Cognitive training for children and adolescents with fragile X syndrome: a randomized controlled trial of Cogmed.

BACKGROUND: Individuals with fragile X syndrome (FXS) typically demonstrate profound executive function (EF) deficits that interfere with learning, socialization, and emotion regulation. We completed the first large, non-pharmacological controlled trial for FXS, designed to evaluate the efficacy of Cogmed, a computer/tablet-based working memory (WM) training program. METHODS: The study was a randomized, blinded, parallel two-arm controlled trial in 100 children and adolescents with FXS (63 male, 37 female; 15.28 ± 3.36 yrs.). Participants were randomized equally to adaptive (difficulty level adjusted to performance) or non-adaptive (control) Cogmed training. Participants were assessed at home using objective measures of WM (primary outcome) and EF at baseline, following 20-25 caregiver-supported sessions over 5-6 weeks, and at follow-up 3 months after cessation of training. Parents and teachers provided ratings of WM, attention, and EF. RESULTS: The WM composite and selective domains of EF (distractibility, cognitive flexibility), as well as parent- and teacher-reported attention and EF, significantly improved across the full study sample, with many changes maintained at follow-up. However, comparisons of improvement between adaptive and non-adaptive control conditions did not differ, showing that progressively challenging the WM system by expanding span length did not provide added benefit overall. CONCLUSIONS: Further experimental comparisons are needed before Cogmed working memory training can be considered empirically validated for children with FXS, forming the basis of treatment recommendation. However, given that prior studies show no significant changes on these measures in FXS without treatment, that improvements were maintained for 3 months, and that blinded teachers reported improvements in the classroom, the modest benefits seen in both adaptive and non-adaptive groups overall are unlikely to be attributable to placebo or practice effects alone. Future analyses examining inter-individual differences (e.g., baseline capacity, training efficiency, co-morbidity, training environment, characteristics of training aide) may help to link this intervention to outcomes and potential transfer effects. TRIAL REGISTRATION: US National Institutes of Health (ClinicalTrials.gov), NCT02747394 .

Mobile technology use and skills among individuals with fragile X syndrome: implications for healthcare decision making.

BACKGROUND: Little is known about how individuals with fragile X syndrome (FXS) and their families use technology in daily life and what skills individuals with FXS can perform when using mobile technologies. METHODS: Using a mixed-methods design, including an online survey of parents (n = 198) and a skills assessment of individuals with FXS (n = 6), we examined the experiences and abilities of individuals with FXS for engaging with mobile technology. RESULTS: Parents reported that individuals with FXS often used technology in their daily lives, with variations based on age of child, sex, autism status, depression, and overall ability. Parents frequently sought and shared FXS-related information online. Assessment data revealed that individuals with FXS demonstrated proficiency in interacting with technology. CONCLUSIONS: Mobile technology is a tool that can be used in FXS to build skills and increase independence rather than simply for recreational purposes. Implications for using mobile technology to enhance healthcare decision making are discussed.

Reading in Children With Fragile X Syndrome: Phonological Awareness and Feasibility of Intervention.

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.

Inferential language use by school-aged boys with fragile X syndrome: Effects of a parent-implemented spoken language intervention.

This study examined the impact of a distance-delivered parent-implemented narrative language intervention on the use of inferential language during shared storytelling by school-aged boys with fragile X syndrome, an inherited neurodevelopmental disorder. Nineteen school-aged boys with FXS and their biological mothers participated. Dyads were randomly assigned to an intervention or a treatment-as-usual comparison group. Transcripts from all pre- and post-intervention sessions were coded for child use of prompted and spontaneous inferential language coded into various categories. Children in the intervention group used more utterances that contained inferential language than the comparison group at post-intervention. Furthermore, children in the intervention group used more prompted inferential language than the comparison group at post-intervention, but there were no differences between the groups in their spontaneous use of inferential language. Additionally, children in the intervention group demonstrated increases from pre- to post-intervention in their use of most categories of inferential language. This study provides initial support for the utility of a parent-implemented language intervention for increasing the use of inferential language by school aged boys with FXS, but also suggests the need for additional treatment to encourage spontaneous use.

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.

Distance delivery of a spoken language intervention for school-aged and adolescent boys with fragile X syndrome.

A small randomized group design (N = 20) was used to examine a parent-implemented intervention designed to improve the spoken language skills of school-aged and adolescent boys with FXS, the leading cause of inherited intellectual disability. The intervention was implemented by speech-language pathologists who used distance video-teleconferencing to deliver the intervention. The intervention taught mothers to use a set of language facilitation strategies while interacting with their children in the context of shared story-telling. Treatment group mothers significantly improved their use of the targeted intervention strategies. Children in the treatment group increased the duration of engagement in the shared story-telling activity as well as use of utterances that maintained the topic of the story. Children also showed increases in lexical diversity, but not in grammatical complexity.

Assistive technology to promote occupation and reduce mouthing by three boys with fragile X syndrome.

OBJECTIVES: To extend the use of assistive technology (AT) for promoting a new adaptive response and to reduce hand mouthing, by three boys with fragile X syndrome. To monitor the effects of the intervention program on the positive mood. To carry out a three month follow-up phases. To conduct a social validation assessment involving 30 parents of children who presented multiple disabilities as raters. METHODS: The study was implemented according to an ABAB experimental design, where A represented baseline phases (technology available but inactive) and B represented intervention phases (the technology ensured 7 s of positive stimulation). RESULTS: All participants improved and consolidated their performance. Parents involved in the social validation assessment rated positively the use of such technology. CONCLUSION: AT-based program was useful, affordable, and effective for enhancing constructive engagement, self-determination, and for improving quality of life by children with fragile X syndrome and severe to profound developmental disabilities.

Three Faces of Fragile X.

Fragile X syndrome (FXS) is the first of 3 syndromes identified as a health condition related to fragile X mental retardation (FMR1) gene dysfunction. The other 2 syndromes are fragile X-associated primary ovarian insufficiency syndrome (FXPOI) and fragile X-associated tremor/ataxia syndrome (FXTAS), which together are referred to as fragile X-associated disorders (FXDs). Collectively, this group comprises the 3 faces of fragile X. Even though the 3 conditions share a common genetic defect, each one is a separate health condition that results in a variety of body function impairments such as motor delay, musculoskeletal issues related to low muscle tone, coordination limitations, ataxia, tremor, undefined muscle aches and pains, and, for FXTAS, a late-onset neurodegeneration. Although each FXD condition may benefit from physical therapy intervention, available evidence as to the efficacy of intervention appropriate to FXDs is lacking. This perspective article will discuss the genetic basis of FMR1 gene dysfunction and describe health conditions related to this mutation, which have a range of expressions within a family. Physical therapy concerns and possible assessment and intervention strategies will be introduced. Understanding the intergenerational effect of the FMR1 mutation with potential life-span expression is a key component to identifying and treating the health conditions related to this specific genetic condition.

The effects of intertrial interval and instructional format on skill acquisition and maintenance for children with autism spectrum disorders.

We replicated and extended the study by Koegel, Dunlap, and Dyer (1980) by examining the effects of 3 intertrial-interval (ITI) durations on skill acquisition in 2 children with autism spectrum disorders. Specifically, we compared the effect of short (2 s), progressive (2 s to 20 s), and long (20 s) ITIs on participants' mastery of tacts or intraverbals presented in massed-trial and varied-trial instructional formats. We also measured (a) stereotypic and problem behavior during the ITI, (b) maintenance of skills, and (c) responding to novel adults and settings. Results showed that short ITIs in a varied-trial format produced the most efficient acquisition of skills; however, most ITI durations produced more efficient skill acquisition in a varied format compared to a massed format. The trial format and ITI duration associated with the lowest levels of stereotypic and problem behavior during the ITI and responding during maintenance and novel adult and setting probes differed across participants.

A Spoken-Language Intervention for School-Aged Boys With Fragile X Syndrome.

Using a single case design, a parent-mediated spoken-language intervention was delivered to three mothers and their school-aged sons with fragile X syndrome, the leading inherited cause of intellectual disability. The intervention was embedded in the context of shared storytelling using wordless picture books and targeted three empirically derived language-support strategies. All sessions were implemented through distance videoteleconferencing. Parent education sessions were followed by 12 weekly clinician coaching and feedback sessions. Data were collected weekly during independent homework and clinician observation sessions. Relative to baseline, mothers increased their use of targeted strategies, and dyads increased the frequency and duration of story-related talking. Generalized effects of the intervention on lexical diversity and grammatical complexity were observed. Implications for practice are discussed.

Functional analysis and treatment of problem behavior exhibited by children with fragile X syndrome.

The efficacy of function-based interventions for the treatment of severe problem behavior exhibited by individuals with intellectual and developmental disabilities (IDD) is well established. However, few studies have reported on behavioral interventions in fragile X syndrome (FXS) specifically. The present study is a consecutive case-series analysis that reports on functional analysis and treatment of problem behavior of nine children with FXS. Assessment findings were consistent with previous research indicating that among individuals with FXS, problem behavior is more commonly maintained by escape from demands and access to tangible items, relative to the broader population of individuals with IDD. Functional analysis-based behavioral interventions resulted in a mean reduction in problem behavior of 95.2% across the nine participants. Additionally, generalization of treatment effects from controlled clinical settings to home, school, and community was demonstrated. The current findings suggest that function-based behavioral interventions shown to be effective with the broader population of individuals with IDD are also effective for individuals with FXS. Our results in combination with those of previous studies describing functional analysis outcomes provide additional evidence for a unique functional behavioral phenotype for severe problem behavior in individuals with FXS. Implications of study findings for early intervention and prevention of problem behavior in children with FXS are discussed.

Uncovering the evidence for behavioral interventions with individuals with fragile X syndrome: a systematic review.

Fragile X syndrome (FXS) is associated with a wide range of cognitive, emotional, and behavioral difficulties. Although there is considerable research on the behavioral phenotype of FXS, few empirical studies of behavioral interventions with this population have been identified. Through a hand search of 34 behavioral journals, we examined the evidence base for behavioral interventions with individuals with FXS and in light of the current state of knowledge regarding the FXS behavioral phenotype. Systematic review procedures were used to identify behavioral intervention studies that included at least one participant with FXS, extract and summarize the data on several relevant dimensions, and rate the methodological quality of the studies. Results revealed 31 intervention studies with a small number of participants with FXS. Overall, results suggest a behavioral approach to intervention with individuals with FXS shows promise. Future research focused on individuals with FXS will be necessary to continue to examine differences in response to intervention and interventions that specifically address phenotypic characteristics.

Providing a parent-implemented language intervention to a young male with fragile X syndrome: brief report.

PURPOSE: Although fragile X syndrome (FXS) is the leading inherited cause of intellectual disability, there are no published intervention studies focused on improving communication and language outcomes for affected children. The current study utilized a collaborative coaching approach incorporating strategies from speech-language pathology and applied behavior analysis to examine the efficacy of a naturalistic parent-implemented language intervention for a young boy with FXS. METHODS: The mother was taught the language and behavioral support strategies and submitted weekly video recordings of a caregiving routine. Written feedback was provided. RESULTS: Results indicated moderate increases in maternal use of targeted language support strategies and variable performance in maternal use of behavior support strategies. Child use of appropriate requests increased while challenging behaviors decreased. CONCLUSIONS: This collaborative approach model should be used to guide future larger scale replications and develop new intervention models.

A comparative study of educational provision for children with neurogenetic syndromes: parent and teacher survey.

BACKGROUND: A number of neurogenetic syndromes have a high association with special educational needs including fragile X syndrome (FXS), Prader-Willi syndrome (PWS), Williams syndrome (WS) and Velo-Cardio-Facial syndrome (VCFS). There is a paucity of research on educational provision for children affected by these syndromes. METHOD: Parents (n = 381) and teachers (n = 204) of school-aged children with one of the four syndromes in the UK and Ireland were surveyed in a range of areas concerning the child's educational provision. Areas surveyed included school placement, views on the needs of children with the syndromes, desired changes to current provision and perceived teacher knowledge. RESULTS: School placement in mainstream settings decreased with age in all of the syndromes. Males with the syndromes were more likely to be in specialised educational settings with the exception of WS. Teachers reported limited input on initial or subsequent training for all of the syndromes. The majority of teachers did not view the needs of children with syndromes as different from other children with intellectual disability (ID) although there were significant differences between the syndromes. Changes deemed necessary to provision by parents and teachers differed between the syndromes indicating the existence of perceptions of syndrome specific needs. The lowest perceived level of teacher knowledge was in the VCFS group. CONCLUSION: The majority of teachers of children with neurogenetic syndromes report limited knowledge of the syndromes, but also a lack of belief that the children's needs are different from the majority of children with ID. Differences between the syndromes in some areas of provision suggest that a child's syndrome does impact on educational provision in some areas.

Technological supports to promote choice opportunities by two children with fragile X syndrome and severe to profound developmental disabilities.

This study was aimed at assessing whether technological supports (i.e. optic sensors such as photocells) were successful enabling two boys with fragile X syndrome and severe to profound developmental disabilities to perform occupation and choice opportunities. A second goal of the study was to reduce stereotyped behaviours (i.e. hand mouthing and eye poking) exhibited by the participants. Finally, the third purpose of the study was to verify the rehabilitative effects of the intervention program on the indices of happiness of the participants. The study has been conducted according to a non-concurrent multiple baseline design across participants followed by intervention and cross over phases, where the associations between behavioural responses and environmental consequences were systematically inverted. Moreover, a maintenance phase was assessed. The results demonstrated that the technology is useful to facilitate employment and opportunities of choice, showing a growth of the indices of happiness and a decrease of stereotyped behaviours, from both participants involved. Clinical, practical and psychological implications of the findings are discussed.

Effect of sustained maternal responsivity on later vocabulary development in children with fragile X syndrome.

PURPOSE: This research explored whether sustained maternal responsivity (a parent­child interaction style characterized by warmth, nurturance, and stability as well as specific behaviors, such as contingent positive responses to child initiations) was a significant variable predicting vocabulary development of children with fragile X syndrome through age 9 years. METHOD: Fifty-five mother­child dyads were followed longitudinally when children were between 2 and 10 years of age. Measures of maternal responsivity and child vocabulary were obtained at regular intervals starting at age 2.9 years. Sustained responsivity was indicated by the average responsivity measured over Observations 2­5. Responsivity at the 1st time period, autism symptoms, and cognitive development were used as control variables. RESULTS: After controlling for development and autism symptoms, the authors found significant effects for sustained responsivity on receptive vocabulary, expressive vocabulary, and the rate of different words children produced through age 9. CONCLUSIONS: Maternal responsivity, which is typically a variable of interest during early childhood, continues to be a significant variable, predicting vocabulary development through the middle childhood period. Thus, responsivity is a potential target for language interventions through this age period.

Utilidad de la logopedia en la mejora del lenguaje en el tratamiento del síndrome del cromosoma X frágil en niños preescolares / Usefulness of speech therapy in improving language in the treatment of fragile X syndrome in preschool children

El síndrome del cromosoma X frágil (SXF) es la primera causa más frecuente de discapacidad intelectual y la segunda asociada a factores genéticos. Dado que existe una gran variabilidad en el fenotipo conductual que este síndrome presenta, se da la necesidad de realizar una adecuada evaluación de cada caso en particular. Se expone un estudio en el que se realiza un seguimiento exhaustivo de los niveles iniciales y de los logros conseguidos por 2 niños con SXF con mutación completa de 16 y 27 meses; uno recibe tratamiento logopédico y el otro no. Cuando se interpretan los resultados se encuentra que existe la necesidad de una evaluación individualizada que determine los déficits concretos que presenta cada niño en cada área de desarrollo, pues si bien se prevé, según la literatura científica, que existirán necesidades a nivel cognitivo y del lenguaje, se descubre que, aunque haya que intervenir en estas áreas, su necesidad se centra fundamentalmente a nivel motor y de autonomía, sobre todo en el segundo caso(AU)

Fragile X syndrome (FXS) is the most common cause-and the second genetic cause-of intellectual disability. There is wide variability in the behavioral phenotype associated with this syndrome and consequently evaluation should be individualized. We report the exhaustive initial evaluation, follow-up and achievements of two children (aged 16 and 27 months) with FXS with a full mutation. One child received speech therapy, while the other did not. Children with FXS should be individually assessed to determine their specific developmental impairments. Although the literature predicts that affected individuals will show cognitive and language deficits, we found that the two children assessed in this study required interventions aimed at improving motor skills and autonomy, especially the second child(AU)

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.

Parental reports on early language and motor milestones in fragile X syndrome with and without autism spectrum disorders.

OBJECTIVE: This study examined features of early language and motor milestones in children with fragile X syndrome (FXS) and contrasted these features with a diagnosis of Autism Spectrum Disorder (ASD) later in life in these children. METHODS: We retrospectively examined parental report of age of onset for walking and first words for primarily boys with FXS, both with ASD (FXS + ASD) and FXS-only. The diagnosis of ASD was established by DSM-IV criteria, which were complemented by the ADOS. The age of onset was analyzed as a continuous and categorical variable, which were compared to the upper limit of typically developing children. RESULTS: Individuals with FXS-only are more delayed in the onset of first words than first walks. The finding represents a pattern suggesting a continuum as robustly demonstrated in individuals with FXS + ASD vs. FXS-only. CONCLUSION: Our results support validity of FXS + ASD co-morbidity as a distinct phenotype in individuals with FXS.

Exploring the adult life of men and women with fragile X syndrome: results from a national survey.

Using data from a national family survey, the authors describe the adult lives (i.e., residence, employment, level of assistance needed with everyday life, friendships, and leisure activities) of 328 adults with the full mutation of the FMR1 gene and identify characteristics related to independence in these domains. Level of functional skills was the strongest predictor of independence in adult life for men, whereas ability to interact appropriately was the strongest predictor for women. Co-occurring mental health conditions influenced independence in adult life for men and women, in particular, autism spectrum disorders for men and affect problems for women. Services for adults with fragile X syndrome should not only target functional skills but interpersonal skills and co-occurring mental health conditions.