language, expressive language, and increased autism symptomatology. Receptive language emerged as the strongest unique predictor of daily living skill performance.

A subset of mothers who carry the "FMR1" premutation may express a unique phenotype. The relationship between the "FMR1" phenotype and mother-child interaction in families with fragile X-associated disorders has not been well characterized, despite the importance of high-quality mother-child interaction for child development. This study examined the association between the "FMR1" phenotype and the quality of interactions between mothers and their adolescent/young adult sons with fragile X syndrome. Mother-youth synchrony was coded from a dyadic interaction. Maternal anxiety and depression symptoms, executive function deficits, and pragmatic language difficulties were evaluated. Results indicated that pragmatic language was associated with mother-youth synchrony. These findings highlight the importance of family-centered intervention practices for families with fragile X-associated disorders.

Broader phenotypes associated with genetic liability, including mild difficulties with pragmatic language skills, have been documented in mothers of children with autism spectrum disorder (ASD) and mothers of children with fragile X syndrome (FXS). This study investigated the relationship between pragmatic difficulties and indicators of maternal well-being and family functioning. Pragmatic difficulty was associated with loneliness in mothers of children with ASD or FXS, and with depression, decreased life satisfaction, and poorer family relationship quality in mothers of children with FXS only. Results inform subtle maternal pragmatic language difficulties as a risk factor that that may contribute to reduced health and well-being, informing tailored support services to better meet the unique needs of families of children with ASD or FXS., Author(s): Jessica Klusek [sup.1] , Angela John Thurman [sup.2] , Leonard Abbeduto [sup.2] Author Affiliations: (1) grid.254567.7, 0000 0000 9075 106X, Department of Communication Sciences and Disorders, University of South [...]

Purpose: Infant siblings of children with autism spectrum disorder (ASIBs) and infants with fragile X syndrome (FXS) are both at risk for developing autism spectrum disorder (ASD) and communication disorders; however, very few studies have examined 1 of the earliest forms of intentional communication in infants from these groups: gestures. This study examined the frequency and function of gesture use across 12-month-old infant ASIBs, infants with FXS, and low-risk controls. Method: Participants included 23 ASIBs who did not later meet diagnostic criteria for ASD, 18 infants with FXS, and 21 low-risk controls. Gestures were coded from a semistructured play-based interaction. Results: Overall, infants with FXS displayed fewer gestures than low-risk infants, whereas ASIBs did not differ from the FXS or low-risk groups in overall gesture frequency. In terms of the communicative function of the gestures used, the FXS and ASIB groups displayed significantly fewer social interaction gestures than the low-risk controls, with large effect sizes. Conclusion: This study contributes to scant knowledge of early communication phenotypes of infant ASIBs who do not meet criteria for ASD and infants with FXS. Results indicated that gesture function, not frequency, best discriminated at-risk infants from low-risk infants at 12 months of age. Findings have implications for the clinical evaluation and treatment of infants at high risk for ASD and communication disorders.

Many males with FXS meet criteria for ASD. This study was designed to (1) describe ASD symptoms in adolescent and young adult males with FXS (n = 44) and (2) evaluate the contributions to ASD severity of cognitive, language, and psychiatric factors, as well as FMRP (the protein deficient in FXS). A few ASD symptoms on the ADOS-2 were universal in the sample. There was less impairment in restricted and repetitive behaviors (RRB) than in the social affective (SA) domain. The best predictor of overall ASD severity and SA severity was expressive syntactic ability. RRB severity was best predicted by the psychiatric factors. Implications for clinical practice and for understanding the ASD comorbidity in FXS are discussed.

Anxiety disorders affect ~ 15-20% of youths without neurodevelopmental disorders, with persons having autism spectrum disorder (ASD) and fragile X syndrome (FXS) at elevated risk for anxiety disorders. Few studies have compared rates and predictors of anxiety disorders in adolescents with FXS or ASD. This study directly compares rates, predictors, and medication of anxiety disorders between age-matched, male adolescents with FXS (n = 31) or ASD (n = 20). Results indicate that 51.6% of FXS and 50.0% of ASD adolescents met criteria for an anxiety disorder. Cognitive scores and ASD severity did not predict anxiety. Of those with anxiety, ~ 40% of the FXS and 20% of the ASD participants were prescribed medications for anxiety.

Pragmatic language skills exist across a continuum in typical and clinical populations, and are impaired in many neurodevelopmental disorders, most notably autism. The mechanisms underlying pragmatic impairment are poorly understood, although theory suggests dampened vagal tone plays a role. This study investigated the "FMR1" premutation as a genetic model that may lend insight into the relationship between vagal function and pragmatic ability. Participants included 38 women with the "FMR1" premutation and 23 controls. Vagal tone accounted for significant variance in pragmatics across both groups and statistically mediated the effect of "FMR1" premutation status on pragmatic ability. Results support vagal tone as a biophysiological correlate of pragmatic ability, which informs potential mechanistic underpinnings and could have implications for targeted treatment.

Purpose: Pragmatic language skills are often impaired above and beyond general language delays in individuals with neurodevelopmental disabilities. This study used a multimethod approach to language sample analysis to characterize syndrome- and sex-specific profiles across different neurodevelopmental disabilities and to examine the congruency of 2 analysis techniques.Method: Pragmatic skills of young males and females with fragile X syndrome with autism spectrum disorder (FXS-ASD, n = 61) and without autism spectrum disorder (FXS-O, n = 40), Down syndrome (DS, n = 42), and typical development (TD, n = 37) and males with idiopathic autism spectrum disorder only (ASD-O, n = 29) were compared using variables obtained from a detailed hand-coding system contrasted with similar variables obtained automatically from the language analysis program Systematic Analysis of Language Transcripts (SALT).Results: Noncontingent language and perseveration were characteristic of the pragmatic profiles of boys and girls with FXS-ASD and boys with ASD-O. Boys with ASD-O also initiated turns less often and were more nonresponsive than other groups, and girls with FXS-ASD were more nonresponsive than their male counterparts. Hand-coding and SALT methods were largely convergent with some exceptions.Conclusion: Results suggest both similarities and differences in the pragmatic profiles observed across different neurodevelopmental disabilities, including idiopathic and FXS-associated cases of ASD, as well as an important sex difference in FXS-ASD. These findings and congruency between the 2 language sample analysis techniques together have important implications for assessment and intervention efforts.

Purpose: The Fragile X Messenger Ribonucleoprotein-1 (FMR1) premutation (FXpm) is a genetic variant that is common in the general population and is associated with health symptoms and disease in adulthood. However, poor understanding of the clinical phenotype during childhood has hindered the development of clinical practice guidelines for screening and intervention. Given that social communication difficulties have been widely documented in adults with the FXpm and are linked with reduced psychosocial functioning, the present study aimed to characterize the communication profile of the FXpm during early childhood. Method: Eighteen children with the FXpm who were identified through cascade testing (89%) or screening at birth (11%) were compared to 21 matched typically developing children, aged 2–4 years. Participants completed standardized assessments of language (Mullen Scales of Early Learning) and adaptive communication (Vineland Adaptive Behavior Scales-II). Social communication was rated from seminaturalistic interaction samples using the Brief Observation of Social Communication Change. Results: Children with the FXpm showed delayed social communication development, with the magnitude of group differences highlighting social communication as a feature that distinguishes children with the FXpm from their peers (p= .046, ηp ² = .12). The groups did not differ on the standardized language and adaptive communication measures (ps > .297, ηp ² s < .03). Conclusions: Early screening and treatment of social communication delays may be key to optimizing outcomes for children with the FXpm. Further research is needed to replicate findings in a larger sample, delineate the trajectory and consequences of social communication difficulties across the life span in the FXpm, and determine the potential epidemiological significance of FMR1 as a mediator of developmental communication differences within the general population. [ABSTRACT FROM AUTHOR]

Individuals with fragile X syndrome (FXS) present with significant deficits in reading skills, but scant research exists to understand the characteristics of the reading delays or best practices for reading instruction with this population. Study 1 examined the relationship between phonological awareness and reading skills in individuals with FXS. Study 2 evaluated the feasibility of a web-based reading intervention, which incorporated phonological awareness and phonics instruction but was originally developed for mainstream students, for children with FXS. Results suggest that phonological awareness and reading skills are correlated in this population, and that instruction targeting phonological awareness and phonics should not be ruled out for individuals with FXS. Further studies are needed to examine their potential effects.

Effortful control, or the ability to suppress a dominant response to perform a subdominant response, is an early-emerging temperament trait that is linked with positive social-emotional development. Fragile X syndrome (FXS) is a single-gene disorder characterized by hallmark regulatory impairments, suggesting diminished effortful control. This study compared the development of effortful control in preschool boys with FXS (n = 97) and typical development (n = 32). Unlike their typical peers, the boys with FXS did not exhibit growth in effortful control over time, which could not be accounted for by adaptive impairments, FMR1 molecular measures, or autism symptoms. These results contribute to our understanding of the childhood phenotype of FXS that may be linked to the poor social-emotional outcomes seen in this group.

This longitudinal study examined pragmatic language in boys and girls with Down syndrome (DS) at up to three time points, using parent report, standardized and direct assessments. We also explored relationships among theory of mind, executive function, nonverbal mental age, receptive and expressive vocabulary, grammatical complexity, and pragmatic competence. Controlling for cognitive and language abilities, children with DS demonstrated greater difficulty than younger typically developing controls on parent report and standardized assessments, but only girls with DS differed on direct assessments. Further, pragmatic skills of individuals with DS developed at a delayed rate relative to controls. Some sex-specific patterns of pragmatic impairments emerged. Theory of mind and executive function both correlated with pragmatic competence. Clinical and theoretical implications are discussed.

Genetic liability to autism spectrum disorder (ASD) can be expressed in unaffected relatives through subclinical, genetically meaningful traits, or endophenotypes. This study aimed to identify developmental endophenotypes in parents of individuals with ASD by examining parents' childhood academic development over the school-age period. A cohort of 139 parents of individuals with ASD were studied, along with their children with ASD and 28 controls. Parents' childhood records in the domains of language, reading, and math were studied from grades K-12. Results indicated that relatively lower performance and slower development of skills (particularly language related skills), and an uneven rate of development across domains predicted ASD endophenotypes in adulthood for parents, and the severity of clinical symptoms in children with ASD. These findings may mark childhood indicators of genetic liability to ASD in parents, that could inform understanding of the subclinical expression of ASD genetic liability.

Anxiety disorders affect ~ 15-20% of youths without neurodevelopmental disorders, with persons having autism spectrum disorder (ASD) and fragile X syndrome (FXS) at elevated risk for anxiety disorders. Few studies have compared rates and predictors of anxiety disorders in adolescents with FXS or ASD. This study directly compares rates, predictors, and medication of anxiety disorders between age-matched, male adolescents with FXS (n = 31) or ASD (n = 20). Results indicate that 51.6% of FXS and 50.0% of ASD adolescents met criteria for an anxiety disorder. Cognitive scores and ASD severity did not predict anxiety. Of those with anxiety, ~ 40% of the FXS and 20% of the ASD participants were prescribed medications for anxiety., Author(s): Jordan Ezell [sup.1] , Abigail Hogan [sup.1] , Amanda Fairchild [sup.1] , Kimberly Hills [sup.1] , Jessica Klusek [sup.2] , Leonard Abbeduto [sup.3] , Jane Roberts [sup.1] Author Affiliations: [...]

Many males with FXS meet criteria for ASD. This study was designed to (1) describe ASD symptoms in adolescent and young adult males with FXS (n = 44) and (2) evaluate the contributions to ASD severity of cognitive, language, and psychiatric factors, as well as FMRP (the protein deficient in FXS). A few ASD symptoms on the ADOS-2 were universal in the sample. There was less impairment in restricted and repetitive behaviors (RRB) than in the social affective (SA) domain. The best predictor of overall ASD severity and SA severity was expressive syntactic ability. RRB severity was best predicted by the psychiatric factors. Implications for clinical practice and for understanding the ASD comorbidity in FXS are discussed., Author(s): Leonard Abbeduto [sup.1] [sup.4] , Angela John Thurman [sup.1] , Andrea McDuffie [sup.1] , Jessica Klusek [sup.2] , Robyn Tempero Feigles [sup.1] , W. Ted Brown [sup.3] , Danielle [...]

Pragmatic language skills exist across a continuum in typical and clinical populations, and are impaired in many neurodevelopmental disorders, most notably autism. The mechanisms underlying pragmatic impairment are poorly understood, although theory suggests dampened vagal tone plays a role. This study investigated the FMR1 premutation as a genetic model that may lend insight into the relationship between vagal function and pragmatic ability. Participants included 38 women with the FMR1 premutation and 23 controls. Vagal tone accounted for significant variance in pragmatics across both groups and statistically mediated the effect of FMR1 premutation status on pragmatic ability. Results support vagal tone as a biophysiological correlate of pragmatic ability, which informs potential mechanistic underpinnings and could have implications for targeted treatment., Author(s): Jessica Klusek [sup.1], Amanda J. Fairchild [sup.2], Jane E. Roberts [sup.2] Author Affiliations: (1) 0000 0000 9075 106X, grid.254567.7, Department of Communication Sciences and Disorders, University of South Carolina, [...]

Purpose: Pragmatic language skills are often impaired above and beyond general language delays in individuals with neurodevelopmental disabilities. This study used a multimethod approach to language sample analysis to characterize syndrome- and sex-specific profiles across different neurodevelopmental disabilities and to examine the congruency of 2 analysis techniques.Method: Pragmatic skills of young males and females with fragile X syndrome with autism spectrum disorder (FXS-ASD, n = 61) and without autism spectrum disorder (FXS-O, n = 40), Down syndrome (DS, n = 42), and typical development (TD, n = 37) and males with idiopathic autism spectrum disorder only (ASD-O, n = 29) were compared using variables obtained from a detailed hand-coding system contrasted with similar variables obtained automatically from the language analysis program Systematic Analysis of Language Transcripts (SALT).Results: Noncontingent language and perseveration were characteristic of the pragmatic profiles of boys and girls with FXS-ASD and boys with ASD-O. Boys with ASD-O also initiated turns less often and were more nonresponsive than other groups, and girls with FXS-ASD were more nonresponsive than their male counterparts. Hand-coding and SALT methods were largely convergent with some exceptions.Conclusion: Results suggest both similarities and differences in the pragmatic profiles observed across different neurodevelopmental disabilities, including idiopathic and FXS-associated cases of ASD, as well as an important sex difference in FXS-ASD. These findings and congruency between the 2 language sample analysis techniques together have important implications for assessment and intervention efforts., Pragmatic aspects of communication encompass a broad range of linguistic, nonlinguistic, and paralinguistic skills, including topic maintenance, turn taking, and speech acts, as well as nonverbal communication (e.g., gestures) and [...]

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 child's 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.

Although reading skills are critical for the success of individuals with intellectual disabilities, literacy has received little attention in fragile X syndrome (FXS). This study examined the literacy profile of FXS. Boys with FXS (n = 51; mean age 10.2 years) and mental age-matched boys with typical development (n = 35) participated in standardized assessments of reading and phonological skills. Phonological skills were impaired in FXS, while reading was on-par with that of controls. Phonological awareness predicted reading ability and ASD severity predicted poorer phonological abilities in FXS. Boys with FXS are capable of attaining reading skills that are commensurate with developmental level and phonological awareness skills may play a critical role in reading achievement in FXS.

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.

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. [ABSTRACT FROM AUTHOR]

Genetic liability to autism spectrum disorder (ASD) can be expressed in unaffected relatives through subclinical, genetically meaningful traits, or endophenotypes. This study aimed to identify developmental endophenotypes in parents of individuals with ASD by examining parents' childhood academic development over the school-age period. A cohort of 139 parents of individuals with ASD were studied, along with their children with ASD and 28 controls. Parents' childhood records in the domains of language, reading, and math were studied from grades K-12. Results indicated that relatively lower performance and slower development of skills (particularly language related skills), and an uneven rate of development across domains predicted ASD endophenotypes in adulthood for parents, and the severity of clinical symptoms in children with ASD. These findings may mark childhood indicators of genetic liability to ASD in parents, that could inform understanding of the subclinical expression of ASD genetic liability., Author(s): Molly Losh [sup.1] , Gary E. Martin [sup.2] , Michelle Lee [sup.1] , Jessica Klusek [sup.3] , John Sideris [sup.4] , Sheila Barron [sup.5] , Thomas Wassink [sup.6] Author [...]

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.

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.

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 child's 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., Fragile X syndrome is the most common inherited form of intellectual disability (Crawford, Acuna, & Sherman, 2001). The disorder is caused by an inherited mutation on the fragile X mental [...]

Purpose: Infant siblings of children with autism spectrum disorder (ASIBs) and infants with fragile X syndrome (FXS) are both at risk for developing autism spectrum disorder (ASD) and communication disorders; however, very few studies have examined 1 of the earliest forms of intentional communication in infants from these groups: gestures. This study examined the frequency and function of gesture use across 12-month-old infant ASIBs, infants with FXS, and low-risk controls. Method: Participants included 23 ASIBs who did not later meet diagnostic criteria for ASD, 18 infants with FXS, and 21 low-risk controls. Gestures were coded from a semistructured play-based interaction. Results: Overall, infants with FXS displayed fewer gestures than low-risk infants, whereas ASIBs did not differ from the FXS or low-risk groups in overall gesture frequency. In terms of the communicative function of the gestures used, the FXS and ASIB groups displayed significantly fewer social interaction gestures than the low-risk controls, with large effect sizes. Conclusion: This study contributes to scant knowledge of early communication phenotypes of infant ASIBs who do not meet criteria for ASd and infants with FXS. Results indicated that gesture function, not frequency, best discriminated at-risk infants from low-risk infants at 12 months of age. Findings have implications for the clinical evaluation and treatment of infants at high risk for ASD and communication disorders., Gestures emerge as early as 6-9 months of age and represent one of the first forms of intentional communication (Crais, Douglas, & Campbell, 2004). Gestures almost always precede the use [...]

Although reading skills are critical for the success of individuals with intellectual disabilities, literacy has received little attention in fragile X syndrome (FXS). This study examined the literacy profile of FXS. Boys with FXS (n = 51; mean age 10.2 years) and mental age-matched boys with typical development (n = 35) participated in standardized assessments of reading and phonological skills. Phonological skills were impaired in FXS, while reading was on-par with that of controls. Phonological awareness predicted reading ability and ASD severity predicted poorer phonological abilities in FXS. Boys with FXS are capable of attaining reading skills that are commensurate with developmental level and phonological awareness skills may play a critical role in reading achievement in FXS., Author(s): Jessica Klusek[sup.1] , Anna W. Hunt[sup.2] , Penny L. Mirrett[sup.3] , Deborah D. Hatton[sup.4] , Stephen R. Hooper[sup.5] , Jane E. Roberts[sup.6] , Donald B. Bailey[sup.7] Author Affiliations: (1) [...]

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. Key Words: pragmatic language, social communication, autism, fragile X syndrome, discourse, endophenotype, Pragmatic language competence, or the ability to use language in social contexts, is critical for supporting fluent social interactions (Bates, 1976; McTear & Conti-Ramsden, 1992; Prutting, 1982). Examples of pragmatic [...]

This study characterized the rates of attention-deficit/hyperactivity disorder (ADHD) in adolescent and young adult males with fragile X syndrome (FXS) using a multi-method approach integrating a DSM-based parent interview (Children's Interview for Psychiatric Syndromes; P-ChIPS, Fristad et al., 1998) and a parent rating scale (Child Behavior Checklist; CBCL, Achenbach, 2001). Thirty-one males with FXS, aged 16-24 years, participated. Forty-two percent met DSM-5 criteria for ADHD and 35% exceeded the CBCL cut-offs. Agreement between the two classification methods was fair (κ = 0.38). Autism symptom severity and nonverbal cognitive ability did not predict ADHD diagnoses/symptoms. Results show high rates of ADHD in males with FXS during late adolescence and young adulthood, which are not accounted for by impaired nonverbal cognitive skills or autism symptom severity. DSM-based ADHD-specific scales are recommended over broadband symptom scales to improve accurate identification. [ABSTRACT FROM AUTHOR]

Purpose: Cluttering is a fluency disorder that has been noted clinically in individuals with fragile X syndrome (FXS). Yet, cluttering has not been systematically characterized in this population, hindering identification and intervention efforts. This study examined the rates of cluttering in male young adults with FXS using expert clinical opinion, the alignment between expert clinical opinion and objectively quantified features of cluttering from language transcripts, and the association between cluttering and aspects of the FXS phenotype. Method: Thirty-six men with FXS (aged 18–26 years; M = 22, SD = 2.35) contributed language samples and completed measures of nonverbal cognition, autism symptoms, anxiety, and symptoms of attention-deficit/hyperactivity disorder (ADHD). The presence of cluttering was determined by the consensus of two clinical experts in fluency disorders based on characteristics exhibited in the language sample. Cluttering features (speech rate, disfluencies, etc.) were also objectively quantified from the language transcripts. Results: Clinical experts determined that 50% of participants met the criteria for a cluttering diagnosis. Phrase repetitions were the most salient feature that distinguished individuals who cluttered. Although the presence of cluttering was not associated with autism symptoms or mean length of utterance, cluttering was more likely to occur when nonverbal cognitive ability was higher, ADHD symptoms were elevated, and anxiety symptoms were low. Conclusions: Half of the male young adults with FXS exhibited cluttering, which supports FXS as a genetic diagnosis that is highly enriched for risk of cluttering. Cluttering was associated with increased ADHD symptoms and cognitive ability and reduced anxiety symptoms. This study contributes a new description of the clinical presentation of cluttering in men with FXS and may lead to improved understanding of the potential underlying mechanisms of cluttering and eventual refinements to treatment and diagnosis. [ABSTRACT FROM AUTHOR]

By adulthood, most males with fragile X syndrome (FXS) require support to navigate day-to-day settings. The present study cross-sectionally: (1) characterized the profile of daily living skills in males with FXS and (2) examined associated participant characteristics (i.e., fragile X mental retardation protein [FMRP] expression, nonverbal cognition, language, autism symptomatology, and anxiety symptomatology) using the Waisman-Activities of Daily Living questionnaire. Males with FXS (n = 57, ages 15-23 years) needed more help/support in the areas of domestic and community daily livings skills, than in the area of personal daily living skills. Significant associations were observed between reduced daily living skills and lower nonverbal cognition, receptive language, expressive language, and increased autism symptomatology. Receptive language emerged as the strongest unique predictor of daily living skill performance. [ABSTRACT FROM AUTHOR]

A subset of mothers who carry the FMR1 premutation may express a unique phenotype. The relationship between the FMR1 phenotype and mother-child interaction in families with fragile X-associated disorders has not been well characterized, despite the importance of high-quality mother-child interaction for child development. This study examined the association between the FMR1 phenotype and the quality of interactions between mothers and their adolescent/young adult sons with fragile X syndrome. Mother-youth synchrony was coded from a dyadic interaction. Maternal anxiety and depression symptoms, executive function deficits, and pragmatic language difficulties were evaluated. Results indicated that pragmatic language was associated with mother-youth synchrony. These findings highlight the importance of family-centered intervention practices for families with fragile X-associated disorders. [ABSTRACT FROM AUTHOR]

Background: Fragile X syndrome (FXS) is a monogenic disorder characterized by high rates of autism spectrum disorder (ASD) and anxiety. A longstanding "hyperarousal hypothesis" in FXS has argued that ANS dysfunction underpins many symptoms of FXS. However, the developmental onset and trajectory of ANS dysfunction, as well as the consequences of ANS dysfunction on later psychiatric symptoms, remain poorly understood in FXS. Insight into the emergence, trajectory, and consequences of ANS dysfunction across early development in FXS has critical implications for prevention, intervention, and optimal outcomes in both typical and atypical development. This longitudinal study investigated whether and when males with FXS evidence atypical ANS function from infancy through early childhood, and how trajectories of ANS function across infancy and early childhood predict ASD and anxiety symptom severity later in development. Methods: Participants included 73 males with FXS and 79 age-matched typically developing (TD) males. Baseline heart activity was recorded at multiple assessments between 3 and 83 months of age, resulting in 372 observations. General arousal and parasympathetic activity were indexed via interbeat interval (IBI) and respiratory sinus arrhythmia (RSA), respectively. ASD and anxiety symptoms were assessed at 36 months of age or later in a subgroup of participants (FXS n = 28; TD n = 25). Results: Males with FXS exhibited atypical patterns of developmental change in ANS function across infancy and early childhood. As a result, ANS dysfunction became progressively more discrepant across time, with the FXS group exhibiting significantly shorter IBI and lower RSA by 29 and 24 months of age, respectively. Shorter IBI at 24 months and a flatter IBI slope across development predicted elevated anxiety symptoms, but not ASD symptoms, later in childhood in both FXS and TD males. Reduced RSA at 24 months predicted elevated ASD symptoms, but not anxiety symptoms, in both groups. Developmental change in RSA across early development did not predict later anxiety or ASD symptoms. Conclusion: This is the first longitudinal study to examine the "hyperarousal hypothesis" in infants and young children with FXS. Findings suggest that hyperarousal (i.e., shorter IBI, lower RSA) is evident in males with FXS by 24–29 months of age. Interestingly, unique aspects of early ANS function differentially relate to later ASD and anxiety symptoms. General arousal, indexed by shorter IBI that becomes progressively more discrepant from TD controls, predicts later anxiety symptoms. In contrast, parasympathetic-related factors, indexed by lower levels of RSA, predict ASD symptoms. These findings support the "hyperarousal hypothesis" in FXS, in that ANS dysfunction evident early in development predicts later-emerging symptoms of ASD and anxiety. This study also have important implications for the development of targeted treatments and interventions that could potentially mitigate the long-term effects of hyperarousal in FXS. [ABSTRACT FROM AUTHOR]