Characterization of autism spectrum disorder and neurodevelopmental profiles in youth with XYY syndrome / L. JOSEPH in Journal of Neurodevelopmental Disorders, 10-1 (December 2018)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 10-1 (December 2018) . - 30 p. Titre : Characterization of autism spectrum disorder and neurodevelopmental profiles in youth with XYY syndrome Type de document : Texte imprimé et/ou numérique Auteurs : L. JOSEPH, Auteur ; C. FARMER, Auteur ; C. CHLEBOWSKI, Auteur ; L. HENRY, Auteur ; A. FISH, Auteur ; C. MANKIW, Auteur ; A. XENOPHONTOS, Auteur ; L. CLASEN, Auteur ; B. SAULS, Auteur ; J. SEIDLITZ, Auteur ; Jonathan D. BLUMENTHAL, Auteur ; E. TORRES, Auteur ; A. THURM, Auteur ; A. RAZNAHAN, Auteur Année de publication : 2018 Article en page(s) : 30 p. Langues : Anglais (eng) Mots-clés : Adaptive behavior  Autism spectrum disorder symptoms  Cognitive functioning  Learning disabilities  Sex chromosome aneuploidies Index. décimale : PER Périodiques Résumé : BACKGROUND: XYY syndrome is a sex chromosome aneuploidy that occurs in ~ 1/850 male births and is associated with increased risk for neurodevelopmental difficulties. However, the profile of neurodevelopmental impairments, including symptoms of autism spectrum disorder (ASD) in XYY remains poorly understood. This gap in knowledge has persisted in part due to lack of access to patient cohorts with dense and homogeneous phenotypic data. METHODS: We evaluated a single-center cohort of 64 individuals with XYY aged 5-25 years, using a standardized battery of cognitive and behavioral assessments spanning developmental milestones, IQ, adaptive behavior, academic achievement, behavioral problems, and gold-standard diagnostic instruments for ASD. Our goals were to (i) detail the neurodevelopmental profile of XYY with a focus on ASD diagnostic rates and symptom profiles, (ii) screen phenotypes for potential ascertainment bias effects by contrasting pre- vs. postnatally diagnosed XYY subgroups, and (iii) define major modules of phenotypic variation using graph-theoretical analysis. RESULTS: Although there was marked inter-individual variability, the average profile was characterized by some degree of developmental delay, and decreased IQ and adaptive behavior. Impairments were most pronounced for language and socio-communicative functioning. The rate of ASD was 14%, and these individuals exhibited autism symptom profiles resembling those observed in ASD without XYY. Most neurodevelopmental dimensions showed milder impairment among pre- vs. postnatally diagnosed individuals, with clinically meaningful differences in verbal IQ. Feature network analysis revealed three reliably separable modules comprising (i) cognition and academic achievement, (ii) broad domain psychopathology and adaptive behavior, and (iii) ASD-related features. CONCLUSIONS: By adding granularity to our understanding of neurodevelopmental difficulties in XYY, these findings assist targeted clinical assessment of newly identified cases, motivate greater provision of specialized multidisciplinary support, and inform future efforts to integrate behavioral phenotypes in XYY with neurobiology. TRIAL REGISTRATIONS: ClinicalTrials.gov NCT00001246 , "89-M-0006: Brain Imaging of Childhood Onset Psychiatric Disorders, Endocrine Disorders and Healthy Controls." En ligne : http://dx.doi.org/10.1186/s11689-018-9248-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386 [article] Characterization of autism spectrum disorder and neurodevelopmental profiles in youth with XYY syndrome [Texte imprimé et/ou numérique] / L. JOSEPH, Auteur ; C. FARMER, Auteur ; C. CHLEBOWSKI, Auteur ; L. HENRY, Auteur ; A. FISH, Auteur ; C. MANKIW, Auteur ; A. XENOPHONTOS, Auteur ; L. CLASEN, Auteur ; B. SAULS, Auteur ; J. SEIDLITZ, Auteur ; Jonathan D. BLUMENTHAL, Auteur ; E. TORRES, Auteur ; A. THURM, Auteur ; A. RAZNAHAN, Auteur . - 2018 . - 30 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 10-1 (December 2018) . - 30 p. Mots-clés : Adaptive behavior  Autism spectrum disorder symptoms  Cognitive functioning  Learning disabilities  Sex chromosome aneuploidies Index. décimale : PER Périodiques Résumé : BACKGROUND: XYY syndrome is a sex chromosome aneuploidy that occurs in ~ 1/850 male births and is associated with increased risk for neurodevelopmental difficulties. However, the profile of neurodevelopmental impairments, including symptoms of autism spectrum disorder (ASD) in XYY remains poorly understood. This gap in knowledge has persisted in part due to lack of access to patient cohorts with dense and homogeneous phenotypic data. METHODS: We evaluated a single-center cohort of 64 individuals with XYY aged 5-25 years, using a standardized battery of cognitive and behavioral assessments spanning developmental milestones, IQ, adaptive behavior, academic achievement, behavioral problems, and gold-standard diagnostic instruments for ASD. Our goals were to (i) detail the neurodevelopmental profile of XYY with a focus on ASD diagnostic rates and symptom profiles, (ii) screen phenotypes for potential ascertainment bias effects by contrasting pre- vs. postnatally diagnosed XYY subgroups, and (iii) define major modules of phenotypic variation using graph-theoretical analysis. RESULTS: Although there was marked inter-individual variability, the average profile was characterized by some degree of developmental delay, and decreased IQ and adaptive behavior. Impairments were most pronounced for language and socio-communicative functioning. The rate of ASD was 14%, and these individuals exhibited autism symptom profiles resembling those observed in ASD without XYY. Most neurodevelopmental dimensions showed milder impairment among pre- vs. postnatally diagnosed individuals, with clinically meaningful differences in verbal IQ. Feature network analysis revealed three reliably separable modules comprising (i) cognition and academic achievement, (ii) broad domain psychopathology and adaptive behavior, and (iii) ASD-related features. CONCLUSIONS: By adding granularity to our understanding of neurodevelopmental difficulties in XYY, these findings assist targeted clinical assessment of newly identified cases, motivate greater provision of specialized multidisciplinary support, and inform future efforts to integrate behavioral phenotypes in XYY with neurobiology. TRIAL REGISTRATIONS: ClinicalTrials.gov NCT00001246 , "89-M-0006: Brain Imaging of Childhood Onset Psychiatric Disorders, Endocrine Disorders and Healthy Controls." En ligne : http://dx.doi.org/10.1186/s11689-018-9248-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386

Development, behavior, and biomarker characterization of Smith-Lemli-Opitz syndrome: an update / A. THURM in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.12 Titre : Development, behavior, and biomarker characterization of Smith-Lemli-Opitz syndrome: an update Type de document : Texte imprimé et/ou numérique Auteurs : A. THURM, Auteur ; E. TIERNEY, Auteur ; C. FARMER, Auteur ; P. ALBERT, Auteur ; L. JOSEPH, Auteur ; Susan E. SWEDO, Auteur ; S. BIANCONI, Auteur ; I. BUKELIS, Auteur ; C. WHEELER, Auteur ; G. SARPHARE, Auteur ; D. LANHAM, Auteur ; C. A. WASSIF, Auteur ; F. D. PORTER, Auteur Article en page(s) : p.12 Langues : Anglais (eng) Mots-clés : Autism  Developmental delay  Smith-Lemli-Opitz  Sterols Index. décimale : PER Périodiques Résumé : BACKGROUND: Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive inborn error of cholesterol metabolism syndrome with neurocognitive manifestations. SLOS is the result of mutations in the gene encoding the 7-dehydrocholesterol reductase, which results in the elevation of the cholesterol precursor 7-dehydrocholesterol (7-DHC). Previous reports indicate that intellectual disability, behavioral disturbances, and autism symptoms are frequently part of the SLOS behavioral phenotype. In the current study, we characterize the developmental history and current behavior of 33 individuals with SLOS aged 4 to 23 years and report on biomarkers 7-DHC and 8-DHC in relation to cognition and behavior. METHODS: This was an observational case series, wherein participants with SLOS underwent extensive behavioral evaluation of cognitive function, adaptive function, autism symptoms, and problem behaviors, in addition to parent report of developmental milestones. Serum and CSF were contemporaneously obtained from the majority of participants. RESULTS: Developmental milestones such as walking, talking, and toileting were uniformly delayed. Overall levels of cognitive and adaptive functioning were low; no participant received adaptive behavior scores in the average range, and the mean level of cognitive functioning in the full sample was in the moderate range of impairment. Aggressive behavior was present in nearly half of participants. Although the majority of participants had elevated scores on the gold standard autism diagnostic instruments, only about half of participants received a clinical diagnosis of autism spectrum disorder. Finally, while CSF cholesterol was not found to correlate with cognitive or adaptive functioning, both serum and CSF 7-DHC and 8-DHC (and their ratios with cholesterol) were moderately and negatively correlated with functioning in this group. CONCLUSIONS: A history of developmental delay, followed by intellectual disability, is common in individuals with SLOS. Although autism spectrum disorder appears to be a frequent diagnosis in this population, it is apparent that the low level of functioning observed in SLOS may artificially inflate scores on standard autism assessments. Our findings further support that cholesterol precursors 7-DHC and 8-DHC are important biomarkers of the level of functioning in SLOS, especially regarding cognitive abilities, and thus may be to explore as mediators within the context of treatment trials. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00001721, NCT00064792. En ligne : http://dx.doi.org/10.1186/s11689-016-9145-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] Development, behavior, and biomarker characterization of Smith-Lemli-Opitz syndrome: an update [Texte imprimé et/ou numérique] / A. THURM, Auteur ; E. TIERNEY, Auteur ; C. FARMER, Auteur ; P. ALBERT, Auteur ; L. JOSEPH, Auteur ; Susan E. SWEDO, Auteur ; S. BIANCONI, Auteur ; I. BUKELIS, Auteur ; C. WHEELER, Auteur ; G. SARPHARE, Auteur ; D. LANHAM, Auteur ; C. A. WASSIF, Auteur ; F. D. PORTER, Auteur . - p.12. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.12 Mots-clés : Autism  Developmental delay  Smith-Lemli-Opitz  Sterols Index. décimale : PER Périodiques Résumé : BACKGROUND: Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive inborn error of cholesterol metabolism syndrome with neurocognitive manifestations. SLOS is the result of mutations in the gene encoding the 7-dehydrocholesterol reductase, which results in the elevation of the cholesterol precursor 7-dehydrocholesterol (7-DHC). Previous reports indicate that intellectual disability, behavioral disturbances, and autism symptoms are frequently part of the SLOS behavioral phenotype. In the current study, we characterize the developmental history and current behavior of 33 individuals with SLOS aged 4 to 23 years and report on biomarkers 7-DHC and 8-DHC in relation to cognition and behavior. METHODS: This was an observational case series, wherein participants with SLOS underwent extensive behavioral evaluation of cognitive function, adaptive function, autism symptoms, and problem behaviors, in addition to parent report of developmental milestones. Serum and CSF were contemporaneously obtained from the majority of participants. RESULTS: Developmental milestones such as walking, talking, and toileting were uniformly delayed. Overall levels of cognitive and adaptive functioning were low; no participant received adaptive behavior scores in the average range, and the mean level of cognitive functioning in the full sample was in the moderate range of impairment. Aggressive behavior was present in nearly half of participants. Although the majority of participants had elevated scores on the gold standard autism diagnostic instruments, only about half of participants received a clinical diagnosis of autism spectrum disorder. Finally, while CSF cholesterol was not found to correlate with cognitive or adaptive functioning, both serum and CSF 7-DHC and 8-DHC (and their ratios with cholesterol) were moderately and negatively correlated with functioning in this group. CONCLUSIONS: A history of developmental delay, followed by intellectual disability, is common in individuals with SLOS. Although autism spectrum disorder appears to be a frequent diagnosis in this population, it is apparent that the low level of functioning observed in SLOS may artificially inflate scores on standard autism assessments. Our findings further support that cholesterol precursors 7-DHC and 8-DHC are important biomarkers of the level of functioning in SLOS, especially regarding cognitive abilities, and thus may be to explore as mediators within the context of treatment trials. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00001721, NCT00064792. En ligne : http://dx.doi.org/10.1186/s11689-016-9145-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

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