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

PURPOSE: Pragmatic language difficulties have been documented as part of the FMR1 premutation phenotype, yet the interplay between these features in mothers and the language outcomes of their children with fragile X syndrome is unknown. This study aimed to determine whether pragmatic language difficulties in mothers with the FMR1 premutation are related to the language development of their children. METHOD: Twenty-seven mothers with the FMR1 premutation and their adolescent/young adult sons with fragile X syndrome participated. Maternal pragmatic language violations were rated from conversational samples using the Pragmatic Rating Scale (Landa et al., 1992). Children completed standardized assessments of vocabulary, syntax, and reading. RESULTS: Maternal pragmatic language difficulties were significantly associated with poorer child receptive vocabulary and expressive syntax skills, with medium effect sizes. CONCLUSIONS: This work contributes to knowledge of the FMR1 premutation phenotype and its consequences at the family level, with the goal of identifying modifiable aspects of the 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

Lunar navigation study, sections 1 through 7 Final report, Jun. 1964 - May 1965

Lunar navigation analysis using passive nongyro, inertial navigation, and radio frequency technolog

Lunar navigation study, summary volume Final report, Jun. 1964 - May 1965

Lunar surface navigation and guidance study to implement lunar surface vehicle exploration mission

Attention/Deficit Hyperactivity Disorder in Adolescent and Young Adult Males With Fragile X Syndrome

This study characterized the rates of 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

Lunar navigation study, sections 8 through 10 and appendices Final report, Jun. 1964 - May 1965

Component capabilities and requirements for lunar navigation concept

Curvilinear Association Between Language Disfluency and FMR1 CGG Repeat Size Across the Normal, Intermediate, and Premutation Range

Historically, investigations of FMR1 have focused almost exclusively on the clinical effects of CGG expansion within the categories of the premutation (55–200 CGG repeats) and fragile X syndrome (\u3e200 CGG repeats). However, emerging evidence suggests that CGG-dependent phenotypes may occur across allele sizes traditionally considered within the “normal” range. This study adopted an individual-differences approach to determine the association between language production ability and CGG repeat length across the full range of normal, intermediate, and premutation alleles. Participants included 61 adult women with CGG repeats within the premutation (n = 37), intermediate (i.e., 41–54 repeats; n = 2), or normal (i.e., 6–40 repeats; n = 22) ranges. All participants were the biological mothers of a child with a developmental disorder, to control for the potential effects of parenting stress. Language samples were collected and the frequency of language disfluencies (i.e., interruptions in the flow of speech) served as an index of language production skills. Verbal inhibition skills, measured with the Hayling Sentence Completion Test, were also measured and examined as a correlate of language disfluency, consistent with theoretical work linking language disfluency with inhibitory deficits (i.e., the Inhibition Deficit Hypothesis). Blood samples were collected to determine FMR1 CGG repeat size. A general linear model tested CGG repeat size of the larger allele (allele-2) as the primary predictor of language disfluency, covarying for education level, IQ, age, and CGG repeats on the other allele. A robust curvilinear association between CGG length and language disfluency was detected, where low-normal (∼ \u3c25 \u3erepeats) and mid-premutation alleles (∼90–110 repeats) were linked with higher rates of disfluency. Disfluency was not associated with inhibition deficits, which challenges prior theoretical work and suggests that a primary language deficit could account for elevated language disfluency in FMR1-associated conditions. Findings suggest CGG-dependent variation in language production ability, which was evident across individuals with and without CGG expansions on FMR1

Building the Future Therapies for Down Syndrome: The Third International Conference of the T21 Research Society

Research focused on Down syndrome has increased in the last several years to advance understanding of the consequences of trisomy 21 (T21) on molecular and cellular processes and, ultimately, on individuals with Down syndrome. The Trisomy 21 Research Society (T21RS) is the premier scientific organization for researchers and clinicians studying Down syndrome. The Third International Conference of T21RS, held June 6–9, 2019, in Barcelona, Spain, brought together 429 scientists, families, and industry representatives to share the latest discoveries on underlying cellular and molecular mechanisms of T21, define cognitive and behavioral challenges and better understand comorbidities associated with Down syndrome, including Alzheimer’s disease and leukemia. Presentation of cutting-edge results in neuroscience, neurology, model systems, psychology, cancer, biomarkers and molecular and phar­ma­cological therapeutic approaches demonstrate the compelling interest and continuing advancement in all aspects of understanding and ameliorating conditions associated with T21

Contributions of phonological and verbal working memory to language development in adolescents with fragile X syndrome

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. Although language delays are frequently observed in FXS, neither the longitudinal course of language development nor its cognitive predictors are well understood. The present study investigated whether phonological and working memory skills are predictive of growth in vocabulary and syntax in individuals with FXS during adolescence. Forty-four individuals with FXS (mean age = 12.61 years) completed assessments of phonological memory (nonword repetition and forward digit recall), verbal working memory (backward digit recall), vocabulary, syntax, and nonverbal cognition. Vocabulary and syntax skills were reassessed at a 2-year follow-up. In a series of analyses that controlled for nonverbal cognitive ability and severity of autism symptoms, the relative contributions of phonological and working memory to language change over time were investigated. These relationships were examined separately for boys and girls. In boys with FXS, phonological memory significantly predicted gains in vocabulary and syntax skills. Further, verbal working memory was uniquely associated with vocabulary gains among boys. In girls with FXS, phonological and working memory skills showed no relationship with language change across the 2-year time period. Our findings indicate that, for adolescent boys with FXS, acquisition of vocabulary and syntax may be constrained by the ability to maintain and manipulate phonological representations online. Implications for the identification and treatment of language disorders in this population are discussed. The present study is the first to identify specific cognitive mechanisms contributing to language growth over time in individuals with FXS

Early mortality and primary causes of death in mothers of children with ID or ASD: a retrospective cohort study

INTRODUCTION: Mothers of children with intellectual disability or autism spectrum disorder (ASD) have poorer health than other mothers. Yet no research has explored whether this poorer health is reflected in mortality rates or whether certain causes of death are more likely. We aimed to calculate the hazard ratios for death and for the primary causes of death in mothers of children with intellectual disability or ASD compared to other mothers. METHODS: The study population comprised all mothers of live-born children in Western Australia from 1983-2005. We accessed state-wide databases which enabled us to link socio-demographic details, birth dates, diagnoses of intellectual disability or ASD in the children and dates and causes of death for all mothers who had died prior to 2011. Using Cox Regression with death by any cause and death by each of the three primary causes as the event of interest, we calculated hazard ratios for death for mothers of children intellectual disability or ASD compared to other mothers. RESULTS AND DISCUSSION: During the study period, mothers of children with intellectual disability or ASD had more than twice the risk of death. Mothers of children with intellectual disability were 40% more likely to die of cancer; 150% more likely to die of cardiovascular disease and nearly 200% more likely to die from misadventure than other mothers. Due to small numbers, only hazard ratios for cancer were calculated for mothers of children with ASD. These mothers were about 50% more likely to die from cancer than other mothers. Possible causes and implications of our results are discussed. CONCLUSION: Similar studies, pooling data from registries elsewhere, would improve our understanding of factors increasing the mortality of mothers of children with intellectual disability or ASD. This would allow the implementation of informed services and interventions to improve these mothers' longevity

Building the Future Therapies for Down Syndrome:The Third International Conference of the T21 Research Society

Research focused on Down syndrome has increased in the last several years to advance understanding of the consequences of trisomy 21 (T21) on molecular and cellular processes and, ultimately, on individuals with Down syndrome. The Trisomy 21 Research Society (T21RS) is the premier scientific organization for researchers and clinicians studying Down syndrome. The Third International Conference of T21RS, held June 6-9, 2019, in Barcelona, Spain, brought together 429 scientists, families, and industry representatives to share the latest discoveries on underlying cellular and molecular mechanisms of T21, define cognitive and behavioral challenges and better understand comorbidities associated with Down syndrome, including Alzheimer's disease and leukemia. Presentation of cutting-edge results in neuroscience, neurology, model systems, psychology, cancer, biomarkers and molecular and phar-ma-cological therapeutic approaches demonstrate the compelling interest and continuing advancement in all aspects of understanding and ameliorating conditions associated with T21