Dépouillements

Rare copy number variations affecting the synaptic gene DMXL2 in neurodevelopmental disorders / G. COSTAIN in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 3 p. Titre : Rare copy number variations affecting the synaptic gene DMXL2 in neurodevelopmental disorders Type de document : Texte imprimé et/ou numérique Auteurs : G. COSTAIN, Auteur ; S. WALKER, Auteur ; B. ARGIROPOULOS, Auteur ; D. A. BARIBEAU, Auteur ; A. S. BASSETT, Auteur ; E. BOOT, Auteur ; Koenraad DEVRIENDT, Auteur ; B. KELLAM, Auteur ; C. R. MARSHALL, Auteur ; A. PRASAD, Auteur ; M. A. SERRANO, Auteur ; D. J. STAVROPOULOS, Auteur ; H. TWEDE, Auteur ; J. R. VERMEESCH, Auteur ; J. A. S. VORSTMAN, Auteur ; Stephen SCHERER, Auteur Article en page(s) : 3 p. Langues : Anglais (eng) Mots-clés : Adhd  Autism  Copy number variation  Dmxl2  Grik5  Genome sequencing Index. décimale : PER Périodiques Résumé : BACKGROUND: Ultra-rare genetic variants, including non-recurrent copy number variations (CNVs) affecting important dosage-sensitive genes, are important contributors to the etiology of neurodevelopmental disorders (NDDs). Pairing family-based whole-genome sequencing (WGS) with detailed phenotype data can enable novel gene associations in NDDs. METHODS: We performed WGS of six members from a three-generation family, where three individuals each had a spectrum of features suggestive of a NDD. CNVs and sequence-level variants were identified and further investigated in disease and control databases. RESULTS: We identified a novel 252-kb deletion at 15q21 that overlaps the synaptic gene DMXL2 and the gene GLDN. The microdeletion segregated in NDD-affected individuals. Additional rare inherited and de novo sequence-level variants were found that may also be involved, including a missense change in GRIK5. Multiple CNVs and loss-of-function sequence variants affecting DMXL2 were discovered in additional unrelated individuals with a range of NDDs. CONCLUSIONS: Disruption of DMXL2 may predispose to NDDs including autism spectrum disorder. The robust interpretation of private variants requires a multifaceted approach that incorporates multigenerational pedigrees and genome-wide and population-scale data. En ligne : http://dx.doi.org/10.1186/s11689-019-9263-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386 [article] Rare copy number variations affecting the synaptic gene DMXL2 in neurodevelopmental disorders [Texte imprimé et/ou numérique] / G. COSTAIN, Auteur ; S. WALKER, Auteur ; B. ARGIROPOULOS, Auteur ; D. A. BARIBEAU, Auteur ; A. S. BASSETT, Auteur ; E. BOOT, Auteur ; Koenraad DEVRIENDT, Auteur ; B. KELLAM, Auteur ; C. R. MARSHALL, Auteur ; A. PRASAD, Auteur ; M. A. SERRANO, Auteur ; D. J. STAVROPOULOS, Auteur ; H. TWEDE, Auteur ; J. R. VERMEESCH, Auteur ; J. A. S. VORSTMAN, Auteur ; Stephen SCHERER, Auteur . - 3 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 3 p. Mots-clés : Adhd  Autism  Copy number variation  Dmxl2  Grik5  Genome sequencing Index. décimale : PER Périodiques Résumé : BACKGROUND: Ultra-rare genetic variants, including non-recurrent copy number variations (CNVs) affecting important dosage-sensitive genes, are important contributors to the etiology of neurodevelopmental disorders (NDDs). Pairing family-based whole-genome sequencing (WGS) with detailed phenotype data can enable novel gene associations in NDDs. METHODS: We performed WGS of six members from a three-generation family, where three individuals each had a spectrum of features suggestive of a NDD. CNVs and sequence-level variants were identified and further investigated in disease and control databases. RESULTS: We identified a novel 252-kb deletion at 15q21 that overlaps the synaptic gene DMXL2 and the gene GLDN. The microdeletion segregated in NDD-affected individuals. Additional rare inherited and de novo sequence-level variants were found that may also be involved, including a missense change in GRIK5. Multiple CNVs and loss-of-function sequence variants affecting DMXL2 were discovered in additional unrelated individuals with a range of NDDs. CONCLUSIONS: Disruption of DMXL2 may predispose to NDDs including autism spectrum disorder. The robust interpretation of private variants requires a multifaceted approach that incorporates multigenerational pedigrees and genome-wide and population-scale data. En ligne : http://dx.doi.org/10.1186/s11689-019-9263-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386

Differentiating social preference and social anxiety phenotypes in fragile X syndrome using an eye gaze analysis: a pilot study / M. P. HONG in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 1 p. Titre : Differentiating social preference and social anxiety phenotypes in fragile X syndrome using an eye gaze analysis: a pilot study Type de document : Texte imprimé et/ou numérique Auteurs : M. P. HONG, Auteur ; E. M. ECKERT, Auteur ; Ernest V. PEDAPATI, Auteur ; R. C. SHAFFER, Auteur ; K. C. DOMINICK, Auteur ; L. K. WINK, Auteur ; J. A. SWEENEY, Auteur ; C. A. ERICKSON, Auteur Article en page(s) : 1 p. Langues : Anglais (eng) Mots-clés : Autism  Eye tracking  Fragile X syndrome  Gaze aversion  Social anxiety  Social interest Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is the leading inherited cause of autism spectrum disorder, but there remains debate regarding the clinical presentation of social deficits in FXS. The aim of this study was to compare individuals with FXS to typically developing controls (TDC) and individuals with idiopathic autism spectrum disorder (ASD) across two social eye tracking paradigms. METHODS: Individuals with FXS and age- and gender-matched TDC and individuals with idiopathic ASD completed emotional face and social preference eye tracking tasks to evaluate gaze aversion and social interest, respectively. Participants completed a battery of cognitive testing and caregiver-reported measures for neurobehavioral characterization. RESULTS: Individuals with FXS exhibited reduced eye and increased mouth gaze to emotional faces compared to TDC. Gaze aversive findings were found to correlate with measures of anxiety, social communication deficits, and behavioral problems. In the social interest task, while individuals with idiopathic ASD showed significantly less social preference, individuals with FXS displayed social preference similar to TDC. CONCLUSIONS: These findings suggest fragile X syndrome social deficits center on social anxiety without the prominent reduction in social interest associated with autism spectrum disorder. Specifically designed eye tracking techniques clarify the nature of social deficits in fragile X syndrome and may have applications to improve phenotyping and evaluate interventions targeting social functioning impairments. En ligne : http://dx.doi.org/10.1186/s11689-019-9262-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386 [article] Differentiating social preference and social anxiety phenotypes in fragile X syndrome using an eye gaze analysis: a pilot study [Texte imprimé et/ou numérique] / M. P. HONG, Auteur ; E. M. ECKERT, Auteur ; Ernest V. PEDAPATI, Auteur ; R. C. SHAFFER, Auteur ; K. C. DOMINICK, Auteur ; L. K. WINK, Auteur ; J. A. SWEENEY, Auteur ; C. A. ERICKSON, Auteur . - 1 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 1 p. Mots-clés : Autism  Eye tracking  Fragile X syndrome  Gaze aversion  Social anxiety  Social interest Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is the leading inherited cause of autism spectrum disorder, but there remains debate regarding the clinical presentation of social deficits in FXS. The aim of this study was to compare individuals with FXS to typically developing controls (TDC) and individuals with idiopathic autism spectrum disorder (ASD) across two social eye tracking paradigms. METHODS: Individuals with FXS and age- and gender-matched TDC and individuals with idiopathic ASD completed emotional face and social preference eye tracking tasks to evaluate gaze aversion and social interest, respectively. Participants completed a battery of cognitive testing and caregiver-reported measures for neurobehavioral characterization. RESULTS: Individuals with FXS exhibited reduced eye and increased mouth gaze to emotional faces compared to TDC. Gaze aversive findings were found to correlate with measures of anxiety, social communication deficits, and behavioral problems. In the social interest task, while individuals with idiopathic ASD showed significantly less social preference, individuals with FXS displayed social preference similar to TDC. CONCLUSIONS: These findings suggest fragile X syndrome social deficits center on social anxiety without the prominent reduction in social interest associated with autism spectrum disorder. Specifically designed eye tracking techniques clarify the nature of social deficits in fragile X syndrome and may have applications to improve phenotyping and evaluate interventions targeting social functioning impairments. En ligne : http://dx.doi.org/10.1186/s11689-019-9262-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386

Static and dynamic postural control deficits in aging fragile X mental retardation 1 (FMR1) gene premutation carriers / Z. WANG in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 2 p. Titre : Static and dynamic postural control deficits in aging fragile X mental retardation 1 (FMR1) gene premutation carriers Type de document : Texte imprimé et/ou numérique Auteurs : Z. WANG, Auteur ; P. KHEMANI, Auteur ; Lauren M. SCHMITT, Auteur ; S. LUI, Auteur ; M. W. MOSCONI, Auteur Article en page(s) : 2 p. Langues : Anglais (eng) Mots-clés : Cerebellum  FMR1gene premutation allele  Fragile X mental retardation 1 (FMR1) gene  Fragile X-associated tremor/ataxia syndrome (FXTAS)  Postural control Index. décimale : PER Périodiques Résumé : BACKGROUND: Individuals with premutation alleles of the fragile X mental retardation 1 (FMR1) gene are at risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS) during aging. Characterization of motor issues associated with aging in FMR1 premutation carriers is needed to determine neurodegenerative processes and establish new biobehavioral indicators to help identify individuals at greatest risk of developing FXTAS. METHODS: We examined postural stability in 18 premutation carriers ages 46-77 years and 14 age-matched healthy controls. Participants completed a test of static stance and two tests of dynamic postural sway on a force platform to quantify postural variability and complexity. CGG repeat length was measured for each premutation carrier, and MRI and neurological evaluations were conducted to identify carriers who currently met criteria for FXTAS. Of the 18 premutation carriers, seven met criteria for definite/probable FXTAS (FXTAS+), seven showed no MRI or neurological signs of FXTAS (FXTAS-), and four were inconclusive due to insufficient data. RESULTS: Compared to controls, premutation carriers showed increased center of pressure (COP) variability in the mediolateral (COPML) direction during static stance and reduced COP variability in the anterior-posterior (COPAP) direction during dynamic AP sway. They also showed reductions in COPML complexity during each postural condition. FXTAS+ individuals showed reduced COPAP variability compared to FXTAS- carriers and healthy controls during dynamic AP sway. Across all carriers, increased sway variability during static stance and decreased sway variability in target directions during dynamic sways were associated with greater CGG repeat length and more severe neurologically rated posture and gait abnormalities. CONCLUSION: Our findings indicate that aging FMR1 premutation carriers show static and dynamic postural control deficits relative to healthy controls implicating degenerative processes of spinocerebellar and cerebellar-brainstem circuits that may be independent of or precede the onset of FXTAS. Our finding that FXTAS+ and FXTAS- premutation carriers differed on their level of intentional AP sway suggests that neural mechanisms of dynamic postural control may be differentially impacted in patients with FXTAS, and its measurement may be useful for rapidly and precisely identifying disease presence and onset. En ligne : http://dx.doi.org/10.1186/s11689-018-9261-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386 [article] Static and dynamic postural control deficits in aging fragile X mental retardation 1 (FMR1) gene premutation carriers [Texte imprimé et/ou numérique] / Z. WANG, Auteur ; P. KHEMANI, Auteur ; Lauren M. SCHMITT, Auteur ; S. LUI, Auteur ; M. W. MOSCONI, Auteur . - 2 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 2 p. Mots-clés : Cerebellum  FMR1gene premutation allele  Fragile X mental retardation 1 (FMR1) gene  Fragile X-associated tremor/ataxia syndrome (FXTAS)  Postural control Index. décimale : PER Périodiques Résumé : BACKGROUND: Individuals with premutation alleles of the fragile X mental retardation 1 (FMR1) gene are at risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS) during aging. Characterization of motor issues associated with aging in FMR1 premutation carriers is needed to determine neurodegenerative processes and establish new biobehavioral indicators to help identify individuals at greatest risk of developing FXTAS. METHODS: We examined postural stability in 18 premutation carriers ages 46-77 years and 14 age-matched healthy controls. Participants completed a test of static stance and two tests of dynamic postural sway on a force platform to quantify postural variability and complexity. CGG repeat length was measured for each premutation carrier, and MRI and neurological evaluations were conducted to identify carriers who currently met criteria for FXTAS. Of the 18 premutation carriers, seven met criteria for definite/probable FXTAS (FXTAS+), seven showed no MRI or neurological signs of FXTAS (FXTAS-), and four were inconclusive due to insufficient data. RESULTS: Compared to controls, premutation carriers showed increased center of pressure (COP) variability in the mediolateral (COPML) direction during static stance and reduced COP variability in the anterior-posterior (COPAP) direction during dynamic AP sway. They also showed reductions in COPML complexity during each postural condition. FXTAS+ individuals showed reduced COPAP variability compared to FXTAS- carriers and healthy controls during dynamic AP sway. Across all carriers, increased sway variability during static stance and decreased sway variability in target directions during dynamic sways were associated with greater CGG repeat length and more severe neurologically rated posture and gait abnormalities. CONCLUSION: Our findings indicate that aging FMR1 premutation carriers show static and dynamic postural control deficits relative to healthy controls implicating degenerative processes of spinocerebellar and cerebellar-brainstem circuits that may be independent of or precede the onset of FXTAS. Our finding that FXTAS+ and FXTAS- premutation carriers differed on their level of intentional AP sway suggests that neural mechanisms of dynamic postural control may be differentially impacted in patients with FXTAS, and its measurement may be useful for rapidly and precisely identifying disease presence and onset. En ligne : http://dx.doi.org/10.1186/s11689-018-9261-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386

Adaptation to different communicative contexts: an eye tracking study of autistic adults / Julia PARISH-MORRIS in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 5 p. Titre : Adaptation to different communicative contexts: an eye tracking study of autistic adults Type de document : Texte imprimé et/ou numérique Auteurs : Julia PARISH-MORRIS, Auteur ; Ashley A. PALLATHRA, Auteur ; E. FERGUSON, Auteur ; B. B. MADDOX, Auteur ; A. POMYKACZ, Auteur ; L. S. PEREZ, Auteur ; Leila BATEMAN, Auteur ; J. PANDEY, Auteur ; Robert T. SCHULTZ, Auteur ; Edward S. BRODKIN, Auteur Article en page(s) : 5 p. Langues : Anglais (eng) Mots-clés : Adults  Autism spectrum disorder  Eye gaze  Face processing/perception Index. décimale : PER Périodiques Résumé : BACKGROUND: Learning through social observation (i.e., watching other people interact) lays the foundation for later social skills and social cognition. However, social situations are often complex, and humans are only capable of attending to one aspect of a scene at a time. How do people choose where to allocate their visual resources when viewing complex social scenarios? For typically developing (TD) individuals, faces are often given priority. Depending upon context, however, it may be more useful to attend to other aspects of the environment, such as hands, tools, or background objects. Previous studies reported reduced face looking in individuals with autism spectrum disorder (ASD), but modulation of visual attention in response to contextual differences (e.g., according to social richness, or the presence/absence of communicative behaviors between two people) has only briefly been explored. In this study, we used eye-tracking technology to test the extent to which ASD adults and TD adults use social context to guide their gaze behavior. METHODS: Fifty-five adults participated (28 with ASD). The location and duration of participants' gaze were recorded while they watched a series of naturalistic social videos. Half of the videos depicted two people engaging in non-verbal communication (rich social scenes) while playing with toys. The other half depicted two people playing with toys separately, not interacting with each other (lean social scenes). RESULTS: ASD and TD adults both increased their attention to faces in communicative contexts (rich social scenes) as compared to non-communicative contexts (lean social scenes). However, TD adults increased their attention to faces significantly more when watching two people communicate than did ASD adults, who increased their attention to a lesser degree. Further analysis revealed that ASD adults persisted in looking at hands and toys, even when observing two people communicate in a rich social scene. CONCLUSIONS: Diminished gaze to faces when observing two people communicating may lead to fewer opportunities for social learning and subsequent reductions in social knowledge. Naturalistic measures of contextual modulation could help identify areas of need for individuals learning about the social world and could become treatment targets to improve everyday social learning. En ligne : https://dx.doi.org/10.1186/s11689-019-9265-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Adaptation to different communicative contexts: an eye tracking study of autistic adults [Texte imprimé et/ou numérique] / Julia PARISH-MORRIS, Auteur ; Ashley A. PALLATHRA, Auteur ; E. FERGUSON, Auteur ; B. B. MADDOX, Auteur ; A. POMYKACZ, Auteur ; L. S. PEREZ, Auteur ; Leila BATEMAN, Auteur ; J. PANDEY, Auteur ; Robert T. SCHULTZ, Auteur ; Edward S. BRODKIN, Auteur . - 5 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 5 p. Mots-clés : Adults  Autism spectrum disorder  Eye gaze  Face processing/perception Index. décimale : PER Périodiques Résumé : BACKGROUND: Learning through social observation (i.e., watching other people interact) lays the foundation for later social skills and social cognition. However, social situations are often complex, and humans are only capable of attending to one aspect of a scene at a time. How do people choose where to allocate their visual resources when viewing complex social scenarios? For typically developing (TD) individuals, faces are often given priority. Depending upon context, however, it may be more useful to attend to other aspects of the environment, such as hands, tools, or background objects. Previous studies reported reduced face looking in individuals with autism spectrum disorder (ASD), but modulation of visual attention in response to contextual differences (e.g., according to social richness, or the presence/absence of communicative behaviors between two people) has only briefly been explored. In this study, we used eye-tracking technology to test the extent to which ASD adults and TD adults use social context to guide their gaze behavior. METHODS: Fifty-five adults participated (28 with ASD). The location and duration of participants' gaze were recorded while they watched a series of naturalistic social videos. Half of the videos depicted two people engaging in non-verbal communication (rich social scenes) while playing with toys. The other half depicted two people playing with toys separately, not interacting with each other (lean social scenes). RESULTS: ASD and TD adults both increased their attention to faces in communicative contexts (rich social scenes) as compared to non-communicative contexts (lean social scenes). However, TD adults increased their attention to faces significantly more when watching two people communicate than did ASD adults, who increased their attention to a lesser degree. Further analysis revealed that ASD adults persisted in looking at hands and toys, even when observing two people communicate in a rich social scene. CONCLUSIONS: Diminished gaze to faces when observing two people communicating may lead to fewer opportunities for social learning and subsequent reductions in social knowledge. Naturalistic measures of contextual modulation could help identify areas of need for individuals learning about the social world and could become treatment targets to improve everyday social learning. En ligne : https://dx.doi.org/10.1186/s11689-019-9265-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Cognitive training for children and adolescents with fragile X syndrome: a randomized controlled trial of Cogmed / D. HESSL in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 4 p. Titre : Cognitive training for children and adolescents with fragile X syndrome: a randomized controlled trial of Cogmed Type de document : Texte imprimé et/ou numérique Auteurs : D. HESSL, Auteur ; Julie B. SCHWEITZER, Auteur ; D. V. NGUYEN, Auteur ; Y. A. MCLENNAN, Auteur ; C. JOHNSTON, Auteur ; R. SHICKMAN, Auteur ; Y. CHEN, Auteur Article en page(s) : 4 p. Langues : Anglais (eng) Mots-clés : FMR1 gene  Fragile X mental retardation protein  Intellectual disability  Treatment  Working memory Index. décimale : PER Périodiques Résumé : 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 . En ligne : https://dx.doi.org/10.1186/s11689-019-9264-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Cognitive training for children and adolescents with fragile X syndrome: a randomized controlled trial of Cogmed [Texte imprimé et/ou numérique] / D. HESSL, Auteur ; Julie B. SCHWEITZER, Auteur ; D. V. NGUYEN, Auteur ; Y. A. MCLENNAN, Auteur ; C. JOHNSTON, Auteur ; R. SHICKMAN, Auteur ; Y. CHEN, Auteur . - 4 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 4 p. Mots-clés : FMR1 gene  Fragile X mental retardation protein  Intellectual disability  Treatment  Working memory Index. décimale : PER Périodiques Résumé : 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 . En ligne : https://dx.doi.org/10.1186/s11689-019-9264-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Lifespan trajectory of affect in Cornelia de Lange syndrome: towards a neurobiological hypothesis / L. GROVES in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 6 p. Titre : Lifespan trajectory of affect in Cornelia de Lange syndrome: towards a neurobiological hypothesis Type de document : Texte imprimé et/ou numérique Auteurs : L. GROVES, Auteur ; J. MOSS, Auteur ; Hayley CRAWFORD, Auteur ; L. NELSON, Auteur ; C. STINTON, Auteur ; G. SINGLA, Auteur ; C. OLIVER, Auteur Article en page(s) : 6 p. Langues : Anglais (eng) Mots-clés : Affect  Cornelia de Lange syndrome  Fragile X syndrome  Mood  Trajectory Index. décimale : PER Périodiques Résumé : BACKGROUND: Depressive symptomology and low affect are comparatively common in individuals with genetic disorders such as Cornelia de Lange syndrome. However, lifespan trajectories and associated person characteristics have not been examined. In this study, the trajectories for affect and associated behavioural characteristics were investigated in individuals with Cornelia de Lange syndrome with individuals with fragile X syndrome (FXS) comparable for chronological age and total number of behavioural indicators of ASD included for the purpose of contrast. METHODS: A 7-year longitudinal study of affect (mood, interest and pleasure) was conducted in individuals with CdLS (n = 44) and FXS (n = 95). The trajectories of low affect were explored, as well as associations between Time 1 behavioural characteristics and affect at Time 1 and Time 3 (7 years later). RESULTS: The CdLS group were lower in mood than the FXS group overall (p < .001). Interest and pleasure scores showed a significant decline over the lifespan for individuals with CdLS (p < .001) but not the FXS group. Lower level of ability at Time 1 was associated with lower mood at Time 1 and Time 3 in the FXS group only. Higher levels of ASD symptomology at Time 1 were associated with low mood and interest and pleasure in both syndrome groups at Time 1 and Time 3. Greater insistence on sameness at Time 1 was associated with lower mood at Time 1 in the FXS group and lower interest and pleasure at Time 1 and Time 3 in the CdLS group. CONCLUSIONS: Low affect in specific genetic syndromes may be associated with differing lifespan trajectories and behavioural profiles. Specifically, individuals with CdLS appear at risk for experiencing declines in levels of interest and pleasure whereas individuals with FXS show no significant change in the level of affect with age. En ligne : https://dx.doi.org/10.1186/s11689-019-9269-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Lifespan trajectory of affect in Cornelia de Lange syndrome: towards a neurobiological hypothesis [Texte imprimé et/ou numérique] / L. GROVES, Auteur ; J. MOSS, Auteur ; Hayley CRAWFORD, Auteur ; L. NELSON, Auteur ; C. STINTON, Auteur ; G. SINGLA, Auteur ; C. OLIVER, Auteur . - 6 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 6 p. Mots-clés : Affect  Cornelia de Lange syndrome  Fragile X syndrome  Mood  Trajectory Index. décimale : PER Périodiques Résumé : BACKGROUND: Depressive symptomology and low affect are comparatively common in individuals with genetic disorders such as Cornelia de Lange syndrome. However, lifespan trajectories and associated person characteristics have not been examined. In this study, the trajectories for affect and associated behavioural characteristics were investigated in individuals with Cornelia de Lange syndrome with individuals with fragile X syndrome (FXS) comparable for chronological age and total number of behavioural indicators of ASD included for the purpose of contrast. METHODS: A 7-year longitudinal study of affect (mood, interest and pleasure) was conducted in individuals with CdLS (n = 44) and FXS (n = 95). The trajectories of low affect were explored, as well as associations between Time 1 behavioural characteristics and affect at Time 1 and Time 3 (7 years later). RESULTS: The CdLS group were lower in mood than the FXS group overall (p < .001). Interest and pleasure scores showed a significant decline over the lifespan for individuals with CdLS (p < .001) but not the FXS group. Lower level of ability at Time 1 was associated with lower mood at Time 1 and Time 3 in the FXS group only. Higher levels of ASD symptomology at Time 1 were associated with low mood and interest and pleasure in both syndrome groups at Time 1 and Time 3. Greater insistence on sameness at Time 1 was associated with lower mood at Time 1 in the FXS group and lower interest and pleasure at Time 1 and Time 3 in the CdLS group. CONCLUSIONS: Low affect in specific genetic syndromes may be associated with differing lifespan trajectories and behavioural profiles. Specifically, individuals with CdLS appear at risk for experiencing declines in levels of interest and pleasure whereas individuals with FXS show no significant change in the level of affect with age. En ligne : https://dx.doi.org/10.1186/s11689-019-9269-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

In the line-up: deleted genes associated with DiGeorge/22q11.2 deletion syndrome: are they all suspects? / Z. MOTAHARI in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 7 p. Titre : In the line-up: deleted genes associated with DiGeorge/22q11.2 deletion syndrome: are they all suspects? Type de document : Texte imprimé et/ou numérique Auteurs : Z. MOTAHARI, Auteur ; S. A. MOODY, Auteur ; T. M. MAYNARD, Auteur ; A. S. LAMANTIA, Auteur Article en page(s) : 7 p. Langues : Anglais (eng) Mots-clés : 22q11DS  Cardiovascular  Cognition  Copy number variants  Craniofacial  Neural development  Polygenic Index. décimale : PER Périodiques Résumé : BACKGROUND: 22q11.2 deletion syndrome (22q11DS), a copy number variation (CNV) disorder, occurs in approximately 1:4000 live births due to a heterozygous microdeletion at position 11.2 (proximal) on the q arm of human chromosome 22 (hChr22) (McDonald-McGinn and Sullivan, Medicine 90:1-18, 2011). This disorder was known as DiGeorge syndrome, Velo-cardio-facial syndrome (VCFS) or conotruncal anomaly face syndrome (CTAF) based upon diagnostic cardiovascular, pharyngeal, and craniofacial anomalies (McDonald-McGinn and Sullivan, Medicine 90:1-18, 2011; Burn et al., J Med Genet 30:822-4, 1993) before this phenotypic spectrum was associated with 22q11.2 CNVs. Subsequently, 22q11.2 deletion emerged as a major genomic lesion associated with vulnerability for several clinically defined behavioral deficits common to a number of neurodevelopmental disorders (Fernandez et al., Principles of Developmental Genetics, 2015; Robin and Shprintzen, J Pediatr 147:90-6, 2005; Schneider et al., Am J Psychiatry 171:627-39, 2014). RESULTS: The mechanistic relationships between heterozygously deleted 22q11.2 genes and 22q11DS phenotypes are still unknown. We assembled a comprehensive "line-up" of the 36 protein coding loci in the 1.5 Mb minimal critical deleted region on hChr22q11.2, plus 20 protein coding loci in the distal 1.5 Mb that defines the 3 Mb typical 22q11DS deletion. We categorized candidates based upon apparent primary cell biological functions. We analyzed 41 of these genes that encode known proteins to determine whether haploinsufficiency of any single 22q11.2 gene-a one gene to one phenotype correspondence due to heterozygous deletion restricted to that locus-versus complex multigenic interactions can account for single or multiple 22q11DS phenotypes. CONCLUSIONS: Our 22q11.2 functional genomic assessment does not support current theories of single gene haploinsufficiency for one or all 22q11DS phenotypes. Shared molecular functions, convergence on fundamental cell biological processes, and related consequences of individual 22q11.2 genes point to a matrix of multigenic interactions due to diminished 22q11.2 gene dosage. These interactions target fundamental cellular mechanisms essential for development, maturation, or homeostasis at subsets of 22q11DS phenotypic sites. En ligne : https://dx.doi.org/10.1186/s11689-019-9267-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] In the line-up: deleted genes associated with DiGeorge/22q11.2 deletion syndrome: are they all suspects? [Texte imprimé et/ou numérique] / Z. MOTAHARI, Auteur ; S. A. MOODY, Auteur ; T. M. MAYNARD, Auteur ; A. S. LAMANTIA, Auteur . - 7 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 7 p. Mots-clés : 22q11DS  Cardiovascular  Cognition  Copy number variants  Craniofacial  Neural development  Polygenic Index. décimale : PER Périodiques Résumé : BACKGROUND: 22q11.2 deletion syndrome (22q11DS), a copy number variation (CNV) disorder, occurs in approximately 1:4000 live births due to a heterozygous microdeletion at position 11.2 (proximal) on the q arm of human chromosome 22 (hChr22) (McDonald-McGinn and Sullivan, Medicine 90:1-18, 2011). This disorder was known as DiGeorge syndrome, Velo-cardio-facial syndrome (VCFS) or conotruncal anomaly face syndrome (CTAF) based upon diagnostic cardiovascular, pharyngeal, and craniofacial anomalies (McDonald-McGinn and Sullivan, Medicine 90:1-18, 2011; Burn et al., J Med Genet 30:822-4, 1993) before this phenotypic spectrum was associated with 22q11.2 CNVs. Subsequently, 22q11.2 deletion emerged as a major genomic lesion associated with vulnerability for several clinically defined behavioral deficits common to a number of neurodevelopmental disorders (Fernandez et al., Principles of Developmental Genetics, 2015; Robin and Shprintzen, J Pediatr 147:90-6, 2005; Schneider et al., Am J Psychiatry 171:627-39, 2014). RESULTS: The mechanistic relationships between heterozygously deleted 22q11.2 genes and 22q11DS phenotypes are still unknown. We assembled a comprehensive "line-up" of the 36 protein coding loci in the 1.5 Mb minimal critical deleted region on hChr22q11.2, plus 20 protein coding loci in the distal 1.5 Mb that defines the 3 Mb typical 22q11DS deletion. We categorized candidates based upon apparent primary cell biological functions. We analyzed 41 of these genes that encode known proteins to determine whether haploinsufficiency of any single 22q11.2 gene-a one gene to one phenotype correspondence due to heterozygous deletion restricted to that locus-versus complex multigenic interactions can account for single or multiple 22q11DS phenotypes. CONCLUSIONS: Our 22q11.2 functional genomic assessment does not support current theories of single gene haploinsufficiency for one or all 22q11DS phenotypes. Shared molecular functions, convergence on fundamental cell biological processes, and related consequences of individual 22q11.2 genes point to a matrix of multigenic interactions due to diminished 22q11.2 gene dosage. These interactions target fundamental cellular mechanisms essential for development, maturation, or homeostasis at subsets of 22q11DS phenotypic sites. En ligne : https://dx.doi.org/10.1186/s11689-019-9267-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Using kinematic analyses to explore sensorimotor control impairments in children with 22q11.2 deletion syndrome / A. C. CUNNINGHAM in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 8 p. Titre : Using kinematic analyses to explore sensorimotor control impairments in children with 22q11.2 deletion syndrome Type de document : Texte imprimé et/ou numérique Auteurs : A. C. CUNNINGHAM, Auteur ; L. HILL, Auteur ; M. MON-WILLIAMS, Auteur ; K. J. PEALL, Auteur ; D. E. J. LINDEN, Auteur ; J. HALL, Auteur ; M. J. OWEN, Auteur ; M. B. M. VAN DEN BREE, Auteur Article en page(s) : 8 p. Langues : Anglais (eng) Mots-clés : 22q11.2 deletion syndrome  Adhd  Asd  Anxiety  Coordination  Movement difficulties Index. décimale : PER Périodiques Résumé : BACKGROUND: The 22q11.2 deletion is associated with psychiatric and behavioural disorders, intellectual disability and multiple physical abnormalities. Recent research also indicates impaired coordination skills may be part of the clinical phenotype. This study aimed to characterise sensorimotor control abilities in children with 22q11.2 deletion syndrome (22q11.2DS) and investigate their relationships with co-occurring IQ impairments and psychopathology. METHODS: Fifty-four children with 22q11.2DS and 24 unaffected sibling controls, comparable in age and gender, underwent kinematic analysis of their hand movements, whilst performing a battery of three visuo-manual coordination tasks that measured their tracking, aiming and steering abilities. Additionally, standardised assessments of full-scale IQ (FSIQ), attention deficit hyperactivity disorder, indicative autism spectrum disorder (ASD) and anxiety disorder symptomatology were conducted. RESULTS: Children with 22q11.2DS showed deficits on seven of eight kinematic descriptors of movement quality across the three coordination tasks, compared to controls. Within 22q11.2DS cases, the extent of impairment on only three kinematic descriptors was significantly related to FSIQ after correction for multiple testing. Moreover, only error whilst visuo-manually tracking was nominally associated with ADHD symptom counts. CONCLUSIONS: Impairments in sensorimotor control are seen on a range of visuo-manual tasks in children with 22q11.2DS but the extent of these impairments are largely unrelated to the severity of other psychopathological and intellectual impairments commonly found in children with 22q11.2DS. En ligne : https://dx.doi.org/10.1186/s11689-019-9271-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Using kinematic analyses to explore sensorimotor control impairments in children with 22q11.2 deletion syndrome [Texte imprimé et/ou numérique] / A. C. CUNNINGHAM, Auteur ; L. HILL, Auteur ; M. MON-WILLIAMS, Auteur ; K. J. PEALL, Auteur ; D. E. J. LINDEN, Auteur ; J. HALL, Auteur ; M. J. OWEN, Auteur ; M. B. M. VAN DEN BREE, Auteur . - 8 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 8 p. Mots-clés : 22q11.2 deletion syndrome  Adhd  Asd  Anxiety  Coordination  Movement difficulties Index. décimale : PER Périodiques Résumé : BACKGROUND: The 22q11.2 deletion is associated with psychiatric and behavioural disorders, intellectual disability and multiple physical abnormalities. Recent research also indicates impaired coordination skills may be part of the clinical phenotype. This study aimed to characterise sensorimotor control abilities in children with 22q11.2 deletion syndrome (22q11.2DS) and investigate their relationships with co-occurring IQ impairments and psychopathology. METHODS: Fifty-four children with 22q11.2DS and 24 unaffected sibling controls, comparable in age and gender, underwent kinematic analysis of their hand movements, whilst performing a battery of three visuo-manual coordination tasks that measured their tracking, aiming and steering abilities. Additionally, standardised assessments of full-scale IQ (FSIQ), attention deficit hyperactivity disorder, indicative autism spectrum disorder (ASD) and anxiety disorder symptomatology were conducted. RESULTS: Children with 22q11.2DS showed deficits on seven of eight kinematic descriptors of movement quality across the three coordination tasks, compared to controls. Within 22q11.2DS cases, the extent of impairment on only three kinematic descriptors was significantly related to FSIQ after correction for multiple testing. Moreover, only error whilst visuo-manually tracking was nominally associated with ADHD symptom counts. CONCLUSIONS: Impairments in sensorimotor control are seen on a range of visuo-manual tasks in children with 22q11.2DS but the extent of these impairments are largely unrelated to the severity of other psychopathological and intellectual impairments commonly found in children with 22q11.2DS. En ligne : https://dx.doi.org/10.1186/s11689-019-9271-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Lesser suppression of response to bright visual stimuli and visual abnormality in children with autism spectrum disorder: a magnetoencephalographic study / S. AOKI in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 9 p. Titre : Lesser suppression of response to bright visual stimuli and visual abnormality in children with autism spectrum disorder: a magnetoencephalographic study Type de document : Texte imprimé et/ou numérique Auteurs : S. AOKI, Auteur ; Kuriko KAGITANI-SHIMONO, Auteur ; J. MATSUZAKI, Auteur ; R. HANAIE, Auteur ; M. NAKANISHI, Auteur ; K. TOMINAGA, Auteur ; Y. NAGAI, Auteur ; I. MOHRI, Auteur ; M. TANIIKE, Auteur Article en page(s) : 9 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorders (ASD)  Bright visual stimuli  Magnetoencephalography (MEG)  Neural suppression  Supramarginal gyrus (SMG)  Visual abnormality Index. décimale : PER Périodiques Résumé : BACKGROUND: Visual abnormality is a common sensory impairment in autism spectrum disorder (ASD), which may cause behavioral problems. However, only a few studies exist on the neural features corresponding to the visual symptoms in ASD. The purpose of this study was to investigate the relationship between cortical responses to visual stimuli and visual abnormality to examine the neurophysiological mechanisms of the visual abnormality in ASD. METHODS: Twenty-two high-functioning children with ASD (10.95 +/- 2.01 years old) and 23 age-matched typically developing (TD) children (10.13 +/- 2.80 years old) participated in this study. We measured the cortical responses (i.e., activated intensity and attenuation ratio) elicited by the Original visual image and other two types of bright images (the Dot noise or Blind image, which includes overlapped particles onto the Original image or the enhanced-brightness version of the Original image, respectively) using magnetoencephalography. RESULTS: The severity of visual abnormalities was significantly associated with behavioral problems in children with ASD. In addition, we found the increased cortical activation in response to the Original image in the left supramarginal gyrus (SMG) and middle temporal gyrus in children with ASD. However, there were no inter-group differences in the primary visual and medial orbitofrontal cortices. Furthermore, when we compared cortical responses according to the type of images, children with ASD showed lesser attenuation of the activated intensities than children with TD in response to the bright images compared with the Original image in the right SMG. These attenuation ratios (Dot noise/Original and Blind/Original) were also associated with the severity of visual abnormalities. CONCLUSIONS: Our results show that dysfunction of stimulus-driven neural suppression plays a crucial role in the neural mechanism of visual abnormality in children with ASD. To the best of our knowledge, this is the first magnetoencephalography study to demonstrate the association between the severity of visual abnormality and lower attenuation ratios in children with ASD. Our results contribute to the knowledge of the mechanisms underlying visual abnormality in children with ASD, and may therefore lead to more effective diagnosis and earlier intervention. En ligne : https://dx.doi.org/10.1186/s11689-019-9266-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Lesser suppression of response to bright visual stimuli and visual abnormality in children with autism spectrum disorder: a magnetoencephalographic study [Texte imprimé et/ou numérique] / S. AOKI, Auteur ; Kuriko KAGITANI-SHIMONO, Auteur ; J. MATSUZAKI, Auteur ; R. HANAIE, Auteur ; M. NAKANISHI, Auteur ; K. TOMINAGA, Auteur ; Y. NAGAI, Auteur ; I. MOHRI, Auteur ; M. TANIIKE, Auteur . - 9 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 9 p. Mots-clés : Autism spectrum disorders (ASD)  Bright visual stimuli  Magnetoencephalography (MEG)  Neural suppression  Supramarginal gyrus (SMG)  Visual abnormality Index. décimale : PER Périodiques Résumé : BACKGROUND: Visual abnormality is a common sensory impairment in autism spectrum disorder (ASD), which may cause behavioral problems. However, only a few studies exist on the neural features corresponding to the visual symptoms in ASD. The purpose of this study was to investigate the relationship between cortical responses to visual stimuli and visual abnormality to examine the neurophysiological mechanisms of the visual abnormality in ASD. METHODS: Twenty-two high-functioning children with ASD (10.95 +/- 2.01 years old) and 23 age-matched typically developing (TD) children (10.13 +/- 2.80 years old) participated in this study. We measured the cortical responses (i.e., activated intensity and attenuation ratio) elicited by the Original visual image and other two types of bright images (the Dot noise or Blind image, which includes overlapped particles onto the Original image or the enhanced-brightness version of the Original image, respectively) using magnetoencephalography. RESULTS: The severity of visual abnormalities was significantly associated with behavioral problems in children with ASD. In addition, we found the increased cortical activation in response to the Original image in the left supramarginal gyrus (SMG) and middle temporal gyrus in children with ASD. However, there were no inter-group differences in the primary visual and medial orbitofrontal cortices. Furthermore, when we compared cortical responses according to the type of images, children with ASD showed lesser attenuation of the activated intensities than children with TD in response to the bright images compared with the Original image in the right SMG. These attenuation ratios (Dot noise/Original and Blind/Original) were also associated with the severity of visual abnormalities. CONCLUSIONS: Our results show that dysfunction of stimulus-driven neural suppression plays a crucial role in the neural mechanism of visual abnormality in children with ASD. To the best of our knowledge, this is the first magnetoencephalography study to demonstrate the association between the severity of visual abnormality and lower attenuation ratios in children with ASD. Our results contribute to the knowledge of the mechanisms underlying visual abnormality in children with ASD, and may therefore lead to more effective diagnosis and earlier intervention. En ligne : https://dx.doi.org/10.1186/s11689-019-9266-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Impaired neurodevelopmental pathways in autism spectrum disorder: a review of signaling mechanisms and crosstalk / S. KUMAR in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 10 p. Titre : Impaired neurodevelopmental pathways in autism spectrum disorder: a review of signaling mechanisms and crosstalk Type de document : Texte imprimé et/ou numérique Auteurs : S. KUMAR, Auteur ; K. REYNOLDS, Auteur ; Y. JI, Auteur ; R. GU, Auteur ; S. RAI, Auteur ; C. J. ZHOU, Auteur Article en page(s) : 10 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  BMP/TGF-beta  Fgf  Neurodevelopmental disorders  Retinoic acid (RA)  Shh  Signaling crosstalk  Wnt Index. décimale : PER Périodiques Résumé : BACKGROUND: The development of an autistic brain is a highly complex process as evident from the involvement of various genetic and non-genetic factors in the etiology of the autism spectrum disorder (ASD). Despite being a multifactorial neurodevelopmental disorder, autistic patients display a few key characteristics, such as the impaired social interactions and elevated repetitive behaviors, suggesting the perturbation of specific neuronal circuits resulted from abnormal signaling pathways during brain development in ASD. A comprehensive review for autistic signaling mechanisms and interactions may provide a better understanding of ASD etiology and treatment. MAIN BODY: Recent studies on genetic models and ASD patients with several different mutated genes revealed the dysregulation of several key signaling pathways, such as WNT, BMP, SHH, and retinoic acid (RA) signaling. Although no direct evidence of dysfunctional FGF or TGF-beta signaling in ASD has been reported so far, a few examples of indirect evidence can be found. This review article summarizes how various genetic and non-genetic factors which have been reported contributing to ASD interact with WNT, BMP/TGF-beta, SHH, FGF, and RA signaling pathways. The autism-associated gene ubiquitin-protein ligase E3A (UBE3A) has been reported to influence WNT, BMP, and RA signaling pathways, suggesting crosstalk between various signaling pathways during autistic brain development. Finally, the article comments on what further studies could be performed to gain deeper insights into the understanding of perturbed signaling pathways in the etiology of ASD. CONCLUSION: The understanding of mechanisms behind various signaling pathways in the etiology of ASD may help to facilitate the identification of potential therapeutic targets and design of new treatment methods. En ligne : https://dx.doi.org/10.1186/s11689-019-9268-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Impaired neurodevelopmental pathways in autism spectrum disorder: a review of signaling mechanisms and crosstalk [Texte imprimé et/ou numérique] / S. KUMAR, Auteur ; K. REYNOLDS, Auteur ; Y. JI, Auteur ; R. GU, Auteur ; S. RAI, Auteur ; C. J. ZHOU, Auteur . - 10 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 10 p. Mots-clés : Autism spectrum disorder  BMP/TGF-beta  Fgf  Neurodevelopmental disorders  Retinoic acid (RA)  Shh  Signaling crosstalk  Wnt Index. décimale : PER Périodiques Résumé : BACKGROUND: The development of an autistic brain is a highly complex process as evident from the involvement of various genetic and non-genetic factors in the etiology of the autism spectrum disorder (ASD). Despite being a multifactorial neurodevelopmental disorder, autistic patients display a few key characteristics, such as the impaired social interactions and elevated repetitive behaviors, suggesting the perturbation of specific neuronal circuits resulted from abnormal signaling pathways during brain development in ASD. A comprehensive review for autistic signaling mechanisms and interactions may provide a better understanding of ASD etiology and treatment. MAIN BODY: Recent studies on genetic models and ASD patients with several different mutated genes revealed the dysregulation of several key signaling pathways, such as WNT, BMP, SHH, and retinoic acid (RA) signaling. Although no direct evidence of dysfunctional FGF or TGF-beta signaling in ASD has been reported so far, a few examples of indirect evidence can be found. This review article summarizes how various genetic and non-genetic factors which have been reported contributing to ASD interact with WNT, BMP/TGF-beta, SHH, FGF, and RA signaling pathways. The autism-associated gene ubiquitin-protein ligase E3A (UBE3A) has been reported to influence WNT, BMP, and RA signaling pathways, suggesting crosstalk between various signaling pathways during autistic brain development. Finally, the article comments on what further studies could be performed to gain deeper insights into the understanding of perturbed signaling pathways in the etiology of ASD. CONCLUSION: The understanding of mechanisms behind various signaling pathways in the etiology of ASD may help to facilitate the identification of potential therapeutic targets and design of new treatment methods. En ligne : https://dx.doi.org/10.1186/s11689-019-9268-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Novel pathogenic variants and multiple molecular diagnoses in neurodevelopmental disorders / J. TRINH in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 11 p. Titre : Novel pathogenic variants and multiple molecular diagnoses in neurodevelopmental disorders Type de document : Texte imprimé et/ou numérique Auteurs : J. TRINH, Auteur ; K. K. KANDASWAMY, Auteur ; M. WERBER, Auteur ; M. E. R. WEISS, Auteur ; G. OPREA, Auteur ; S. KISHORE, Auteur ; K. LOHMANN, Auteur ; A. ROLFS, Auteur Article en page(s) : 11 p. Langues : Anglais (eng) Mots-clés : De novo variants  Neurodevelopmental disorders  Trio exome sequencing Index. décimale : PER Périodiques Résumé : BACKGROUND: Rare denovo variants represent a significant cause of neurodevelopmental delay and intellectual disability (ID). METHODS: Exome sequencing was performed on 4351 patients with global developmental delay, seizures, microcephaly, macrocephaly, motor delay, delayed speech and language development, or ID according to Human Phenotype Ontology (HPO) terms. All patients had previously undergone whole exome sequencing as part of diagnostic genetic testing with a focus on variants in genes implicated in neurodevelopmental disorders up to January 2017. This resulted in a genetic diagnosis in 1336 of the patients. In this study, we specifically searched for variants in 14 recently implicated novel neurodevelopmental disorder (NDD) genes. RESULTS: We identified 65 rare, protein-changing variants in 11 of these 14 novel candidate genes. Fourteen variants in CDK13, CHD4, KCNQ3, KMT5B, TCF20, and ZBTB18 were scored pathogenic or likely pathogenic. Of note, two of these patients had a previously identified cause of their disease, and thus, multiple molecular diagnoses were made including pathogenic/likely pathogenic variants in FOXG1 and CDK13 or in TMEM237 and KMT5B. CONCLUSIONS: Looking for pathogenic variants in newly identified NDD genes enabled us to provide a molecular diagnosis to 14 patients and their close relatives and caregivers. This underlines the relevance of re-evaluation of existing exome data on a regular basis to improve the diagnostic yield and serve the needs of our patients. En ligne : https://dx.doi.org/10.1186/s11689-019-9270-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Novel pathogenic variants and multiple molecular diagnoses in neurodevelopmental disorders [Texte imprimé et/ou numérique] / J. TRINH, Auteur ; K. K. KANDASWAMY, Auteur ; M. WERBER, Auteur ; M. E. R. WEISS, Auteur ; G. OPREA, Auteur ; S. KISHORE, Auteur ; K. LOHMANN, Auteur ; A. ROLFS, Auteur . - 11 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 11 p. Mots-clés : De novo variants  Neurodevelopmental disorders  Trio exome sequencing Index. décimale : PER Périodiques Résumé : BACKGROUND: Rare denovo variants represent a significant cause of neurodevelopmental delay and intellectual disability (ID). METHODS: Exome sequencing was performed on 4351 patients with global developmental delay, seizures, microcephaly, macrocephaly, motor delay, delayed speech and language development, or ID according to Human Phenotype Ontology (HPO) terms. All patients had previously undergone whole exome sequencing as part of diagnostic genetic testing with a focus on variants in genes implicated in neurodevelopmental disorders up to January 2017. This resulted in a genetic diagnosis in 1336 of the patients. In this study, we specifically searched for variants in 14 recently implicated novel neurodevelopmental disorder (NDD) genes. RESULTS: We identified 65 rare, protein-changing variants in 11 of these 14 novel candidate genes. Fourteen variants in CDK13, CHD4, KCNQ3, KMT5B, TCF20, and ZBTB18 were scored pathogenic or likely pathogenic. Of note, two of these patients had a previously identified cause of their disease, and thus, multiple molecular diagnoses were made including pathogenic/likely pathogenic variants in FOXG1 and CDK13 or in TMEM237 and KMT5B. CONCLUSIONS: Looking for pathogenic variants in newly identified NDD genes enabled us to provide a molecular diagnosis to 14 patients and their close relatives and caregivers. This underlines the relevance of re-evaluation of existing exome data on a regular basis to improve the diagnostic yield and serve the needs of our patients. En ligne : https://dx.doi.org/10.1186/s11689-019-9270-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Children with facial paralysis due to Moebius syndrome exhibit reduced autonomic modulation during emotion processing / E. DE STEFANI in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 12 p. Titre : Children with facial paralysis due to Moebius syndrome exhibit reduced autonomic modulation during emotion processing Type de document : Texte imprimé et/ou numérique Auteurs : E. DE STEFANI, Auteur ; M. ARDIZZI, Auteur ; Y. NICOLINI, Auteur ; M. BELLUARDO, Auteur ; A. BARBOT, Auteur ; C. BERTOLINI, Auteur ; G. GAROFALO, Auteur ; B. BIANCHI, Auteur ; G. COUDE, Auteur ; L. MURRAY, Auteur ; P. F. FERRARI, Auteur Article en page(s) : 12 p. Langues : Anglais (eng) Mots-clés : Autonomic nervous system  Emotion recognition  Facial expressions  Moebius children  Respiratory sinus arrhythmia  Thermal infrared imaging Index. décimale : PER Périodiques Résumé : BACKGROUND: Facial mimicry is crucial in the recognition of others' emotional state. Thus, the observation of others' facial expressions activates the same neural representation of that affective state in the observer, along with related autonomic and somatic responses. What happens, therefore, when someone cannot mimic others' facial expressions? METHODS: We investigated whether psychophysiological emotional responses to others' facial expressions were impaired in 13 children (9 years) with Moebius syndrome (MBS), an extremely rare neurological disorder (1/250,000 live births) characterized by congenital facial paralysis. We inspected autonomic responses and vagal regulation through facial cutaneous thermal variations and by the computation of respiratory sinus arrhythmia (RSA). These parameters provide measures of emotional arousal and show the autonomic adaptation to others' social cues. Physiological responses in children with MBS were recorded during dynamic facial expression observation and were compared to those of a control group (16 non-affected children, 9 years). RESULTS: There were significant group effects on thermal patterns and RSA, with lower values in children with MBS. We also observed a mild deficit in emotion recognition in these patients. CONCLUSION: Results support "embodied" theory, whereby the congenital inability to produce facial expressions induces alterations in the processing of facial expression of emotions. Such alterations may constitute a risk for emotion dysregulation. En ligne : https://dx.doi.org/10.1186/s11689-019-9272-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Children with facial paralysis due to Moebius syndrome exhibit reduced autonomic modulation during emotion processing [Texte imprimé et/ou numérique] / E. DE STEFANI, Auteur ; M. ARDIZZI, Auteur ; Y. NICOLINI, Auteur ; M. BELLUARDO, Auteur ; A. BARBOT, Auteur ; C. BERTOLINI, Auteur ; G. GAROFALO, Auteur ; B. BIANCHI, Auteur ; G. COUDE, Auteur ; L. MURRAY, Auteur ; P. F. FERRARI, Auteur . - 12 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 12 p. Mots-clés : Autonomic nervous system  Emotion recognition  Facial expressions  Moebius children  Respiratory sinus arrhythmia  Thermal infrared imaging Index. décimale : PER Périodiques Résumé : BACKGROUND: Facial mimicry is crucial in the recognition of others' emotional state. Thus, the observation of others' facial expressions activates the same neural representation of that affective state in the observer, along with related autonomic and somatic responses. What happens, therefore, when someone cannot mimic others' facial expressions? METHODS: We investigated whether psychophysiological emotional responses to others' facial expressions were impaired in 13 children (9 years) with Moebius syndrome (MBS), an extremely rare neurological disorder (1/250,000 live births) characterized by congenital facial paralysis. We inspected autonomic responses and vagal regulation through facial cutaneous thermal variations and by the computation of respiratory sinus arrhythmia (RSA). These parameters provide measures of emotional arousal and show the autonomic adaptation to others' social cues. Physiological responses in children with MBS were recorded during dynamic facial expression observation and were compared to those of a control group (16 non-affected children, 9 years). RESULTS: There were significant group effects on thermal patterns and RSA, with lower values in children with MBS. We also observed a mild deficit in emotion recognition in these patients. CONCLUSION: Results support "embodied" theory, whereby the congenital inability to produce facial expressions induces alterations in the processing of facial expression of emotions. Such alterations may constitute a risk for emotion dysregulation. En ligne : https://dx.doi.org/10.1186/s11689-019-9272-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

A Brazilian cohort of individuals with Phelan-McDermid syndrome: genotype-phenotype correlation and identification of an atypical case / C. I. SAMOGY-COSTA in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 13 p. Titre : A Brazilian cohort of individuals with Phelan-McDermid syndrome: genotype-phenotype correlation and identification of an atypical case Type de document : Texte imprimé et/ou numérique Auteurs : C. I. SAMOGY-COSTA, Auteur ; E. VARELLA-BRANCO, Auteur ; F. MONFARDINI, Auteur ; H. FERRAZ, Auteur ; R. A. FOCK, Auteur ; R. H. A. BARBOSA, Auteur ; A. L. S. PESSOA, Auteur ; A. B. A. PEREZ, Auteur ; N. LOURENCO, Auteur ; M. VIBRANOVSKI, Auteur ; A. KREPISCHI, Auteur ; C. ROSENBERG, Auteur ; M. R. PASSOS-BUENO, Auteur Article en page(s) : 13 p. Langues : Anglais (eng) Mots-clés : 22q13.3 deletion syndrome  Autism spectrum disorder  Phelan-McDermid syndrome  Shank3 Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is a rare genetic disorder characterized by global developmental delay, intellectual disability (ID), autism spectrum disorder (ASD), and mild dysmorphisms associated with several comorbidities caused by SHANK3 loss-of-function mutations. Although SHANK3 haploinsufficiency has been associated with the major neurological symptoms of PMS, it cannot explain the clinical variability seen among individuals. Our goals were to characterize a Brazilian cohort of PMS individuals, explore the genotype-phenotype correlation underlying this syndrome, and describe an atypical individual with mild phenotype. METHODOLOGY: A total of 34 PMS individuals were clinically and genetically evaluated. Data were obtained by a questionnaire answered by parents, and dysmorphic features were assessed via photographic evaluation. We analyzed 22q13.3 deletions and other potentially pathogenic copy number variants (CNVs) and also performed genotype-phenotype correlation analysis to determine whether comorbidities, speech status, and ASD correlate to deletion size. Finally, a Brazilian cohort of 829 ASD individuals and another independent cohort of 2297 ID individuals was used to determine the frequency of PMS in these disorders. RESULTS: Our data showed that 21% (6/29) of the PMS individuals presented an additional rare CNV, which may contribute to clinical variability in PMS. Increased pain tolerance (80%), hypotonia (85%), and sparse eyebrows (80%) were prominent clinical features. An atypical case diagnosed with PMS at 18 years old and IQ within the normal range is here described. Among Brazilian ASD or ID individuals referred to CNV analyses, the frequency of 22q13.3 deletion was 0.6% (5/829) and 0.61% (15/2297), respectively. Finally, renal abnormalities, lymphedema, and language impairment were found to be positively associated with deletion sizes, and the minimum deletion to cause these abnormalities is here suggested. CONCLUSIONS: This is the first work describing a cohort of Brazilian individuals with PMS. Our results confirm the impact of 22q13 deletions on ASD and several comorbidities, such as hypotonia. The estimation of a minimal deletion size for developing lymphedema and renal problem can assist prediction of prognosis in PMS individuals, particularly those diagnosed in early infancy. We also identified one atypical individual carrying SHANK3 deletion, suggesting that resilience to such mutations occurs. This case expands the clinical spectrum of variability in PMS and opens perspectives to identify protective mechanisms that can minimize the severity of this condition. En ligne : https://dx.doi.org/10.1186/s11689-019-9273-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] A Brazilian cohort of individuals with Phelan-McDermid syndrome: genotype-phenotype correlation and identification of an atypical case [Texte imprimé et/ou numérique] / C. I. SAMOGY-COSTA, Auteur ; E. VARELLA-BRANCO, Auteur ; F. MONFARDINI, Auteur ; H. FERRAZ, Auteur ; R. A. FOCK, Auteur ; R. H. A. BARBOSA, Auteur ; A. L. S. PESSOA, Auteur ; A. B. A. PEREZ, Auteur ; N. LOURENCO, Auteur ; M. VIBRANOVSKI, Auteur ; A. KREPISCHI, Auteur ; C. ROSENBERG, Auteur ; M. R. PASSOS-BUENO, Auteur . - 13 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 13 p. Mots-clés : 22q13.3 deletion syndrome  Autism spectrum disorder  Phelan-McDermid syndrome  Shank3 Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is a rare genetic disorder characterized by global developmental delay, intellectual disability (ID), autism spectrum disorder (ASD), and mild dysmorphisms associated with several comorbidities caused by SHANK3 loss-of-function mutations. Although SHANK3 haploinsufficiency has been associated with the major neurological symptoms of PMS, it cannot explain the clinical variability seen among individuals. Our goals were to characterize a Brazilian cohort of PMS individuals, explore the genotype-phenotype correlation underlying this syndrome, and describe an atypical individual with mild phenotype. METHODOLOGY: A total of 34 PMS individuals were clinically and genetically evaluated. Data were obtained by a questionnaire answered by parents, and dysmorphic features were assessed via photographic evaluation. We analyzed 22q13.3 deletions and other potentially pathogenic copy number variants (CNVs) and also performed genotype-phenotype correlation analysis to determine whether comorbidities, speech status, and ASD correlate to deletion size. Finally, a Brazilian cohort of 829 ASD individuals and another independent cohort of 2297 ID individuals was used to determine the frequency of PMS in these disorders. RESULTS: Our data showed that 21% (6/29) of the PMS individuals presented an additional rare CNV, which may contribute to clinical variability in PMS. Increased pain tolerance (80%), hypotonia (85%), and sparse eyebrows (80%) were prominent clinical features. An atypical case diagnosed with PMS at 18 years old and IQ within the normal range is here described. Among Brazilian ASD or ID individuals referred to CNV analyses, the frequency of 22q13.3 deletion was 0.6% (5/829) and 0.61% (15/2297), respectively. Finally, renal abnormalities, lymphedema, and language impairment were found to be positively associated with deletion sizes, and the minimum deletion to cause these abnormalities is here suggested. CONCLUSIONS: This is the first work describing a cohort of Brazilian individuals with PMS. Our results confirm the impact of 22q13 deletions on ASD and several comorbidities, such as hypotonia. The estimation of a minimal deletion size for developing lymphedema and renal problem can assist prediction of prognosis in PMS individuals, particularly those diagnosed in early infancy. We also identified one atypical individual carrying SHANK3 deletion, suggesting that resilience to such mutations occurs. This case expands the clinical spectrum of variability in PMS and opens perspectives to identify protective mechanisms that can minimize the severity of this condition. En ligne : https://dx.doi.org/10.1186/s11689-019-9273-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Infant regulatory function acts as a protective factor for later traits of autism spectrum disorder and attention deficit/hyperactivity disorder but not callous unemotional traits / Rachael BEDFORD in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 14 p. Titre : Infant regulatory function acts as a protective factor for later traits of autism spectrum disorder and attention deficit/hyperactivity disorder but not callous unemotional traits Type de document : Texte imprimé et/ou numérique Auteurs : Rachael BEDFORD, Auteur ; T. GLIGA, Auteur ; A. HENDRY, Auteur ; E. J. H. JONES, Auteur ; G. PASCO, Auteur ; Tony CHARMAN, Auteur ; M. H. JOHNSON, Auteur ; A. PICKLES, Auteur Article en page(s) : 14 p. Langues : Anglais (eng) Mots-clés : Attention deficit/hyperactivity disorder  Autism spectrum disorder  Callous unemotional traits  Executive function  Infants at risk  Regulatory function Index. décimale : PER Périodiques Résumé : BACKGROUND: Reduced executive functions (EF) are commonly associated with developmental conditions (e.g., autism spectrum disorder, ASD; attention deficit/hyperactivity disorder, ADHD), although EF seems to be typical in children with callous unemotional (CU) traits. Regulatory function (RF) is a proposed infant precursor that maps on onto factors driving later EF. Here, we first test whether RF is specifically and negatively associated with ASD and ADHD traits, but not CU traits. Second, we test whether RF can act as a protective factor, by moderating the association between infant markers and subsequent ASD and ADHD traits. METHODS: Participants were 79 infants at high (N = 42) and low (N = 37) familial risk for ASD. Data come from the 14-month infant visit (Autism Observational Scale for Infants; AOSI; activity level and RF from the Infant Behavior Questionnaire; IBQ) and the 7-year visit (ASD traits: Social Responsiveness Scale, SRS; ADHD traits: Conners 3, CU traits: Inventory of Callous Unemotional Traits). RESULTS: Infant RF was negatively associated with later traits of ASD (B = - 0.5, p = 0.01) and ADHD inattention (B = - 0.24, p = 0.02) but not hyperactivity (B = - 0.25, p = 0.10) or CU traits (B = 0.02, p = 0.86). RF moderated the association between infant AOSI score and ASD traits, with a significant effect in those with low RF (B = 0.10, p = 0.006), not high RF (B = 0.01, p = 0.78). Similarly, for ADHD, infant activity level was associated with later ADHD inattention in those with low (B = 0.17, p = 0.04) but not high RF (B = 0.07, p = 0.48). For ADHD hyperactivity symptoms, activity level was predictive at both high and low levels of RF. CONCLUSIONS: Strong RF may allow children to compensate for other atypicalities, thus attenuating the association between infant markers and later disorder traits. Whilst infant RF was associated with both ASD and ADHD inattention traits, there was no association with ADHD hyperactivity or CU traits. This suggests that any protective effect may not be universal and emphasises the need for a better understanding of the underlying moderating mechanisms. En ligne : https://dx.doi.org/10.1186/s11689-019-9274-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Infant regulatory function acts as a protective factor for later traits of autism spectrum disorder and attention deficit/hyperactivity disorder but not callous unemotional traits [Texte imprimé et/ou numérique] / Rachael BEDFORD, Auteur ; T. GLIGA, Auteur ; A. HENDRY, Auteur ; E. J. H. JONES, Auteur ; G. PASCO, Auteur ; Tony CHARMAN, Auteur ; M. H. JOHNSON, Auteur ; A. PICKLES, Auteur . - 14 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 14 p. Mots-clés : Attention deficit/hyperactivity disorder  Autism spectrum disorder  Callous unemotional traits  Executive function  Infants at risk  Regulatory function Index. décimale : PER Périodiques Résumé : BACKGROUND: Reduced executive functions (EF) are commonly associated with developmental conditions (e.g., autism spectrum disorder, ASD; attention deficit/hyperactivity disorder, ADHD), although EF seems to be typical in children with callous unemotional (CU) traits. Regulatory function (RF) is a proposed infant precursor that maps on onto factors driving later EF. Here, we first test whether RF is specifically and negatively associated with ASD and ADHD traits, but not CU traits. Second, we test whether RF can act as a protective factor, by moderating the association between infant markers and subsequent ASD and ADHD traits. METHODS: Participants were 79 infants at high (N = 42) and low (N = 37) familial risk for ASD. Data come from the 14-month infant visit (Autism Observational Scale for Infants; AOSI; activity level and RF from the Infant Behavior Questionnaire; IBQ) and the 7-year visit (ASD traits: Social Responsiveness Scale, SRS; ADHD traits: Conners 3, CU traits: Inventory of Callous Unemotional Traits). RESULTS: Infant RF was negatively associated with later traits of ASD (B = - 0.5, p = 0.01) and ADHD inattention (B = - 0.24, p = 0.02) but not hyperactivity (B = - 0.25, p = 0.10) or CU traits (B = 0.02, p = 0.86). RF moderated the association between infant AOSI score and ASD traits, with a significant effect in those with low RF (B = 0.10, p = 0.006), not high RF (B = 0.01, p = 0.78). Similarly, for ADHD, infant activity level was associated with later ADHD inattention in those with low (B = 0.17, p = 0.04) but not high RF (B = 0.07, p = 0.48). For ADHD hyperactivity symptoms, activity level was predictive at both high and low levels of RF. CONCLUSIONS: Strong RF may allow children to compensate for other atypicalities, thus attenuating the association between infant markers and later disorder traits. Whilst infant RF was associated with both ASD and ADHD inattention traits, there was no association with ADHD hyperactivity or CU traits. This suggests that any protective effect may not be universal and emphasises the need for a better understanding of the underlying moderating mechanisms. En ligne : https://dx.doi.org/10.1186/s11689-019-9274-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Electroencephalographic spectral power as a marker of cortical function and disease severity in girls with Rett syndrome / K. J. ROCHE in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 15 p. Titre : Electroencephalographic spectral power as a marker of cortical function and disease severity in girls with Rett syndrome Type de document : Texte imprimé et/ou numérique Auteurs : K. J. ROCHE, Auteur ; J. J. LEBLANC, Auteur ; A. R. LEVIN, Auteur ; H. M. O'LEARY, Auteur ; L. M. BACZEWSKI, Auteur ; C. A. NELSON, Auteur Article en page(s) : 15 p. Langues : Anglais (eng) Mots-clés : Biomarker  Eeg  Electroencephalography  Electrophysiology  Rett syndrome  Spectral power Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett syndrome is a neurodevelopmental disorder caused by a mutation in the X-linked MECP2 gene. Individuals with Rett syndrome typically develop normally until around 18 months of age before undergoing a developmental regression, and the disorder can lead to cognitive, motor, sensory, and autonomic dysfunction. Understanding the mechanism of developmental regression represents a unique challenge when viewed through a neuroscience lens. Are circuits that were previously established erased, and are new ones built to supplant old ones? One way to examine circuit-level changes is with the use of electroencephalography (EEG). Previous studies of the EEG in individuals with Rett syndrome have focused on morphological characteristics, but few have explored spectral power, including power as an index of brain function or disease severity. This study sought to determine if EEG power differs in girls with Rett syndrome and typically developing girls and among girls with Rett syndrome based on various clinical characteristics in order to better understand neural connectivity and cortical organization in individuals with this disorder. METHODS: Resting state EEG data were acquired from girls with Rett syndrome (n = 57) and typically developing children without Rett syndrome (n = 37). Clinical data were also collected for girls with Rett syndrome. EEG power across several brain regions in numerous frequency bands was then compared between girls with Rett syndrome and typically developing children and power in girls with Rett syndrome was compared based on these clinical measures. 1/f slope was also compared between groups. RESULTS: Girls with Rett syndrome demonstrate significantly lower power in the middle frequency bands across multiple brain regions. Additionally, girls with Rett syndrome that are postregression demonstrate significantly higher power in the lower frequency delta and theta bands and a significantly more negative slope of the power spectrum. Increased power in these bands, as well as a more negative 1/f slope, trended with lower cognitive assessment scores. CONCLUSIONS: Increased power in lower frequency bands is consistent with previous studies demonstrating a "slowing" of the background EEG in Rett syndrome. This increase, particularly in the delta band, could represent abnormal cortical inhibition due to dysfunctional GABAergic signaling and could potentially be used as a marker of severity due to associations with more severe Rett syndrome phenotypes. En ligne : https://dx.doi.org/10.1186/s11689-019-9275-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Electroencephalographic spectral power as a marker of cortical function and disease severity in girls with Rett syndrome [Texte imprimé et/ou numérique] / K. J. ROCHE, Auteur ; J. J. LEBLANC, Auteur ; A. R. LEVIN, Auteur ; H. M. O'LEARY, Auteur ; L. M. BACZEWSKI, Auteur ; C. A. NELSON, Auteur . - 15 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 15 p. Mots-clés : Biomarker  Eeg  Electroencephalography  Electrophysiology  Rett syndrome  Spectral power Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett syndrome is a neurodevelopmental disorder caused by a mutation in the X-linked MECP2 gene. Individuals with Rett syndrome typically develop normally until around 18 months of age before undergoing a developmental regression, and the disorder can lead to cognitive, motor, sensory, and autonomic dysfunction. Understanding the mechanism of developmental regression represents a unique challenge when viewed through a neuroscience lens. Are circuits that were previously established erased, and are new ones built to supplant old ones? One way to examine circuit-level changes is with the use of electroencephalography (EEG). Previous studies of the EEG in individuals with Rett syndrome have focused on morphological characteristics, but few have explored spectral power, including power as an index of brain function or disease severity. This study sought to determine if EEG power differs in girls with Rett syndrome and typically developing girls and among girls with Rett syndrome based on various clinical characteristics in order to better understand neural connectivity and cortical organization in individuals with this disorder. METHODS: Resting state EEG data were acquired from girls with Rett syndrome (n = 57) and typically developing children without Rett syndrome (n = 37). Clinical data were also collected for girls with Rett syndrome. EEG power across several brain regions in numerous frequency bands was then compared between girls with Rett syndrome and typically developing children and power in girls with Rett syndrome was compared based on these clinical measures. 1/f slope was also compared between groups. RESULTS: Girls with Rett syndrome demonstrate significantly lower power in the middle frequency bands across multiple brain regions. Additionally, girls with Rett syndrome that are postregression demonstrate significantly higher power in the lower frequency delta and theta bands and a significantly more negative slope of the power spectrum. Increased power in these bands, as well as a more negative 1/f slope, trended with lower cognitive assessment scores. CONCLUSIONS: Increased power in lower frequency bands is consistent with previous studies demonstrating a "slowing" of the background EEG in Rett syndrome. This increase, particularly in the delta band, could represent abnormal cortical inhibition due to dysfunctional GABAergic signaling and could potentially be used as a marker of severity due to associations with more severe Rett syndrome phenotypes. En ligne : https://dx.doi.org/10.1186/s11689-019-9275-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

A phase 1/2, open-label assessment of the safety, tolerability, and efficacy of transdermal cannabidiol (ZYN002) for the treatment of pediatric fragile X syndrome / H. HEUSSLER in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 16 p. Titre : A phase 1/2, open-label assessment of the safety, tolerability, and efficacy of transdermal cannabidiol (ZYN002) for the treatment of pediatric fragile X syndrome Type de document : Texte imprimé et/ou numérique Auteurs : H. HEUSSLER, Auteur ; J. COHEN, Auteur ; N. SILOVE, Auteur ; N. TICH, Auteur ; M. O. BONN-MILLER, Auteur ; W. DU, Auteur ; C. O'NEILL, Auteur ; T. SEBREE, Auteur Article en page(s) : 16 p. Langues : Anglais (eng) Mots-clés : Cannabidiol  Fragile X  Pediatric  Transdermal  Zyn002  Zynerba Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is characterized by a range of developmental, neuropsychiatric, and behavioral symptoms that cause significant impairment in those with the disorder. Cannabidiol (CBD) holds promise as a potential treatment for FXS symptoms due to its safety profile and positive effects on a number of emotional and behavioral symptoms associated with FXS. The aim of the current study was to evaluate the safety, tolerability, and initial efficacy of ZYN002, a transdermal CBD gel, in a pediatric population with FXS. METHODS: Twenty children and adolescents (aged 6-17 years) with a diagnosis of FXS (confirmed through molecular documentation of FMR1 full mutation) were enrolled in an open-label, multi-site, trial of ZYN002. Transdermal CBD gel was administered twice daily for 12 weeks, titrated from 50 mg to a maximum daily dose of 250 mg. The primary efficacy endpoint was change from screening to week 12 on the Anxiety, Depression, and Mood Scale (ADAMS). Secondary endpoint measures included the Aberrant Behavior Checklist-Community for FXS (ABC-CFXS), Pediatric Anxiety Rating Scale (PARS-R), Pediatric Quality of Life Inventory (PedsQL), three Visual Analogue Scales (VAS), and the Clinical Global Impression Scale-Severity (CGI-S) and Improvement (CGI-I). RESULTS: The majority of treatment-emergent AEs (reported by 85% of participants) were mild in severity (70%), and no serious adverse events were reported. There was a statistically significant reduction in ADAMS total score from screening to week 12 and significant reductions on nearly all other secondary endpoints, including all ADAMS subscales (except depressed mood), all ABC-CFXS subscale scores (e.g., social avoidance, irritability), PARS-R total severity score, and PedsQL total score. CONCLUSIONS: ZYN002 was well tolerated and produced clinically meaningful reductions in anxiety and behavioral symptoms in children and adolescents with FXS. These findings support further study of ZYN002 in a randomized, well-controlled trial for the treatment of behavioral symptoms of FXS. TRIAL REGISTRATION: ANZCTR, ACTRN12617000150347 Registered 27 January 2017. En ligne : https://dx.doi.org/10.1186/s11689-019-9277-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] A phase 1/2, open-label assessment of the safety, tolerability, and efficacy of transdermal cannabidiol (ZYN002) for the treatment of pediatric fragile X syndrome [Texte imprimé et/ou numérique] / H. HEUSSLER, Auteur ; J. COHEN, Auteur ; N. SILOVE, Auteur ; N. TICH, Auteur ; M. O. BONN-MILLER, Auteur ; W. DU, Auteur ; C. O'NEILL, Auteur ; T. SEBREE, Auteur . - 16 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 16 p. Mots-clés : Cannabidiol  Fragile X  Pediatric  Transdermal  Zyn002  Zynerba Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is characterized by a range of developmental, neuropsychiatric, and behavioral symptoms that cause significant impairment in those with the disorder. Cannabidiol (CBD) holds promise as a potential treatment for FXS symptoms due to its safety profile and positive effects on a number of emotional and behavioral symptoms associated with FXS. The aim of the current study was to evaluate the safety, tolerability, and initial efficacy of ZYN002, a transdermal CBD gel, in a pediatric population with FXS. METHODS: Twenty children and adolescents (aged 6-17 years) with a diagnosis of FXS (confirmed through molecular documentation of FMR1 full mutation) were enrolled in an open-label, multi-site, trial of ZYN002. Transdermal CBD gel was administered twice daily for 12 weeks, titrated from 50 mg to a maximum daily dose of 250 mg. The primary efficacy endpoint was change from screening to week 12 on the Anxiety, Depression, and Mood Scale (ADAMS). Secondary endpoint measures included the Aberrant Behavior Checklist-Community for FXS (ABC-CFXS), Pediatric Anxiety Rating Scale (PARS-R), Pediatric Quality of Life Inventory (PedsQL), three Visual Analogue Scales (VAS), and the Clinical Global Impression Scale-Severity (CGI-S) and Improvement (CGI-I). RESULTS: The majority of treatment-emergent AEs (reported by 85% of participants) were mild in severity (70%), and no serious adverse events were reported. There was a statistically significant reduction in ADAMS total score from screening to week 12 and significant reductions on nearly all other secondary endpoints, including all ADAMS subscales (except depressed mood), all ABC-CFXS subscale scores (e.g., social avoidance, irritability), PARS-R total severity score, and PedsQL total score. CONCLUSIONS: ZYN002 was well tolerated and produced clinically meaningful reductions in anxiety and behavioral symptoms in children and adolescents with FXS. These findings support further study of ZYN002 in a randomized, well-controlled trial for the treatment of behavioral symptoms of FXS. TRIAL REGISTRATION: ANZCTR, ACTRN12617000150347 Registered 27 January 2017. En ligne : https://dx.doi.org/10.1186/s11689-019-9277-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

STXBP1-associated neurodevelopmental disorder: a comparative study of behavioural characteristics / S. O'BRIEN in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 17 p. Titre : STXBP1-associated neurodevelopmental disorder: a comparative study of behavioural characteristics Type de document : Texte imprimé et/ou numérique Auteurs : S. O'BRIEN, Auteur ; E. NG-CORDELL, Auteur ; Duncan E. ASTLE, Auteur ; G. SCERIF, Auteur ; K. BAKER, Auteur Article en page(s) : 17 p. Langues : Anglais (eng) Mots-clés : Epilepsy  Intellectual disability  Language  Stxbp1  Social Index. décimale : PER Périodiques Résumé : BACKGROUND: De novo loss of function mutations in STXBP1 are a relatively common cause of epilepsy and intellectual disability (ID). However, little is known about the types and severities of behavioural features associated with this genetic diagnosis. METHODS: To address this, we collected systematic phenotyping data encompassing neurological, developmental, and behavioural characteristics. Participants were 14 individuals with STXBP1-associated neurodevelopmental disorder, ascertained from clinical genetics and neurology services UK-wide. Data was collected via standardised questionnaires administered to parents at home, supplemented by researcher observations. To isolate discriminating phenotypes, the STXBP1 group was compared to 33 individuals with pathogenic mutations in other ID-associated genes (ID group). To account for the potential impact of global cognitive impairment, a secondary comparison was made to an ability-matched subset of the ID group (low-ability ID group). RESULTS: The STXBP1 group demonstrated impairments across all assessed domains. In comparison to the ID group, the STXBP1 group had more severe global adaptive impairments, fine motor difficulties, and hyperactivity. In comparison to the low-ability ID group, severity of receptive language and social impairments discriminated the STXBP1 group. A striking feature of the STXBP1 group, with reference to both comparison groups, was preservation of social motivation. CONCLUSIONS: De novo mutations in STXBP1 are associated with complex and variable neurodevelopmental impairments. Consistent features, which discriminate this disorder from other monogenic causes of ID, are severe language impairment and difficulties managing social interactions, despite strong social motivation. Future work could explore the physiological mechanisms linking motor, speech, and social development in this disorder. Understanding the developmental emergence of behavioural characteristics can help to focus clinical assessment and management after genetic diagnosis, with the long-term aim of improving outcomes for patients and families. En ligne : https://dx.doi.org/10.1186/s11689-019-9278-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] STXBP1-associated neurodevelopmental disorder: a comparative study of behavioural characteristics [Texte imprimé et/ou numérique] / S. O'BRIEN, Auteur ; E. NG-CORDELL, Auteur ; Duncan E. ASTLE, Auteur ; G. SCERIF, Auteur ; K. BAKER, Auteur . - 17 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 17 p. Mots-clés : Epilepsy  Intellectual disability  Language  Stxbp1  Social Index. décimale : PER Périodiques Résumé : BACKGROUND: De novo loss of function mutations in STXBP1 are a relatively common cause of epilepsy and intellectual disability (ID). However, little is known about the types and severities of behavioural features associated with this genetic diagnosis. METHODS: To address this, we collected systematic phenotyping data encompassing neurological, developmental, and behavioural characteristics. Participants were 14 individuals with STXBP1-associated neurodevelopmental disorder, ascertained from clinical genetics and neurology services UK-wide. Data was collected via standardised questionnaires administered to parents at home, supplemented by researcher observations. To isolate discriminating phenotypes, the STXBP1 group was compared to 33 individuals with pathogenic mutations in other ID-associated genes (ID group). To account for the potential impact of global cognitive impairment, a secondary comparison was made to an ability-matched subset of the ID group (low-ability ID group). RESULTS: The STXBP1 group demonstrated impairments across all assessed domains. In comparison to the ID group, the STXBP1 group had more severe global adaptive impairments, fine motor difficulties, and hyperactivity. In comparison to the low-ability ID group, severity of receptive language and social impairments discriminated the STXBP1 group. A striking feature of the STXBP1 group, with reference to both comparison groups, was preservation of social motivation. CONCLUSIONS: De novo mutations in STXBP1 are associated with complex and variable neurodevelopmental impairments. Consistent features, which discriminate this disorder from other monogenic causes of ID, are severe language impairment and difficulties managing social interactions, despite strong social motivation. Future work could explore the physiological mechanisms linking motor, speech, and social development in this disorder. Understanding the developmental emergence of behavioural characteristics can help to focus clinical assessment and management after genetic diagnosis, with the long-term aim of improving outcomes for patients and families. En ligne : https://dx.doi.org/10.1186/s11689-019-9278-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Phenotypic characterization of individuals with SYNGAP1 pathogenic variants reveals a potential correlation between posterior dominant rhythm and developmental progression / A. JIMENEZ-GOMEZ in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 18 p. Titre : Phenotypic characterization of individuals with SYNGAP1 pathogenic variants reveals a potential correlation between posterior dominant rhythm and developmental progression Type de document : Texte imprimé et/ou numérique Auteurs : A. JIMENEZ-GOMEZ, Auteur ; S. NIU, Auteur ; F. ANDUJAR-PEREZ, Auteur ; E. A. MCQUADE, Auteur ; A. BALASA, Auteur ; D. HUSS, Auteur ; R. COORG, Auteur ; M. QUACH, Auteur ; S. VINSON, Auteur ; S. RISEN, Auteur ; J. L. HOLDER, Auteur Article en page(s) : 18 p. Langues : Anglais (eng) Mots-clés : Autism  Electroencephalogram  Neurodevelopment  Posterior dominant rhythm  Syngap1 Index. décimale : PER Périodiques Résumé : BACKGROUND: The SYNGAP1 gene encodes for a small GTPase-regulating protein critical to dendritic spine maturation and synaptic plasticity. Mutations have recently been identified to cause a breadth of neurodevelopmental disorders including autism, intellectual disability, and epilepsy. The purpose of this work is to define the phenotypic spectrum of SYNGAP1 gene mutations and identify potential biomarkers of clinical severity and developmental progression. METHODS: A retrospective clinical data analysis of individuals with SYNGAP1 mutations was conducted. Data included genetic diagnosis, clinical history and examinations, neurophysiologic data, neuroimaging, and serial neurodevelopmental/behavioral assessments. All patients were seen longitudinally within a 6-year period; data analysis was completed on June 30, 2018. Records for all individuals diagnosed with deleterious SYNGAP1 variants (by clinical sequencing or exome sequencing panels) were reviewed. RESULTS: Fifteen individuals (53% male) with seventeen unique SYNGAP1 mutations are reported. Mean age at genetic diagnosis was 65.9 months (28-174 months). All individuals had epilepsy, with atypical absence seizures being the most common semiology (60%). EEG abnormalities included intermittent rhythmic delta activity (60%), slow or absent posterior dominant rhythm (87%), and epileptiform activity (93%), with generalized discharges being more common than focal. Neuroimaging revealed nonspecific abnormalities (53%). Neurodevelopmental evaluation revealed impairment in all individuals, with gross motor function being the least affected. Autism spectrum disorder was diagnosed in 73% and aggression in 60% of cases. Analysis of biomarkers revealed a trend toward a moderate positive correlation between visual-perceptual/fine motor/adaptive skills and language development, with posterior dominant rhythm on electroencephalogram (EEG), independent of age. No other neurophysiology-development associations or correlations were identified. CONCLUSIONS: A broad spectrum of neurologic and neurodevelopmental features are found with pathogenic variants of SYNGAP1. An abnormal posterior dominant rhythm on EEG correlated with abnormal developmental progression, providing a possible prognostic biomarker. En ligne : https://dx.doi.org/10.1186/s11689-019-9276-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Phenotypic characterization of individuals with SYNGAP1 pathogenic variants reveals a potential correlation between posterior dominant rhythm and developmental progression [Texte imprimé et/ou numérique] / A. JIMENEZ-GOMEZ, Auteur ; S. NIU, Auteur ; F. ANDUJAR-PEREZ, Auteur ; E. A. MCQUADE, Auteur ; A. BALASA, Auteur ; D. HUSS, Auteur ; R. COORG, Auteur ; M. QUACH, Auteur ; S. VINSON, Auteur ; S. RISEN, Auteur ; J. L. HOLDER, Auteur . - 18 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 18 p. Mots-clés : Autism  Electroencephalogram  Neurodevelopment  Posterior dominant rhythm  Syngap1 Index. décimale : PER Périodiques Résumé : BACKGROUND: The SYNGAP1 gene encodes for a small GTPase-regulating protein critical to dendritic spine maturation and synaptic plasticity. Mutations have recently been identified to cause a breadth of neurodevelopmental disorders including autism, intellectual disability, and epilepsy. The purpose of this work is to define the phenotypic spectrum of SYNGAP1 gene mutations and identify potential biomarkers of clinical severity and developmental progression. METHODS: A retrospective clinical data analysis of individuals with SYNGAP1 mutations was conducted. Data included genetic diagnosis, clinical history and examinations, neurophysiologic data, neuroimaging, and serial neurodevelopmental/behavioral assessments. All patients were seen longitudinally within a 6-year period; data analysis was completed on June 30, 2018. Records for all individuals diagnosed with deleterious SYNGAP1 variants (by clinical sequencing or exome sequencing panels) were reviewed. RESULTS: Fifteen individuals (53% male) with seventeen unique SYNGAP1 mutations are reported. Mean age at genetic diagnosis was 65.9 months (28-174 months). All individuals had epilepsy, with atypical absence seizures being the most common semiology (60%). EEG abnormalities included intermittent rhythmic delta activity (60%), slow or absent posterior dominant rhythm (87%), and epileptiform activity (93%), with generalized discharges being more common than focal. Neuroimaging revealed nonspecific abnormalities (53%). Neurodevelopmental evaluation revealed impairment in all individuals, with gross motor function being the least affected. Autism spectrum disorder was diagnosed in 73% and aggression in 60% of cases. Analysis of biomarkers revealed a trend toward a moderate positive correlation between visual-perceptual/fine motor/adaptive skills and language development, with posterior dominant rhythm on electroencephalogram (EEG), independent of age. No other neurophysiology-development associations or correlations were identified. CONCLUSIONS: A broad spectrum of neurologic and neurodevelopmental features are found with pathogenic variants of SYNGAP1. An abnormal posterior dominant rhythm on EEG correlated with abnormal developmental progression, providing a possible prognostic biomarker. En ligne : https://dx.doi.org/10.1186/s11689-019-9276-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Magnetoencephalographic (MEG) brain activity during a mental flexibility task suggests some shared neurobiology in children with neurodevelopmental disorders / A. MOGADAM in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 19 p. Titre : Magnetoencephalographic (MEG) brain activity during a mental flexibility task suggests some shared neurobiology in children with neurodevelopmental disorders Type de document : Texte imprimé et/ou numérique Auteurs : A. MOGADAM, Auteur ; A. E. KELLER, Auteur ; P. D. ARNOLD, Auteur ; Russell SCHACHAR, Auteur ; J. P. LERCH, Auteur ; Evdokia ANAGNOSTOU, Auteur ; Elizabeth W. PANG, Auteur Article en page(s) : 19 p. Langues : Anglais (eng) Mots-clés : Adhd  Asd  Corticostriatal projections  Executive function  Meg  Neurodevelopmental disorders  Ocd  Rbs-r  Set shifting  Tocs Index. décimale : PER Périodiques Résumé : BACKGROUND: Children with neurodevelopmental disorders (NDDs) exhibit a shared phenotype that involves executive dysfunctions including impairments in mental flexibility (MF). It is of interest to understand if this phenotype stems from some shared neurobiology. METHODS: To investigate this possibility, we used magnetoencephalography (MEG) neuroimaging to compare brain activity in children (n = 88; 8-15 years) with autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD), as they completed a set-shifting/mental flexibility task. RESULTS: Neuroimaging results revealed a similar parietal activation profile across the NDD, groups suggesting a link to their shared phenotype. Differences in frontal activity differentiated the three clinical groups. Brain-behaviour analyses showed a link with repetitive behaviours suggesting shared dysfunction in the associative loop of the corticostriatal system. CONCLUSION: Our study supports the notion that NDDs may exist along a complex phenotypic/biological continuum. All NDD groups showed a sustained parietal activity profile suggesting that they share a strong reliance on the posterior parietal cortices to complete the mental flexibility task; future studies could elucidate whether this is due to delayed brain development or compensatory functioning. The differences in frontal activity may play a role in differentiating the NDDs. The OCD group showed sustained prefrontal activity that may be reflective of hyperfrontality. The ASD group showed reduced frontal activation suggestive of frontal dysfunction and the ADHD group showed an extensive hypoactivity that included frontal and parietal regions. Brain-behaviour analyses showed a significant correlation with repetitive behaviours which may reflect dysfunction in the associative loop of the corticostriatal system, linked to inflexible behaviours. En ligne : https://dx.doi.org/10.1186/s11689-019-9280-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Magnetoencephalographic (MEG) brain activity during a mental flexibility task suggests some shared neurobiology in children with neurodevelopmental disorders [Texte imprimé et/ou numérique] / A. MOGADAM, Auteur ; A. E. KELLER, Auteur ; P. D. ARNOLD, Auteur ; Russell SCHACHAR, Auteur ; J. P. LERCH, Auteur ; Evdokia ANAGNOSTOU, Auteur ; Elizabeth W. PANG, Auteur . - 19 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 19 p. Mots-clés : Adhd  Asd  Corticostriatal projections  Executive function  Meg  Neurodevelopmental disorders  Ocd  Rbs-r  Set shifting  Tocs Index. décimale : PER Périodiques Résumé : BACKGROUND: Children with neurodevelopmental disorders (NDDs) exhibit a shared phenotype that involves executive dysfunctions including impairments in mental flexibility (MF). It is of interest to understand if this phenotype stems from some shared neurobiology. METHODS: To investigate this possibility, we used magnetoencephalography (MEG) neuroimaging to compare brain activity in children (n = 88; 8-15 years) with autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD), as they completed a set-shifting/mental flexibility task. RESULTS: Neuroimaging results revealed a similar parietal activation profile across the NDD, groups suggesting a link to their shared phenotype. Differences in frontal activity differentiated the three clinical groups. Brain-behaviour analyses showed a link with repetitive behaviours suggesting shared dysfunction in the associative loop of the corticostriatal system. CONCLUSION: Our study supports the notion that NDDs may exist along a complex phenotypic/biological continuum. All NDD groups showed a sustained parietal activity profile suggesting that they share a strong reliance on the posterior parietal cortices to complete the mental flexibility task; future studies could elucidate whether this is due to delayed brain development or compensatory functioning. The differences in frontal activity may play a role in differentiating the NDDs. The OCD group showed sustained prefrontal activity that may be reflective of hyperfrontality. The ASD group showed reduced frontal activation suggestive of frontal dysfunction and the ADHD group showed an extensive hypoactivity that included frontal and parietal regions. Brain-behaviour analyses showed a significant correlation with repetitive behaviours which may reflect dysfunction in the associative loop of the corticostriatal system, linked to inflexible behaviours. En ligne : https://dx.doi.org/10.1186/s11689-019-9280-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Assessing general cognitive and adaptive abilities in adults with Down syndrome: a systematic review / S. HAMBURG in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 20 p. Titre : Assessing general cognitive and adaptive abilities in adults with Down syndrome: a systematic review Type de document : Texte imprimé et/ou numérique Auteurs : S. HAMBURG, Auteur ; B. LOWE, Auteur ; C. M. STARTIN, Auteur ; C. PADILLA, Auteur ; A. COPPUS, Auteur ; W. SILVERMAN, Auteur ; J. FORTEA, Auteur ; S. ZAMAN, Auteur ; E. HEAD, Auteur ; B. L. HANDEN, Auteur ; I. LOTT, Auteur ; W. SONG, Auteur ; A. STRYDOM, Auteur Article en page(s) : 20 p. Langues : Anglais (eng) Mots-clés : Ab  Adaptive ability  Adaptive behaviour  Cognition  Down syndrome  General ability  Iq  Intelligence Index. décimale : PER Périodiques Résumé : BACKGROUND: Measures of general cognitive and adaptive ability in adults with Down syndrome (DS) used by previous studies vary substantially. This review summarises the different ability measures used previously, focusing on tests of intelligence quotient (IQ) and adaptive behaviour (AB), and where possible examines floor effects and differences between DS subpopulations. We aimed to use information regarding existing measures to provide recommendations for individual researchers and the DS research community. RESULTS: Nineteen studies reporting IQ test data met inclusion for this review, with 17 different IQ tests used. Twelve of these IQ tests were used in only one study while five were used in two different studies. Eleven studies reporting AB test data met inclusion for this review, with seven different AB tests used. The only AB scales to be used by more than one study were the Vineland Adaptive Behaviour Scale (VABS; used by three studies) and the Vineland Adaptive Behavior Scale 2nd Edition (VABS-II; used by two studies). A variety of additional factors were identified which make comparison of test scores between studies problematic, including different score types provided between studies (e.g. raw scores compared to age-equivalent scores) and different participant inclusion criteria (e.g. whether individuals with cognitive decline were excluded). Floor effects were common for IQ tests (particularly for standardised test scores). Data exists to suggest that floor effects may be minimised by the use of raw test scores rather than standardised test scores. Raw scores may, therefore, be particularly useful in longitudinal studies to track change in cognitive ability over time. CONCLUSIONS: Studies assessing general ability in adults with DS are likely to benefit from the use of both IQ and AB scales. The DS research community may benefit from the development of reporting standards for IQ and AB data, and from the sharing of raw study data enabling further in-depth investigation of issues highlighted by this review. En ligne : https://dx.doi.org/10.1186/s11689-019-9279-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Assessing general cognitive and adaptive abilities in adults with Down syndrome: a systematic review [Texte imprimé et/ou numérique] / S. HAMBURG, Auteur ; B. LOWE, Auteur ; C. M. STARTIN, Auteur ; C. PADILLA, Auteur ; A. COPPUS, Auteur ; W. SILVERMAN, Auteur ; J. FORTEA, Auteur ; S. ZAMAN, Auteur ; E. HEAD, Auteur ; B. L. HANDEN, Auteur ; I. LOTT, Auteur ; W. SONG, Auteur ; A. STRYDOM, Auteur . - 20 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 20 p. Mots-clés : Ab  Adaptive ability  Adaptive behaviour  Cognition  Down syndrome  General ability  Iq  Intelligence Index. décimale : PER Périodiques Résumé : BACKGROUND: Measures of general cognitive and adaptive ability in adults with Down syndrome (DS) used by previous studies vary substantially. This review summarises the different ability measures used previously, focusing on tests of intelligence quotient (IQ) and adaptive behaviour (AB), and where possible examines floor effects and differences between DS subpopulations. We aimed to use information regarding existing measures to provide recommendations for individual researchers and the DS research community. RESULTS: Nineteen studies reporting IQ test data met inclusion for this review, with 17 different IQ tests used. Twelve of these IQ tests were used in only one study while five were used in two different studies. Eleven studies reporting AB test data met inclusion for this review, with seven different AB tests used. The only AB scales to be used by more than one study were the Vineland Adaptive Behaviour Scale (VABS; used by three studies) and the Vineland Adaptive Behavior Scale 2nd Edition (VABS-II; used by two studies). A variety of additional factors were identified which make comparison of test scores between studies problematic, including different score types provided between studies (e.g. raw scores compared to age-equivalent scores) and different participant inclusion criteria (e.g. whether individuals with cognitive decline were excluded). Floor effects were common for IQ tests (particularly for standardised test scores). Data exists to suggest that floor effects may be minimised by the use of raw test scores rather than standardised test scores. Raw scores may, therefore, be particularly useful in longitudinal studies to track change in cognitive ability over time. CONCLUSIONS: Studies assessing general ability in adults with DS are likely to benefit from the use of both IQ and AB scales. The DS research community may benefit from the development of reporting standards for IQ and AB data, and from the sharing of raw study data enabling further in-depth investigation of issues highlighted by this review. En ligne : https://dx.doi.org/10.1186/s11689-019-9279-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Within-task variability on standardized language tests predicts autism spectrum disorder: a pilot study of the Response Dispersion Index / A. E. HARE-HARRIS in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 21 p. Titre : Within-task variability on standardized language tests predicts autism spectrum disorder: a pilot study of the Response Dispersion Index Type de document : Texte imprimé et/ou numérique Auteurs : A. E. HARE-HARRIS, Auteur ; M. W. MITCHEL, Auteur ; S. M. MYERS, Auteur ; A. D. MITCHEL, Auteur ; B. R. KING, Auteur ; B. G. RUOCCO, Auteur ; C. L. MARTIN, Auteur ; J. F. FLAX, Auteur ; L. M. BRZUSTOWICZ, Auteur Article en page(s) : 21 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Developmental difference  Intra-subtest scatter  Language impairment Index. décimale : PER Périodiques Résumé : BACKGROUND: Qualitatively atypical language development characterized by non-sequential skill acquisition within a developmental domain, which has been called developmental deviance or difference, is a common characteristic of autism spectrum disorder (ASD). We developed the Response Dispersion Index (RDI), a measure of this phenomenon based on intra-subtest scatter of item responses on standardized psychometric assessments, to assess the within-task variability among individuals with language impairment (LI) and/or ASD. METHODS: Standard clinical assessments of language were administered to 502 individuals from the New Jersey Language and Autism Genetics Study (NJLAGS) cohort. Participants were divided into four diagnostic groups: unaffected, ASD-only, LI-only, and ASD + LI. For each language measure, RDI was defined as the product of the total number of test items and the sum of the weight (based on item difficulty) of test items missed. Group differences in RDI were assessed, and the relationship between RDI and ASD diagnosis among individuals with LI was investigated for each language assessment. RESULTS: Although standard scores were unable to distinguish the LI-only and ASD/ASD + LI groups, the ASD/ASD + LI groups had higher RDI scores compared to LI-only group across all measures of expressive, pragmatic, and metalinguistic language. RDI was positively correlated with quantitative ASD traits across all subgroups and was an effective predictor of ASD diagnosis among individuals with LI. CONCLUSIONS: The RDI is an effective quantitative metric of developmental deviance/difference that correlates with ASD traits, supporting previous associations between ASD and non-sequential skill acquisition. The RDI can be adapted to other clinical measures to investigate the degree of difference that is not captured by standard performance summary scores. En ligne : https://dx.doi.org/10.1186/s11689-019-9283-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Within-task variability on standardized language tests predicts autism spectrum disorder: a pilot study of the Response Dispersion Index [Texte imprimé et/ou numérique] / A. E. HARE-HARRIS, Auteur ; M. W. MITCHEL, Auteur ; S. M. MYERS, Auteur ; A. D. MITCHEL, Auteur ; B. R. KING, Auteur ; B. G. RUOCCO, Auteur ; C. L. MARTIN, Auteur ; J. F. FLAX, Auteur ; L. M. BRZUSTOWICZ, Auteur . - 21 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 21 p. Mots-clés : Autism spectrum disorder  Developmental difference  Intra-subtest scatter  Language impairment Index. décimale : PER Périodiques Résumé : BACKGROUND: Qualitatively atypical language development characterized by non-sequential skill acquisition within a developmental domain, which has been called developmental deviance or difference, is a common characteristic of autism spectrum disorder (ASD). We developed the Response Dispersion Index (RDI), a measure of this phenomenon based on intra-subtest scatter of item responses on standardized psychometric assessments, to assess the within-task variability among individuals with language impairment (LI) and/or ASD. METHODS: Standard clinical assessments of language were administered to 502 individuals from the New Jersey Language and Autism Genetics Study (NJLAGS) cohort. Participants were divided into four diagnostic groups: unaffected, ASD-only, LI-only, and ASD + LI. For each language measure, RDI was defined as the product of the total number of test items and the sum of the weight (based on item difficulty) of test items missed. Group differences in RDI were assessed, and the relationship between RDI and ASD diagnosis among individuals with LI was investigated for each language assessment. RESULTS: Although standard scores were unable to distinguish the LI-only and ASD/ASD + LI groups, the ASD/ASD + LI groups had higher RDI scores compared to LI-only group across all measures of expressive, pragmatic, and metalinguistic language. RDI was positively correlated with quantitative ASD traits across all subgroups and was an effective predictor of ASD diagnosis among individuals with LI. CONCLUSIONS: The RDI is an effective quantitative metric of developmental deviance/difference that correlates with ASD traits, supporting previous associations between ASD and non-sequential skill acquisition. The RDI can be adapted to other clinical measures to investigate the degree of difference that is not captured by standard performance summary scores. En ligne : https://dx.doi.org/10.1186/s11689-019-9283-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Early negative affect in males and females with fragile X syndrome: implications for anxiety and autism / Carla A. WALL in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 22 p. Titre : Early negative affect in males and females with fragile X syndrome: implications for anxiety and autism Type de document : Texte imprimé et/ou numérique Auteurs : Carla A. WALL, Auteur ; A. L. HOGAN, Auteur ; Elizabeth A. WILL, Auteur ; S. MCQUILLIN, Auteur ; B. L. KELLEHER, Auteur ; J. E. ROBERTS, Auteur Article en page(s) : 22 p. Langues : Anglais (eng) Mots-clés : Anxiety  Autism spectrum disorder  Fragile X syndrome  Negative affect  Sex differences Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is a genetic disorder that is highly comorbid with anxiety and autism spectrum disorder (ASD). Elevated negative affect in young children has been associated with increased risk for both anxiety and ASD; however, these relations remain poorly understood in FXS. METHODS: The present prospective longitudinal study examined the trajectory of negative affect from infancy through preschool in males and females with FXS and typical development and its relation to anxiety and ASD. RESULTS: Results indicate a complex association reflecting group, developmental, and sex effects. Specifically, the group with FXS displayed a trajectory of increasing negative affect across age that was distinct from the typical controls. This atypical trajectory of negative affect in FXS was driven by sex effects in that males showed lower negative affect during infancy followed by steep increases across the toddler and preschool years whereas the females displayed a flatter trajectory. Finally, elevated negative affect predicted anxiety symptoms in males, but not females, with no relationship to ASD in males or females with FXS. CONCLUSIONS: The current work addresses the importance of studying the development of psychopathology in a specific neurogenetic population. Temperamental negative affect was shown to be an important early marker for anxiety in young children with FXS, with subtle differences observed between males and females. En ligne : https://dx.doi.org/10.1186/s11689-019-9284-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Early negative affect in males and females with fragile X syndrome: implications for anxiety and autism [Texte imprimé et/ou numérique] / Carla A. WALL, Auteur ; A. L. HOGAN, Auteur ; Elizabeth A. WILL, Auteur ; S. MCQUILLIN, Auteur ; B. L. KELLEHER, Auteur ; J. E. ROBERTS, Auteur . - 22 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 22 p. Mots-clés : Anxiety  Autism spectrum disorder  Fragile X syndrome  Negative affect  Sex differences Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is a genetic disorder that is highly comorbid with anxiety and autism spectrum disorder (ASD). Elevated negative affect in young children has been associated with increased risk for both anxiety and ASD; however, these relations remain poorly understood in FXS. METHODS: The present prospective longitudinal study examined the trajectory of negative affect from infancy through preschool in males and females with FXS and typical development and its relation to anxiety and ASD. RESULTS: Results indicate a complex association reflecting group, developmental, and sex effects. Specifically, the group with FXS displayed a trajectory of increasing negative affect across age that was distinct from the typical controls. This atypical trajectory of negative affect in FXS was driven by sex effects in that males showed lower negative affect during infancy followed by steep increases across the toddler and preschool years whereas the females displayed a flatter trajectory. Finally, elevated negative affect predicted anxiety symptoms in males, but not females, with no relationship to ASD in males or females with FXS. CONCLUSIONS: The current work addresses the importance of studying the development of psychopathology in a specific neurogenetic population. Temperamental negative affect was shown to be an important early marker for anxiety in young children with FXS, with subtle differences observed between males and females. En ligne : https://dx.doi.org/10.1186/s11689-019-9284-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Behavioural and psychological characteristics in Pitt-Hopkins syndrome: a comparison with Angelman and Cornelia de Lange syndromes / A. WATKINS in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 24 p. Titre : Behavioural and psychological characteristics in Pitt-Hopkins syndrome: a comparison with Angelman and Cornelia de Lange syndromes Type de document : Texte imprimé et/ou numérique Auteurs : A. WATKINS, Auteur ; S. BISSELL, Auteur ; J. MOSS, Auteur ; C. OLIVER, Auteur ; J. CLAYTON-SMITH, Auteur ; L. HAYE, Auteur ; M. HEALD, Auteur ; A. WELHAM, Auteur Article en page(s) : 24 p. Langues : Anglais (eng) Mots-clés : Angelman syndrome  Autism spectrum disorder  Behavioural phenotype  Cornelia de Lange syndrome  Pitt-Hopkins syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Pitt-Hopkins syndrome (PTHS) is a genetic neurodevelopmental disorder associated with intellectual disability. Although the genetic mechanisms underlying the disorder have been identified, description of its behavioural phenotype is in its infancy. In this study, reported behavioural and psychological characteristics of individuals with PTHS were investigated in comparison with the reported behaviour of age-matched individuals with Angelman syndrome (AS) and Cornelia de Lange syndrome (CdLS). METHODS: Questionnaire data were collected from parents/caregivers of individuals with PTHS (n = 24), assessing behaviours associated with autism spectrum disorder (ASD), sociability, mood, repetitive behaviour, sensory processing, challenging behaviours and overactivity and impulsivity. For most measures, data were compared to data for people with AS (n = 24) and CdLS (n = 24) individually matched by adaptive ability, age and sex. RESULTS: Individuals with PTHS evidenced significantly higher levels of difficulties with social communication and reciprocal social interaction than individuals with AS, with 21 of 22 participants with PTHS meeting criteria indicative of ASD on a screening instrument. Individuals with PTHS were reported to be less sociable with familiar and unfamiliar people than individuals with AS, but more sociable with unfamiliar people than individuals with CdLS. Data also suggested areas of atypicality in sensory experiences. Challenging behaviours were reported frequently in PTHS, with self-injury (70.8%) occurring at significantly higher rates than in AS (41.7%) and aggression (54.2%) occurring at significantly higher rates than in CdLS (25%). Individuals with PTHS also evidenced lower reported mood than individuals with AS. CONCLUSIONS: Behaviours which may be characteristic of PTHS include those associated with ASD, including deficits in social communication and reciprocal social interaction. High rates of aggression and self-injurious behaviour compared to other genetic syndrome groups are of potential clinical significance and warrant further investigation. An atypical sensory profile may also be evident in PTHS. The specific aetiology of and relationships between different behavioural and psychological atypicalities in PTHS, and effective clinical management of these, present potential topics for future research. En ligne : https://dx.doi.org/10.1186/s11689-019-9282-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Behavioural and psychological characteristics in Pitt-Hopkins syndrome: a comparison with Angelman and Cornelia de Lange syndromes [Texte imprimé et/ou numérique] / A. WATKINS, Auteur ; S. BISSELL, Auteur ; J. MOSS, Auteur ; C. OLIVER, Auteur ; J. CLAYTON-SMITH, Auteur ; L. HAYE, Auteur ; M. HEALD, Auteur ; A. WELHAM, Auteur . - 24 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 24 p. Mots-clés : Angelman syndrome  Autism spectrum disorder  Behavioural phenotype  Cornelia de Lange syndrome  Pitt-Hopkins syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Pitt-Hopkins syndrome (PTHS) is a genetic neurodevelopmental disorder associated with intellectual disability. Although the genetic mechanisms underlying the disorder have been identified, description of its behavioural phenotype is in its infancy. In this study, reported behavioural and psychological characteristics of individuals with PTHS were investigated in comparison with the reported behaviour of age-matched individuals with Angelman syndrome (AS) and Cornelia de Lange syndrome (CdLS). METHODS: Questionnaire data were collected from parents/caregivers of individuals with PTHS (n = 24), assessing behaviours associated with autism spectrum disorder (ASD), sociability, mood, repetitive behaviour, sensory processing, challenging behaviours and overactivity and impulsivity. For most measures, data were compared to data for people with AS (n = 24) and CdLS (n = 24) individually matched by adaptive ability, age and sex. RESULTS: Individuals with PTHS evidenced significantly higher levels of difficulties with social communication and reciprocal social interaction than individuals with AS, with 21 of 22 participants with PTHS meeting criteria indicative of ASD on a screening instrument. Individuals with PTHS were reported to be less sociable with familiar and unfamiliar people than individuals with AS, but more sociable with unfamiliar people than individuals with CdLS. Data also suggested areas of atypicality in sensory experiences. Challenging behaviours were reported frequently in PTHS, with self-injury (70.8%) occurring at significantly higher rates than in AS (41.7%) and aggression (54.2%) occurring at significantly higher rates than in CdLS (25%). Individuals with PTHS also evidenced lower reported mood than individuals with AS. CONCLUSIONS: Behaviours which may be characteristic of PTHS include those associated with ASD, including deficits in social communication and reciprocal social interaction. High rates of aggression and self-injurious behaviour compared to other genetic syndrome groups are of potential clinical significance and warrant further investigation. An atypical sensory profile may also be evident in PTHS. The specific aetiology of and relationships between different behavioural and psychological atypicalities in PTHS, and effective clinical management of these, present potential topics for future research. En ligne : https://dx.doi.org/10.1186/s11689-019-9282-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Developmental divergence: motor trajectories in children with fragile X syndrome with and without co-occurring autism / Elizabeth A. WILL in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 23 p. Titre : Developmental divergence: motor trajectories in children with fragile X syndrome with and without co-occurring autism Type de document : Texte imprimé et/ou numérique Auteurs : Elizabeth A. WILL, Auteur ; Somer L. BISHOP, Auteur ; J. E. ROBERTS, Auteur Article en page(s) : 23 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Developmental trajectories  Fragile X syndrome  Motor development Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is highly prevalent in fragile X syndrome (FXS), affecting 50-70% of males. Motor impairments are a shared feature across autism and FXS that may help to better characterize autism in FXS. As motor skills provide a critical foundation for various language, cognitive, and social outcomes, they may serve an important mechanistic role for autism in FXS. As such, this study aimed to identify differences in motor trajectories across direct assessment and parent-report measures of fine and gross motor development between FXS with and without autism, and typical development, while controlling for cognitive functioning. METHODS: This prospective longitudinal study included 42 children with FXS, 24 of whom also had ASD (FXS + ASD), as well as 40 typically developing children. The Mullen Scales of Early Learning provided a direct measure of fine and gross motor skills, and the Vineland Adaptive Behavior Scales provided a measure of parent-reported fine and gross motor skills. Random slopes and random intercepts multilevel models were tested to determine divergence in developmental motor trajectories between groups when controlling for cognitive level. RESULTS: Model results indicated the children with FXS + ASD diverged from TD children by 9-months on all measures of gross and fine motor skills, even when controlling for cognitive level. Results also indicated an early divergence in motor trajectories of fine and gross motor skills between the FXS + ASD and FXS groups when controlling for cognitive level. This divergence was statistically significant by 18 months, with the FXS + ASD showing decelerated growth in motor skills across direct observation and parent-report measures. CONCLUSIONS: This study is the first to examine longitudinal trends in motor development in children with FXS with and without comorbid ASD using both direct assessment and parent-report measures of fine and gross motor. Furthermore, it is among the first to account for nonverbal cognitive delays, a step towards elucidating the isolated role of motor impairments in FXS with and without ASD. Findings underscore the role of motor impairments as a possible signal representing greater underlying genetic liability, or as a potential catalyst or consequence, of co-occurring autism in FXS. En ligne : https://dx.doi.org/10.1186/s11689-019-9281-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Developmental divergence: motor trajectories in children with fragile X syndrome with and without co-occurring autism [Texte imprimé et/ou numérique] / Elizabeth A. WILL, Auteur ; Somer L. BISHOP, Auteur ; J. E. ROBERTS, Auteur . - 23 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 23 p. Mots-clés : Autism spectrum disorder  Developmental trajectories  Fragile X syndrome  Motor development Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is highly prevalent in fragile X syndrome (FXS), affecting 50-70% of males. Motor impairments are a shared feature across autism and FXS that may help to better characterize autism in FXS. As motor skills provide a critical foundation for various language, cognitive, and social outcomes, they may serve an important mechanistic role for autism in FXS. As such, this study aimed to identify differences in motor trajectories across direct assessment and parent-report measures of fine and gross motor development between FXS with and without autism, and typical development, while controlling for cognitive functioning. METHODS: This prospective longitudinal study included 42 children with FXS, 24 of whom also had ASD (FXS + ASD), as well as 40 typically developing children. The Mullen Scales of Early Learning provided a direct measure of fine and gross motor skills, and the Vineland Adaptive Behavior Scales provided a measure of parent-reported fine and gross motor skills. Random slopes and random intercepts multilevel models were tested to determine divergence in developmental motor trajectories between groups when controlling for cognitive level. RESULTS: Model results indicated the children with FXS + ASD diverged from TD children by 9-months on all measures of gross and fine motor skills, even when controlling for cognitive level. Results also indicated an early divergence in motor trajectories of fine and gross motor skills between the FXS + ASD and FXS groups when controlling for cognitive level. This divergence was statistically significant by 18 months, with the FXS + ASD showing decelerated growth in motor skills across direct observation and parent-report measures. CONCLUSIONS: This study is the first to examine longitudinal trends in motor development in children with FXS with and without comorbid ASD using both direct assessment and parent-report measures of fine and gross motor. Furthermore, it is among the first to account for nonverbal cognitive delays, a step towards elucidating the isolated role of motor impairments in FXS with and without ASD. Findings underscore the role of motor impairments as a possible signal representing greater underlying genetic liability, or as a potential catalyst or consequence, of co-occurring autism in FXS. En ligne : https://dx.doi.org/10.1186/s11689-019-9281-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Vocabulary comprehension in adults with fragile X syndrome (FXS) / A. HOFFMANN in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 25 p. Titre : Vocabulary comprehension in adults with fragile X syndrome (FXS) Type de document : Texte imprimé et/ou numérique Auteurs : A. HOFFMANN, Auteur ; S. E. KRAUSE, Auteur ; J. WUU, Auteur ; S. LEURGANS, Auteur ; S. J. GUTER, Auteur ; S. S. BLOCK, Auteur ; J. SALT, Auteur ; E. COOK, Auteur ; D. M. MAINO, Auteur ; Elizabeth BERRY-KRAVIS, Auteur Article en page(s) : 25 p. Langues : Anglais (eng) Mots-clés : Adults  Cognition  Comprehension  Fragile X syndrome  Language  Vocabulary Index. décimale : PER Périodiques Résumé : BACKGROUND: Receptive and expressive vocabulary in adult and adolescent males with fragile X syndrome (FXS) have been shown as significantly lower than their chronological age; however, receptive vocabulary has been considered a strength relative to mental age. This has not been formally examined, however, and data are needed to compare receptive vocabulary with other language skills and with mental age in individuals with FXS. This is especially important as vocabulary measures are sometimes used as a proxy to estimate language ability. METHODS: This preliminary study examined receptive vocabulary, global language, and cognitive skills in 42 adults (33 males and 9 females) with FXS as a portion of the baseline evaluation prior to randomization in a clinical trial of ampakine CX516. The battery of standardized tests addressed receptive vocabulary with the Peabody Picture Vocabulary Test, Third Edition (PPVT-III), receptive and expressive language (termed henceforth as global language) via the Preschool Language Scale, Fourth Edition or the Clinical Evaluation of Language Fundamentals, Third Edition, and non-verbal cognition via the Stanford-Binet Intelligence Scales, Fourth Edition (SB-IV). RESULTS: Results showed (1) significantly higher receptive vocabulary than global language, (2) significantly better receptive vocabulary than non-verbal cognition, (3) equivalent non-verbal cognition and global language, and (4) severity of autism symptomatology was not correlated to receptive vocabulary or global language once non-verbal cognition was removed as factor. The scores from the PPVT-III did not represent the global language skills in our sample of adults with FXS. CONCLUSIONS: Findings from this investigation strongly suggest that the PPVT-III should not be used as a screening tool for language levels or cognitive function in clinical studies since the scores from the PPVT-III were not representative of global language or non-verbal cognitive skills in adults with intellectual disabilities. This finding is critical in order to understand how to evaluate, as well as to treat, language in individuals with FXS. Development of efficient and appropriate tools to measure language, cognition, and behavior in individuals with FXS is essential. En ligne : https://dx.doi.org/10.1186/s11689-019-9285-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Vocabulary comprehension in adults with fragile X syndrome (FXS) [Texte imprimé et/ou numérique] / A. HOFFMANN, Auteur ; S. E. KRAUSE, Auteur ; J. WUU, Auteur ; S. LEURGANS, Auteur ; S. J. GUTER, Auteur ; S. S. BLOCK, Auteur ; J. SALT, Auteur ; E. COOK, Auteur ; D. M. MAINO, Auteur ; Elizabeth BERRY-KRAVIS, Auteur . - 25 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 25 p. Mots-clés : Adults  Cognition  Comprehension  Fragile X syndrome  Language  Vocabulary Index. décimale : PER Périodiques Résumé : BACKGROUND: Receptive and expressive vocabulary in adult and adolescent males with fragile X syndrome (FXS) have been shown as significantly lower than their chronological age; however, receptive vocabulary has been considered a strength relative to mental age. This has not been formally examined, however, and data are needed to compare receptive vocabulary with other language skills and with mental age in individuals with FXS. This is especially important as vocabulary measures are sometimes used as a proxy to estimate language ability. METHODS: This preliminary study examined receptive vocabulary, global language, and cognitive skills in 42 adults (33 males and 9 females) with FXS as a portion of the baseline evaluation prior to randomization in a clinical trial of ampakine CX516. The battery of standardized tests addressed receptive vocabulary with the Peabody Picture Vocabulary Test, Third Edition (PPVT-III), receptive and expressive language (termed henceforth as global language) via the Preschool Language Scale, Fourth Edition or the Clinical Evaluation of Language Fundamentals, Third Edition, and non-verbal cognition via the Stanford-Binet Intelligence Scales, Fourth Edition (SB-IV). RESULTS: Results showed (1) significantly higher receptive vocabulary than global language, (2) significantly better receptive vocabulary than non-verbal cognition, (3) equivalent non-verbal cognition and global language, and (4) severity of autism symptomatology was not correlated to receptive vocabulary or global language once non-verbal cognition was removed as factor. The scores from the PPVT-III did not represent the global language skills in our sample of adults with FXS. CONCLUSIONS: Findings from this investigation strongly suggest that the PPVT-III should not be used as a screening tool for language levels or cognitive function in clinical studies since the scores from the PPVT-III were not representative of global language or non-verbal cognitive skills in adults with intellectual disabilities. This finding is critical in order to understand how to evaluate, as well as to treat, language in individuals with FXS. Development of efficient and appropriate tools to measure language, cognition, and behavior in individuals with FXS is essential. En ligne : https://dx.doi.org/10.1186/s11689-019-9285-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Quantitative gait assessment in children with 16p11.2 syndrome / S. GOLDMAN in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 26 p. Titre : Quantitative gait assessment in children with 16p11.2 syndrome Type de document : Texte imprimé et/ou numérique Auteurs : S. GOLDMAN, Auteur ; A. K. MCCULLOUGH, Auteur ; S. D. YOUNG, Auteur ; C. MUELLER, Auteur ; A. STAHL, Auteur ; A. ZOELLER, Auteur ; L. D. ABBRUZZESE, Auteur ; A. K. RAO, Auteur ; J. MONTES, Auteur Article en page(s) : 26 p. Langues : Anglais (eng) Mots-clés : 16p11.2  Autism spectrum disorder  Children  Gait  Motor function  Neurodevelopment disorder Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurodevelopmental disorders such as 16p11.2 syndrome are frequently associated with motor impairments including locomotion. The lack of precise measures of gait, combined with the challenges inherent in studying children with neurodevelopmental disorders, hinders quantitative motor assessments. Gait and balance are quantifiable measures that may help to refine the motor phenotype in 16p11.2. The characterization of motor profile is useful to study the trajectories of locomotion performance of children with genetic variants and may provide insights into neural pathway dysfunction based on genotype/phenotype model. METHODS: Thirty-six children (21 probands with 16p11.2 deletion and duplication mutation and 15 unaffected siblings), with a mean age of 8.5 years (range 3.2-15.4) and 55% male, were enrolled. Of the probands, 23% (n = 6) had a confirmed diagnosis of autism spectrum disorder (ASD) and were all male. Gait assessments included 6-min walk test (6MWT), 10-m walk/run test (10MWR), timed-up-and-go test (TUG), and spatio-temporal measurements of preferred- and fast-paced walking. The Pediatric Evaluation of Disability Inventory-Computer Adaptive Tests (PEDI-CAT), a caregiver-reported functional assessment, was administered. Measures of balance were calculated using percent time in double support and base of support. Analyses of the six children with ASD were described separately. RESULTS: Thirty-six participants completed the protocol. Compared with sibling controls, probands had significantly lower scores on the 6MWT (p = 0.04), 10MWR (p = 0.01), and TUG (p = 0.005). Group differences were also identified in base of support (p = 0.003). Probands had significantly lower PEDI-CAT scores in all domains including the mobility scale (p < 0.001). Using age-matched subsamples, the ASD and non-ASD genetic variant groups had larger base of support compared to the controls. In the fast-paced condition, all participants increased their velocity, and there was a corresponding decrease in percent time in double support compared to the preferred-pace condition in all participants. Only the ASD group presented with upper limb arm/hand stereotypies. CONCLUSIONS: Children with 16p11.2, with and without ASD, present with balance impairment during locomotion activities. Probands performed worse on functional assessments, and quantitative measures revealed differences in base of support. These results highlight the importance of using precise measures to differentiate motor dysfunction in children with neurodevelopmental disorders. En ligne : https://dx.doi.org/10.1186/s11689-019-9286-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Quantitative gait assessment in children with 16p11.2 syndrome [Texte imprimé et/ou numérique] / S. GOLDMAN, Auteur ; A. K. MCCULLOUGH, Auteur ; S. D. YOUNG, Auteur ; C. MUELLER, Auteur ; A. STAHL, Auteur ; A. ZOELLER, Auteur ; L. D. ABBRUZZESE, Auteur ; A. K. RAO, Auteur ; J. MONTES, Auteur . - 26 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 26 p. Mots-clés : 16p11.2  Autism spectrum disorder  Children  Gait  Motor function  Neurodevelopment disorder Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurodevelopmental disorders such as 16p11.2 syndrome are frequently associated with motor impairments including locomotion. The lack of precise measures of gait, combined with the challenges inherent in studying children with neurodevelopmental disorders, hinders quantitative motor assessments. Gait and balance are quantifiable measures that may help to refine the motor phenotype in 16p11.2. The characterization of motor profile is useful to study the trajectories of locomotion performance of children with genetic variants and may provide insights into neural pathway dysfunction based on genotype/phenotype model. METHODS: Thirty-six children (21 probands with 16p11.2 deletion and duplication mutation and 15 unaffected siblings), with a mean age of 8.5 years (range 3.2-15.4) and 55% male, were enrolled. Of the probands, 23% (n = 6) had a confirmed diagnosis of autism spectrum disorder (ASD) and were all male. Gait assessments included 6-min walk test (6MWT), 10-m walk/run test (10MWR), timed-up-and-go test (TUG), and spatio-temporal measurements of preferred- and fast-paced walking. The Pediatric Evaluation of Disability Inventory-Computer Adaptive Tests (PEDI-CAT), a caregiver-reported functional assessment, was administered. Measures of balance were calculated using percent time in double support and base of support. Analyses of the six children with ASD were described separately. RESULTS: Thirty-six participants completed the protocol. Compared with sibling controls, probands had significantly lower scores on the 6MWT (p = 0.04), 10MWR (p = 0.01), and TUG (p = 0.005). Group differences were also identified in base of support (p = 0.003). Probands had significantly lower PEDI-CAT scores in all domains including the mobility scale (p < 0.001). Using age-matched subsamples, the ASD and non-ASD genetic variant groups had larger base of support compared to the controls. In the fast-paced condition, all participants increased their velocity, and there was a corresponding decrease in percent time in double support compared to the preferred-pace condition in all participants. Only the ASD group presented with upper limb arm/hand stereotypies. CONCLUSIONS: Children with 16p11.2, with and without ASD, present with balance impairment during locomotion activities. Probands performed worse on functional assessments, and quantitative measures revealed differences in base of support. These results highlight the importance of using precise measures to differentiate motor dysfunction in children with neurodevelopmental disorders. En ligne : https://dx.doi.org/10.1186/s11689-019-9286-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409