Word retrieval difficulty in adult females with the FMR1 premutation: Changes over time and across contexts.

Individuals with a premutation of the fragile X mental retardation (FMR1) gene are at risk for a variety of psychological, physical, and cognitive issues, including difficulty with word retrieval. The present study examined three indicators of word retrieval difficulty; reduced productivity, reduced lexical diversity, and increased errors in word retrieval in a group of 38 female premutation carriers during standard-length speech samples collected over a period of eight years. Our results revealed that as women aged, they produced fewer words, produced fewer different words, and had greater word retrieval errors. In addition, the rate of word retrieval errors was highly correlated between two speaking contexts, indicating that this difficulty was pervasive and not solely the result of speaking in monologue. Our results suggest that subtle areas of cognitive decline emerge at a much earlier age among female premutation carriers than would be expected during healthy aging.

Mothers' perspectives on challenging behaviours in their children with fragile X syndrome.

BACKGROUND: Individuals with intellectual and developmental disabilities are more likely to engage in problem behaviours than peers with typical development. The purpose of this study was to provide descriptive and qualitative information about problem behaviours in children with fragile X syndrome (FXS) and how families respond to these behaviours. METHOD: We examined interview responses from 53 mothers of 9-year-old children with FXS. RESULTS: Defiance, tantrums, inattention, stereotypy, and aggression were the most frequently reported problem behaviours of children with FXS. Stereotypy, physical aggression, self-injury, and elopement were reported more often by mothers of children with dual diagnoses of FXS and autism than by mothers of children with a single diagnosis of FXS. CONCLUSIONS: Results indicated that for many families, by 9 years of age, problem behaviours led to frustration and altered family activities.

Language dysfluencies in females with the FMR1 premutation.

Recent evidence suggests that there are age-related neurocognitive implications for fragile X premutation carriers, including deficits in executive function, and that such deficits are more common in male than female premutation carriers. The purpose of the current study is to examine one aspect of executive function, language dysfluencies, in a group of 193 women with the premutation, and to contrast them with a comparison group (mothers of children with autism spectrum disorders). Our results demonstrate a linguistic profile in the female premutation carriers characterized by dysfluencies associated with deficits in organization and planning, with a clear impact of age. The comparison group, matched on both age and education level, did not demonstrate the age effect. Our results suggest dysfluencies could be an early indicator of cognitive aging in some female premutation carriers, and could be used to target early intervention.

Transactional relationships between maternal requesting and responsivity, adolescent compliance, and task demands in fragile X syndrome.

BACKGROUND: Males with fragile X syndrome (FXS) may have difficulty with social communication and language in addition to behavioral concerns such as noncompliance to maternal requests. Mothers vary in how they pose requests to their children, and contextual demands may also be a factor in compliance. This study examined the relationships between maternal requesting behaviors, maternal responsivity, child compliance, and task demands in adolescent males with FXS. METHODS: 35 mother-son dyads completed three interactive tasks during in-home visits (puzzle, iPad games, snack). The adolescents also completed assessments of language and autism symptoms. The three interactive tasks were video-recorded, and behavior-by-behavior coding and transcription was completed. RESULTS: Comparing between tasks, mothers requested a behavior most often during the snack task and used a higher proportion of indirect requests during the iPad task. Adolescents were largely compliant across tasks, with average compliance equal to 70%. Adolescent compliance was predicted by maternal request frequency such that mothers who used more requests had adolescent sons who were less compliant. Maternal responsivity was higher for mothers of adolescents with FXS-only compared to those with FXS and high autism symptoms. CONCLUSIONS AND IMPLICATIONS: Task demands may have influenced maternal requesting, which in turn may have impacted adolescent compliance. Compliance with requests is important for both social and educational aspects of life, and further study of requesting and compliance in FXS is needed to identify effective teaching and behavioral intervention methods.

Sex differences in infant vocalization and the origin of language.

Seeking to discern the earliest sex differences in language-related activities, our focus is vocal activity in the first two years of life, following up on recent research that unexpectedly showed boys produced significantly more speech-like vocalizations (protophones) than girls during the first year of life.We now bring a much larger body of data to bear on the comparison of early sex differences in vocalization, data based on automated analysis of all-day recordings of infants in their homes. The new evidence, like that of the prior study, also suggests boys produce more protophones than girls in the first year and offers additional basis for informed speculation about biological reasons for these differences. More broadly, the work offers a basis for informed speculations about foundations of language that we propose to have evolved in our distant hominin ancestors, foundations also required in early vocal development of modern human infants.

Effectiveness of Responsivity Intervention Strategies on Prelinguistic and Language Outcomes for Children with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis of Group and Single Case Studies.

We conducted a systematic review to identify randomized controlled trials (RCTs) and single case research design (SCRD) studies of children with autism spectrum disorder that evaluate the effectiveness of responsivity intervention techniques for improving prelinguistic and/or language outcomes. Mean effect sizes were moderate and large for RCTs (33 studies; g = 0.36, 95% CI [0.21, 0.51]) and SCRD (34 studies; between-case standardized mean difference = 1.20, 95% CI [0.87, 1.54]) studies, respectively. Visual analysis (37 studies) revealed strong evidence of a functional relation for 45% of the opportunities and no evidence for 53%. Analyses of moderator effects and study quality are presented. Findings provide support for responsivity intervention strategies with more robust support for context-bound outcomes than more generalized outcomes.

Maternal well-being and family adaptation during COVID-19 in fragile X syndrome.

Mothers of children with fragile X syndrome are at increased risk of experiencing anxiety and depression due to potential genetic risk and to stress associated with parenting a child with significant behavioral, emotional, and educational support needs. During the initial shutdown and subsequent restrictions of the COVID-19 pandemic, mothers of children with fragile X reported experiencing elevated levels of anxiety and depression relative to their usual levels of well-being. Many indicated that the negative consequences of exposure to COVID-19 and related stressors, as well as the impacts of the pandemic on their family, directly affected their anxiety and depression. Mothers reported on specific sources of distress as well as potential sources of resilience and positive adaptation that occurred during the first year of the COVID-19 pandemic.

Change in Behavior Problems from Childhood Through Adolescence for Children with Fragile X Syndrome.

In this study, we examined trajectories of specific domains of behavior problems (i.e., attention problems, depression/anxiety, and aggressive behavior) from age 6 to 18 in a sample of 55 children with fragile X syndrome. We also examined autism status and early parenting as predictors of subsequent behavioral trajectories. We found that attention problems and aggressive behavior declined steadily from childhood through adolescence whereas anxious/depressed behavior demonstrated relative stability over the same period. Youth with highly flexible mothers displayed more optional trajectories of improvement in attention problems.

Descriptive analysis of seizures and comorbidities associated with fragile X syndrome.

BACKGROUND: Fragile X syndrome is characterized by a myriad of physical features, behavioral features, and medical problems. Commonly found behavioral features are hyperactivity, anxiety, socialization difficulties, and ASD. There is also a higher incidence than in the general population of strabismus, otitis media, and mitral valve prolapse. In addition, one of the most common medical problems associated with FXS is an increased risk of seizures. A subset of individuals carrying the full mutation of the FMR1 gene and diagnosed with fragile X syndrome (FXS) are reported to experience seizures, mostly during the first 10 years of their life span. METHODS: As part of a larger project to identify genetic variants that modify the risk of seizures, we collected clinical information from 49 carriers with FXS who experienced seizures and 46 without seizures. We compared seizure type and comorbid conditions based on the source of data as well as family history of seizures. RESULTS: We found that the concordance of seizure types observed by parents and medical specialists varied by type of seizure. The most common comorbid condition among those with seizures was autism spectrum disorder (47% per medical records vs. 33% per parent report compared with 19% among those without seizures per parent report); the frequency of other comorbid conditions did not differ among groups. We found a slightly higher frequency of family members who experienced seizures among the seizure group compared with the nonseizure group. CONCLUSION: This study confirms previously reported features of seizures in FXS, supports additional genetic factors, and highlights the importance of information sources, altogether contributing to a better understanding of seizures in FXS.

Examination of the ADOS-2 Expressive Language Score in Fragile X Syndrome.

The development of an expressive language score for people with autism based on the ADOS-2 was recently reported by Mazurek et al. (2019). The current study examined the construct validity of the ADOS-2 expressive language score (ELS) in a sample of adolescents with fragile X syndrome (n = 45, 10 girls), a neurodevelopmental disorder with high rates of autism symptomology. The ADOS-2 ELS showed strong convergent validity with multiple assessments of expressive language, receptive language, and nonverbal cognition. Divergent validity was demonstrated between the expressive language score and chronological age, symptoms of anxiety/depression, and rule-breaking behaviors. This expressive language score is a promising measure of expressive language ability that can be used in research when other language assessments are unavailable.

Rethinking Measurement Standards of Autism Symptomology in Adolescents with Fragile X Syndrome.

Accurate representation of autism spectrum disorder (ASD) in fragile X syndrome (FXS) is necessary for the field. We examined classifications of ASD using three approaches-Autism Diagnostic Observation Schedule (ADOS-2; Lord et al. 2012), Childhood Autism Rating Scale (CARS2-ST; Schopler et al. 2010), and Vineland Adaptive Behavior Scales (VABS-II; Sparrow et al. 2005)-in 45 adolescents with FXS. Maladaptive items from the VABS-II plus a maternal interview were matched with Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5; American Psychiatric Association 2013) criteria for ASD. Results indicated discrepant classifications. The ADOS-2 yielded the highest rate of comorbid autism (71%); CARS2-ST and VABS-II/DSM-5 yielded lower rates (38% and 42%, respectively). A singular measure of autism symptomology is insufficient to characterize autism in FXS.

Opportunities, barriers, and recommendations in down syndrome research.

BACKGROUND: Recent advances in medical care have increased life expectancy and improved the quality of life for people with Down syndrome (DS). These advances are the result of both pre-clinical and clinical research but much about DS is still poorly understood. In 2020, the NIH announced their plan to update their DS research plan and requested input from the scientific and advocacy community. OBJECTIVE: The National Down Syndrome Society (NDSS) and the LuMind IDSC Foundation worked together with scientific and medical experts to develop recommendations for the NIH research plan. METHODS: NDSS and LuMind IDSC assembled over 50 experts across multiple disciplines and organized them in eleven working groups focused on specific issues for people with DS. RESULTS: This review article summarizes the research gaps and recommendations that have the potential to improve the health and quality of life for people with DS within the next decade. CONCLUSIONS: This review highlights many of the scientific gaps that exist in DS research. Based on these gaps, a multidisciplinary group of DS experts has made recommendations to advance DS research. This paper may also aid policymakers and the DS community to build a comprehensive national DS research strategy.

Assessment of Language Abilities in Minority Adolescents and Young Adults With Autism Spectrum Disorder and Extensive Special Education Needs: A Pilot Study.

Purpose Little is known about the language abilities of adolescents and young adults with autism spectrum disorder (ASD) despite the importance of language in their other life outcomes. Even less is known about the language abilities of racial/ethnic minorities with ASD and extensive special education needs. These gaps limit our understanding of adolescents and young adults with ASD. Method A pilot study evaluated the efficacy of individualized age-referenced language assessment for minority adolescents and young adults with ASD in self-contained special education settings. Participants (n = 10) completed the Clinical Evaluation of Language Fundamentals-Third Edition, Test for Early Grammatical Impairment (TEGI), Columbia Mental Maturity Scale, and Wechsler Intelligence Scale for Children-Third Edition Digit Span. Results Clinical Evaluation of Language Fundamentals-Third Edition scores showed little variation, with most participants showing a floor effect. TEGI, Columbia Mental Maturity Scale, and Digit Span scores showed greater variation. Some participants had ceiling TEGI scores, and some had variable assessment profiles. Conclusion Assessment was sensitive to variability across some measures. The pilot study outcomes support the feasibility and potential informativeness of additional investigation of conventional language assessments and change over time.

Child Challenging Behavior Influences Maternal Mental Health and Relationship Quality Over Time in Fragile X Syndrome.

Parenting children with neurodevelopmental disabilities is often challenging. Biological mothers of children with Fragile X Syndrome (FXS) may be susceptible to increased risk of mental health problems. This study examined the longitudinal relationships between maternal mental health, child challenging behaviors, and mother-child relationship quality in children and adolescents with FXS. Fifty-five mother-child dyads were followed from childhood into adolescence. The findings suggest that child challenging behaviors, maternal mental health, and mother-child relationship quality were stable during that period. Additionally, elevated levels of child challenging behaviors negatively impacted maternal mental health. Finally, child challenging behaviors, in combination with maternal mental health, influenced mother-child relationship quality. Clinical implications are discussed.

Developmental Trajectory of Communication Repair in Children with Fragile X Syndrome.

BACKGROUND & AIMS: The development of communicative competence requires both language and social skills. The ability to repair following a communication breakdown is critical for continued conversational interchange and to ensure comprehension of bids for communication. Repair demonstrates adequate language and social skills. Children with Fragile X Syndrome (FXS) have difficulty with language development and social skills, which may result in delays or deficits in repair. Repair may be additionally impaired in children with FXS and co-morbid autism. This study examined the development of repair in children with FXS from toddlerhood into middle childhood. METHODS: Fifty-five children with FXS and their biological mothers participated. Data were collected during in-home visits approximately every 18 months. Videotaped mother-child interactions were collected, as well as standardized assessments of language, social skills, and autism symptomology. RESULTS: Children with FXS acquired the ability to repair at 90% mastery by three-and-a-half years of age. Multilevel logistic regressions predicting probability of repair indicated marginally significant effects of mean length of utterance and number of different words, and significant effects of global social skills and autism symptomology. Effect sizes were small to moderate. CONCLUSIONS: Ability to repair was measured in a naturalistic setting, which allowed children with FXS to utilize repairs in their daily interactions. Although children with FXS may have delayed development of repair relative to typically developing expectations, in general they nonetheless catch up and demonstrate a robust ability to repair by three-and-a-half years of age. However, this study provides evidence that individual differences in language and social skills may influence ability to repair in children with FXS. Finally, the relationship between autism symptoms and repair remains unclear, necessitating further exploration. IMPLICATIONS: Given the noted delay in repair in young children with FXS, clinicians working with this population should target development of this skill as early as possible to maximize successful social interactions. This may be particularly necessary for children with FXS and co-morbid autism.

Language Development From Early Childhood to Adolescence in Youths With Fragile X Syndrome.

Purpose The aim of this study was to investigate language growth in individuals with fragile X syndrome (FXS) from early childhood to adolescence and the influence of maternal responsivity on language growth. Method We conducted a longitudinal analysis of language development in 55 youths (44 males, 11 females) with FXS. Data collection spanned the ages of 11-216 months. We measured expressive and receptive vocabulary with standardized tests. The number of different words and mean length of utterance were obtained from language sample analyses of mother-child interactions. We also measured maternal comments (responsivity indicator) produced during the language samples and child nonverbal IQ. Results Growth models indicated that rates of number of different words and receptive vocabulary were related to maternal commenting. Mean length of utterance did not change significantly over time. Expressive vocabulary measured with a standardized test grew, but the growth was not related to maternal commenting. Nonverbal IQ was related to all language outcomes at age of 10 years and to changes over time in vocabulary. Visual analysis indicated that the highest scores on standardized tests were produced by girls; however, measures derived from language sample analyses appeared similar for boys and girls. Language models for boys only were similar to the total sample models with lower scores at age of 10 years for some outcomes. Conclusion Results of persistent language impairments for most youths with FXS suggest the need for continued, focused interventions aimed at improved language productions in addition to a responsive environment. Supplemental Material https://doi.org/10.23641/asha.13022825.

Supporting family adaptation to presymptomatic and "untreatable" conditions in an era of expanded newborn screening.

OBJECTIVE: As technology advances, newborn screening will be possible for conditions not screened today. With an expansion of screening, strategies will be needed to support family adaptation to unexpected and possibly uncertain genetic information provided shortly after birth. METHOD: Although candidate conditions for expanded newborn screening will typically be associated with increased morbidity or mortality, for most there is no proven medical treatment that must be implemented quickly. Many will have clinical features that gradually emerge and for which the severity of impact is not predictable. Parents will seek guidance on information, support, and treatment possibilities. This article summarizes issues evoked by expanded newborn screening and suggests strategies for supporting families of identified children. RESULTS: We propose four components necessary to support family adaptation to pre-symptomatic and "untreatable" conditions in an era of expanded newborn screening: (1) accurate and understandable information; (2) formal and informal support; (3) active surveillance; and (4) general and targeted interventions. We argue that no condition is "untreatable" and that a well-designed program of prevention and support has the potential to maximize benefit and minimize harm. CONCLUSIONS: Pediatric psychologists can play important roles in an era of expanded newborn screening by helping families understand genetic information, make informed decisions about genetic testing, and cope with the potential psychosocial consequences of genetic information.

Early Predictors of Later Expressive Language in Boys With Fragile X Syndrome.

The predictive ability of early consonant inventory and intentional communication on later expressive language was examined in 36 boys with fragile X syndrome (FXS). Autism symptom severity was included as a potential moderator. Participants were visited in their homes twice over a 6-year period, and mother-child interactions were videotaped, coded, and transcribed behavior by behavior. Consonant inventory and concurrent autism symptom severity were predictive of later number of different words, as was the interaction between the two. Intentional communication was not predictive of number of different words. These findings provide additional specific evidence for differences in foundational language abilities associated with autism symptom severity in boys with FXS. Clinical implications are discussed.

A randomized trial of longitudinal effects of low-intensity responsivity education/prelinguistic milieu teaching.

PURPOSE: To evaluate the longitudinal effects of a 6-month course of responsivity education (RE)/prelinguistic milieu teaching (PMT) for young children with developmental delay. METHOD: Fifty-one children, age 24-33 months, with fewer than 10 expressive words were randomly assigned to early-treatment/no-treatment groups. All treatment was added as a supplement to services that the children received in the community. Follow-up data were collected 6 and 12 months after the conclusion of the initial 6-month treatment/no-treatment conditions. RESULTS: No effects of this treatment were detected 6 or 12 months after the conclusion of the initial treatment condition. CONCLUSIONS: M. E. Fey et al. (2006) reported that 6 months of RE/PMT led to a significant treatment effect in the use of intentional communication in 1 of 2 communication sampling contexts. This finding, combined with evidence from other studies, suggests that RE/PMT may be applied clinically at low intensity with the expectation of medium-sized effects on children's rate of intentional communication acts over the short term. The results of the present study, however, provide no evidence for the anticipated longer term benefits of this intervention. Further investigation of the approach at higher intensity levels and for longer periods of time is warranted.

Parenting of children with Down syndrome compared to fragile X syndrome.

Children with Down syndrome (DS) and fragile X syndrome (FXS) struggle with language development. Parenting variables, such as responsiveness to children's communication attempts (Maternal Responsivity), and techniques used to support and teach appropriate behavior (Behavior Management) are known to have a significant impact on early child development. We examined these two aspects of parenting style via coded, videotaped parent-child interactions in two groups of participants matched on child age (2-5 years) and child expressive language level: mothers of children with DS and mothers of children with FXS. The mothers differed in their use of gestures and redirecting the child's attention. Overall, mothers in both groups of children appeared to adapt appropriately to their children's developmental needs.