Clinical, genetic, and cognitive correlates of seizure occurrences in Phelan-McDermid syndrome / Tess LEVY in Journal of Neurodevelopmental Disorders, 16 (2024)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 16 (2024) Titre : Clinical, genetic, and cognitive correlates of seizure occurrences in Phelan-McDermid syndrome Type de document : texte imprimé Auteurs : Tess LEVY, Auteur ; Jacob GLUCKMAN, Auteur ; Paige M. SIPER, Auteur ; Danielle HALPERN, Auteur ; Jessica ZWEIFACH, Auteur ; Rajna FILIP-DHIMA, Auteur ; J. Lloyd Jr HOLDER, Auteur ; M. Pilar TRELLES, Auteur ; Kristina JOHNSON, Auteur ; Jonathan A. BERNSTEIN, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Craig M. POWELL, Auteur ; Latha Valluripalli SOORYA, Auteur ; Audrey THURM, Auteur ; Joseph D. BUXBAUM, Auteur ; Mustafa SAHIN, Auteur ; Alexander KOLEVZON, Auteur ; Siddharth SRIVASTAVA, Auteur ; DEVELOPMENTAL SYNAPTOPATHIES CONSORTIUM, Auteur Langues : Anglais (eng) Mots-clés : Humans  Male  Female  Seizures/genetics  Chromosome Deletion  Chromosome Disorders/complications/genetics/physiopathology  Chromosomes, Human, Pair 22/genetics  Child  Child, Preschool  Adolescent  Longitudinal Studies  Young Adult  Adult  Prospective Studies  Infant  Nerve Tissue Proteins/genetics  22q13  Epilepsy  Phelan-McDermid syndrome  Shank3  Seizures Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is a genetic neurodevelopmental disorder caused by SHANK3 haploinsufficiency and is associated with an increased risk for seizures. Previous literature indicates that around one third of individuals with PMS also have epilepsy or seizures, with a wide range of types and ages of onset. Investigating the impact of seizures on intellectual and adaptive functioning for PMS is a primary concern for caregivers and is important to understanding the natural history of this syndrome. METHODS: We report on results from 98 individuals enrolled in a prospective, longitudinal study. We detailed seizure frequency, type, and age of onset, and we analyzed seizure occurrence with best estimate IQ, adaptive functioning, clinical features, and genotype. We conducted multiple linear regression analyses to assess the relationship between the presence of seizures and the Vineland Adaptive Behavior Scale, Second Edition (VABS-II) Adaptive Behavior Composite score and the best estimate full-scale IQ. We also performed Chi-square tests to explore associations between seizure prevalence and genetic groupings. Finally, we performed Chi-square tests and t-tests to explore the relationship between seizures and demographic features, features that manifest in infancy, and medical features. RESULTS: Seizures were present in 41% of the cohort, and age of onset was widely variable. The presence of seizures was associated with significantly lower adaptive and intellectual functioning. Genotype-phenotype analyses were discrepant, with no differences in seizure prevalence across genetic classes, but with more genes included in deletions of participants with 22q13 deletions and seizures compared to those with 22q13 deletions and no seizures. No clinical associations were found between the presence of seizures and sex, history of pre- or neonatal complications, early infancy, or medical features. In this cohort, generalized seizures were associated with developmental regression, which is a top concern for PMS caregivers. CONCLUSIONS: These results begin to eludicate correlates of seizures in individuals with PMS and highlight the importance of early seizure management. Importantly, presence of seizures was associated with adaptive and cognitive functioning. A larger cohort might be able to identify additional associations with medical features. Genetic findings suggest an increased capability to realize genotype-phenotype relationships when deletion size is taken into account. En ligne : https://dx.doi.org/10.1186/s11689-024-09541-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575 [article] Clinical, genetic, and cognitive correlates of seizure occurrences in Phelan-McDermid syndrome [texte imprimé] / Tess LEVY, Auteur ; Jacob GLUCKMAN, Auteur ; Paige M. SIPER, Auteur ; Danielle HALPERN, Auteur ; Jessica ZWEIFACH, Auteur ; Rajna FILIP-DHIMA, Auteur ; J. Lloyd Jr HOLDER, Auteur ; M. Pilar TRELLES, Auteur ; Kristina JOHNSON, Auteur ; Jonathan A. BERNSTEIN, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Craig M. POWELL, Auteur ; Latha Valluripalli SOORYA, Auteur ; Audrey THURM, Auteur ; Joseph D. BUXBAUM, Auteur ; Mustafa SAHIN, Auteur ; Alexander KOLEVZON, Auteur ; Siddharth SRIVASTAVA, Auteur ; DEVELOPMENTAL SYNAPTOPATHIES CONSORTIUM, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 16 (2024) Mots-clés : Humans  Male  Female  Seizures/genetics  Chromosome Deletion  Chromosome Disorders/complications/genetics/physiopathology  Chromosomes, Human, Pair 22/genetics  Child  Child, Preschool  Adolescent  Longitudinal Studies  Young Adult  Adult  Prospective Studies  Infant  Nerve Tissue Proteins/genetics  22q13  Epilepsy  Phelan-McDermid syndrome  Shank3  Seizures Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is a genetic neurodevelopmental disorder caused by SHANK3 haploinsufficiency and is associated with an increased risk for seizures. Previous literature indicates that around one third of individuals with PMS also have epilepsy or seizures, with a wide range of types and ages of onset. Investigating the impact of seizures on intellectual and adaptive functioning for PMS is a primary concern for caregivers and is important to understanding the natural history of this syndrome. METHODS: We report on results from 98 individuals enrolled in a prospective, longitudinal study. We detailed seizure frequency, type, and age of onset, and we analyzed seizure occurrence with best estimate IQ, adaptive functioning, clinical features, and genotype. We conducted multiple linear regression analyses to assess the relationship between the presence of seizures and the Vineland Adaptive Behavior Scale, Second Edition (VABS-II) Adaptive Behavior Composite score and the best estimate full-scale IQ. We also performed Chi-square tests to explore associations between seizure prevalence and genetic groupings. Finally, we performed Chi-square tests and t-tests to explore the relationship between seizures and demographic features, features that manifest in infancy, and medical features. RESULTS: Seizures were present in 41% of the cohort, and age of onset was widely variable. The presence of seizures was associated with significantly lower adaptive and intellectual functioning. Genotype-phenotype analyses were discrepant, with no differences in seizure prevalence across genetic classes, but with more genes included in deletions of participants with 22q13 deletions and seizures compared to those with 22q13 deletions and no seizures. No clinical associations were found between the presence of seizures and sex, history of pre- or neonatal complications, early infancy, or medical features. In this cohort, generalized seizures were associated with developmental regression, which is a top concern for PMS caregivers. CONCLUSIONS: These results begin to eludicate correlates of seizures in individuals with PMS and highlight the importance of early seizure management. Importantly, presence of seizures was associated with adaptive and cognitive functioning. A larger cohort might be able to identify additional associations with medical features. Genetic findings suggest an increased capability to realize genotype-phenotype relationships when deletion size is taken into account. En ligne : https://dx.doi.org/10.1186/s11689-024-09541-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575

Implications of Provider Specialty, Test Type, and Demographic Factors on Genetic Testing Outcomes for Patients with Autism Spectrum Disorder / Caitlin N. HARRINGTON in Journal of Autism and Developmental Disorders, 55-9 (September 2025)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 55-9 (September 2025) . - p.3231-3244 Titre : Implications of Provider Specialty, Test Type, and Demographic Factors on Genetic Testing Outcomes for Patients with Autism Spectrum Disorder Type de document : texte imprimé Auteurs : Caitlin N. HARRINGTON, Auteur ; Ana MORALES, Auteur ; Jonathan A. BERNSTEIN, Auteur ; Laurel CALDERWOOD, Auteur Article en page(s) : p.3231-3244 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : A minority of patients with autism spectrum disorder (ASD) are offered genetic testing by their providers or referred for genetics evaluation despite published guidelines and consensus statements supporting genetics-informed care for this population. This study aimed to investigate the ordering habits of providers of different specialties and to additionally assess the diagnostic utility of genetic testing by test type, patient sex, and race and ethnicity. We retrospectively analyzed data associated with orders for the indication of ASD from a large clinical laboratory over 6 years (2017-2022). Geneticists and neurologists were more likely than other specialists to order exome sequencing and neurodevelopmental (NDD) panel testing while other providers were more likely to order chromosomal microarray (CMA) and Fragile X testing. Exome had the highest diagnostic yield (24.5%), followed by NDD panel (6.4%), CMA (6.2%), and Fragile X testing (0.4%). Females were 1.4x (95% CI: 1.2-1.7) more likely than males to receive a genetic diagnosis. However, for Fragile X, males had a higher diagnostic yield than females (0.4% vs 0.2%). Our findings highlight the need to enable non-genetics providers to order comprehensive genetic testing or promote referral to genetics following negative CMA and/or Fragile X testing. Our data supports that ASD testing should include exome, CMA, and other clinically indicated tests, as first-tier tests, with the consideration of panel testing, in cases where exome sequencing is not an option. Lastly, our study helps to inform expectations for genetic testing yield by test type and patient presentation. En ligne : https://doi.org/10.1007/s10803-024-06423-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=566 [article] Implications of Provider Specialty, Test Type, and Demographic Factors on Genetic Testing Outcomes for Patients with Autism Spectrum Disorder [texte imprimé] / Caitlin N. HARRINGTON, Auteur ; Ana MORALES, Auteur ; Jonathan A. BERNSTEIN, Auteur ; Laurel CALDERWOOD, Auteur . - p.3231-3244. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 55-9 (September 2025) . - p.3231-3244 Index. décimale : PER Périodiques Résumé : A minority of patients with autism spectrum disorder (ASD) are offered genetic testing by their providers or referred for genetics evaluation despite published guidelines and consensus statements supporting genetics-informed care for this population. This study aimed to investigate the ordering habits of providers of different specialties and to additionally assess the diagnostic utility of genetic testing by test type, patient sex, and race and ethnicity. We retrospectively analyzed data associated with orders for the indication of ASD from a large clinical laboratory over 6 years (2017-2022). Geneticists and neurologists were more likely than other specialists to order exome sequencing and neurodevelopmental (NDD) panel testing while other providers were more likely to order chromosomal microarray (CMA) and Fragile X testing. Exome had the highest diagnostic yield (24.5%), followed by NDD panel (6.4%), CMA (6.2%), and Fragile X testing (0.4%). Females were 1.4x (95% CI: 1.2-1.7) more likely than males to receive a genetic diagnosis. However, for Fragile X, males had a higher diagnostic yield than females (0.4% vs 0.2%). Our findings highlight the need to enable non-genetics providers to order comprehensive genetic testing or promote referral to genetics following negative CMA and/or Fragile X testing. Our data supports that ASD testing should include exome, CMA, and other clinically indicated tests, as first-tier tests, with the consideration of panel testing, in cases where exome sequencing is not an option. Lastly, our study helps to inform expectations for genetic testing yield by test type and patient presentation. En ligne : https://doi.org/10.1007/s10803-024-06423-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=566

Parent-reported measure of repetitive behavior in Phelan-McDermid syndrome / Siddharth SRIVASTAVA in Journal of Neurodevelopmental Disorders, 13 (2021)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 13 (2021) Titre : Parent-reported measure of repetitive behavior in Phelan-McDermid syndrome Type de document : texte imprimé Auteurs : Siddharth SRIVASTAVA, Auteur ; Emma CONDY, Auteur ; Erin CARMODY, Auteur ; Rajna FILIP-DHIMA, Auteur ; Kush KAPUR, Auteur ; Jonathan A. BERNSTEIN, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Craig M. POWELL, Auteur ; Latha SOORYA, Auteur ; Audrey THURM, Auteur ; Joseph D. BUXBAUM, Auteur ; Mustafa SAHIN, Auteur ; A Lexander KOLEVZON, Auteur ; DEVELOPMENTAL SYNAPTOPATHIES CONSORTIUM, Auteur Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/psychology  Chromosome Deletion  Chromosome Disorders/complications  Chromosomes, Human, Pair 22  Cognition  Female  Humans  Parents  22q13 deletion  Autism  Intellectual disability  Repetitive behavior  Shank3  Stereotypy  client, Fortress Biotech), Novartis, ExpertConnect. KK is currently employed by  Alexion Pharmaceuticals, Inc. but completed this work while at Boston Children’s  Hospital. AK receives research support from AMO Pharma and consults to Ovid  Therapeutics, Acadia, and sema4. EBK has received funding from Seaside  Therapeutics, Novartis, Roche, Alcobra, Neuren, Cydan, Fulcrum, GW, Neurotrope,  Marinus, Zynerba, BioMarin, Ovid, Retrophin, AMO, Yamo, Acadia, Avexis, Ionis,  Ultragenyx, Lumos, GeneTx, and Vtesse/Sucampo/Mallinkcrodt Pharmaceuticals to  consult on trial design or development strategies and/or conduct clinical trials  in FXS or other NDDs or neurodegenerative disorders, and from Asuragen Inc to  develop testing standards for FMR1 testing. All funding to EBK is directed to  Rush University Medical Center to support rare disease programs. EBK receives no  personal funds. MS reports grant support from Novartis, Roche, Biogen, Astellas,  Aeovian, Bridgebio, Aucta and Quadrant Biosciences. He has served on Scientific  Advisory Boards for Roche, Celgene, Regenxbio, Alkermes, and Takeda. Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan McDermid syndrome (PMS) is a neurogenetic condition associated with a high prevalence of intellectual disability (ID) and autism spectrum disorder (ASD). This study provides a more comprehensive and quantitative profile of repetitive behaviors within the context of ID seen with the condition. METHODS: Individuals age 3-21 years with a confirmed PMS diagnosis participated in a multicenter observational study evaluating the phenotype and natural history of the disorder. We evaluated data collected from this study pertaining to repetitive behaviors from the Repetitive Behavior Scales-Revised (RBS-R). RESULTS: There were n = 90 participants who were part of this analysis. Forty-seven percent (n = 42/90) were female, and the average age at baseline evaluation was 8.88 ± 4.72 years. The mean best estimate IQ of the cohort was 26.08 ± 17.67 (range = 3.4-88), with n = 8 with mild ID (or no ID), n = 20 with moderate ID, and n = 62 with severe-profound ID. The RBS-R total overall score was 16.46 ± 13.9 (compared to 33.14 ± 20.60 reported in previous studies of ASD) (Lam and Aman, 2007), and the total number of items endorsed was 10.40 ± 6.81 (range = 0-29). After statistical correction for multiple comparisons, IQ correlated with the RBS-R stereotypic behavior subscale score (r(s) = - 0.33, unadjusted p = 0.0014, adjusted p = 0.01) and RBS-R stereotypic behavior total number of endorsed items (r(s) = - 0.32, unadjusted p = 0.0019, adjusted p = 0.01). IQ did not correlate with any other RBS-R subscale scores. CONCLUSIONS: The RBS-R total overall score in a PMS cohort appears milder compared to individuals with ASD characterized in previous studies. Stereotypic behavior in PMS may reflect cognitive functioning. En ligne : https://dx.doi.org/10.1186/s11689-021-09398-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Parent-reported measure of repetitive behavior in Phelan-McDermid syndrome [texte imprimé] / Siddharth SRIVASTAVA, Auteur ; Emma CONDY, Auteur ; Erin CARMODY, Auteur ; Rajna FILIP-DHIMA, Auteur ; Kush KAPUR, Auteur ; Jonathan A. BERNSTEIN, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Craig M. POWELL, Auteur ; Latha SOORYA, Auteur ; Audrey THURM, Auteur ; Joseph D. BUXBAUM, Auteur ; Mustafa SAHIN, Auteur ; A Lexander KOLEVZON, Auteur ; DEVELOPMENTAL SYNAPTOPATHIES CONSORTIUM, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 13 (2021) Mots-clés : Autism Spectrum Disorder/psychology  Chromosome Deletion  Chromosome Disorders/complications  Chromosomes, Human, Pair 22  Cognition  Female  Humans  Parents  22q13 deletion  Autism  Intellectual disability  Repetitive behavior  Shank3  Stereotypy  client, Fortress Biotech), Novartis, ExpertConnect. KK is currently employed by  Alexion Pharmaceuticals, Inc. but completed this work while at Boston Children’s  Hospital. AK receives research support from AMO Pharma and consults to Ovid  Therapeutics, Acadia, and sema4. EBK has received funding from Seaside  Therapeutics, Novartis, Roche, Alcobra, Neuren, Cydan, Fulcrum, GW, Neurotrope,  Marinus, Zynerba, BioMarin, Ovid, Retrophin, AMO, Yamo, Acadia, Avexis, Ionis,  Ultragenyx, Lumos, GeneTx, and Vtesse/Sucampo/Mallinkcrodt Pharmaceuticals to  consult on trial design or development strategies and/or conduct clinical trials  in FXS or other NDDs or neurodegenerative disorders, and from Asuragen Inc to  develop testing standards for FMR1 testing. All funding to EBK is directed to  Rush University Medical Center to support rare disease programs. EBK receives no  personal funds. MS reports grant support from Novartis, Roche, Biogen, Astellas,  Aeovian, Bridgebio, Aucta and Quadrant Biosciences. He has served on Scientific  Advisory Boards for Roche, Celgene, Regenxbio, Alkermes, and Takeda. Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan McDermid syndrome (PMS) is a neurogenetic condition associated with a high prevalence of intellectual disability (ID) and autism spectrum disorder (ASD). This study provides a more comprehensive and quantitative profile of repetitive behaviors within the context of ID seen with the condition. METHODS: Individuals age 3-21 years with a confirmed PMS diagnosis participated in a multicenter observational study evaluating the phenotype and natural history of the disorder. We evaluated data collected from this study pertaining to repetitive behaviors from the Repetitive Behavior Scales-Revised (RBS-R). RESULTS: There were n = 90 participants who were part of this analysis. Forty-seven percent (n = 42/90) were female, and the average age at baseline evaluation was 8.88 ± 4.72 years. The mean best estimate IQ of the cohort was 26.08 ± 17.67 (range = 3.4-88), with n = 8 with mild ID (or no ID), n = 20 with moderate ID, and n = 62 with severe-profound ID. The RBS-R total overall score was 16.46 ± 13.9 (compared to 33.14 ± 20.60 reported in previous studies of ASD) (Lam and Aman, 2007), and the total number of items endorsed was 10.40 ± 6.81 (range = 0-29). After statistical correction for multiple comparisons, IQ correlated with the RBS-R stereotypic behavior subscale score (r(s) = - 0.33, unadjusted p = 0.0014, adjusted p = 0.01) and RBS-R stereotypic behavior total number of endorsed items (r(s) = - 0.32, unadjusted p = 0.0019, adjusted p = 0.01). IQ did not correlate with any other RBS-R subscale scores. CONCLUSIONS: The RBS-R total overall score in a PMS cohort appears milder compared to individuals with ASD characterized in previous studies. Stereotypic behavior in PMS may reflect cognitive functioning. En ligne : https://dx.doi.org/10.1186/s11689-021-09398-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Protein-truncating variants and deletions of SHANK2 are associated with autism spectrum disorder and other neurodevelopmental concerns / Hailey SILVER in Journal of Neurodevelopmental Disorders, 17 (2025)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 17 (2025) Titre : Protein-truncating variants and deletions of SHANK2 are associated with autism spectrum disorder and other neurodevelopmental concerns Type de document : texte imprimé Auteurs : Hailey SILVER, Auteur ; Rori GREENBERG, Auteur ; Paige M. SIPER, Auteur ; Jessica ZWEIFACH, Auteur ; Renee SOUFER, Auteur ; Mustafa SAHIN, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Latha Valluripalli SOORYA, Auteur ; Audrey THURM, Auteur ; Jonathan A. BERNSTEIN, Auteur ; Alexander KOLEVZON, Auteur ; Dorothy E. GRICE, Auteur ; Joseph D. BUXBAUM, Auteur ; Tess LEVY, Auteur Langues : Anglais (eng) Mots-clés : Humans  Autism Spectrum Disorder/genetics/physiopathology  Male  Female  Nerve Tissue Proteins/genetics  Child  Child, Preschool  Chromosome Disorders/genetics/physiopathology  Developmental Disabilities/genetics/physiopathology  Adolescent  Attention Deficit Disorder with Hyperactivity/genetics  Intellectual Disability/genetics  Chromosomes, Human, Pair 22/genetics  Adult  Cohort Studies  Chromosome Deletion  Autism spectrum disorder  Developmental delay  Intellectual and developmental disability  Phenotype  SHANK2  Medicine at Mount Sinai’s Institutional Review Board (IRB) approved the study.  Caregivers or legal guardians of the participants provided informed consent, and  assent was obtained when applicable. Consent for publication: Not applicable.  Competing interests: A.K. receives research support from AMO Pharma and consults  for Acadia, Alkermes, Neuren, and GW Pharma. He serves on Scientific Advisory  Boards for Ovid Therapeutics, Jaguar Therapeutics, and Ritrova Therapeutics.  P.M.S. and Mount Sinai licensed the SAND developed by P.M.S. to Stoelting, Co.  J.D.B. holds a patent for IGF-1 in Phelan-McDermid syndrome, holds an honorary  professorship from Aarhus University Denmark, and is a journal editor for  Springer Nature. M.S. reports grant support from Biogen, Astellas, Neurvati  Neurosciences, Bridgebio, and Aucta. He has served on scientific advisory boards  for Neurogene, Jaguar Gene Therapy and Noema. EBK has received funding from  Seaside Therapeutics, Novartis, Roche, Alcobra, Neuren, Cydan, Fulcrum, GW,  Neurotrope, Marinus, Zynerba, BioMarin, Ovid, Retrophin, AMO, Yamo, Acadia,  Avexis, Ionis, Ultragenyx, Lumos, GeneTx, and Vtesse/Sucampo/Mallinkcrodt  Pharmaceuticals to consult on trial design or development strategies and/or  conduct clinical trials in FXS or other NDDs or neurodegenerative disorders, and  from Asuragen Inc to develop testing standards for FMR1 testing. All funding to  EBK is directed to Rush University Medical Center to support rare disease  programs. EBK receives no personal funds. The remaining authors declare that they  have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: SHANK2 disorder is a rare neurodevelopmental disorder caused by a deletion or pathogenic sequence variant of the SHANK2 gene and is associated with autism spectrum disorder (ASD), intellectual disability (ID), and developmental delay. To date, research in SHANK2 has focused on laboratory-based in vivo and in vitro studies with few prospective clinical studies in humans. METHODS: A remote assessment battery was comprised of caregiver interviews with a psychiatrist, psychologists, and a genetic counselor, caregiver-reports, and review of records. Results from this cohort were reported using descriptive statistics. An age-matched sample of participants with SHANK3 haploinsufficiency (Phelan-McDermid syndrome, PMS) was used to compare adaptive behavior between the two groups. RESULTS: All ten participants demonstrated delays in adaptive behavior, with most motor skills preserved and a weakness in communication. According to parent report, 90% of participants carried a formal diagnosis of ASD, 50% of participants carried a diagnosis of attention-deficit/hyperactivity disorder (ADHD), and mild-to-moderate developmental delays were noted. Sensory hyperreactivity and seeking behaviors were more pronounced than sensory hyporeactivity. Medical features included hypotonia, recurrent ear infections, and gastrointestinal abnormalities. No similar facial dysmorphic features were observed. Compared to PMS participants, individuals with SHANK2 disorder had significantly higher adaptive functioning. CONCLUSIONS: Consistent with previous studies of SHANK2 disorder, these results indicate mild to moderate developmental impairment. Overall, SHANK2 disorder is associated with developmental and adaptive functioning delays, high rates of autism, including sensory symptoms and repetitive behaviors, and ADHD. This study was limited by its remote nature, diverse age range, and the homogeneous racial and ethnic sample. Future studies should examine larger, diverse cohorts, add cognitive testing, capture longitudinal data, and include in-person assessments. En ligne : https://dx.doi.org/10.1186/s11689-025-09600-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 [article] Protein-truncating variants and deletions of SHANK2 are associated with autism spectrum disorder and other neurodevelopmental concerns [texte imprimé] / Hailey SILVER, Auteur ; Rori GREENBERG, Auteur ; Paige M. SIPER, Auteur ; Jessica ZWEIFACH, Auteur ; Renee SOUFER, Auteur ; Mustafa SAHIN, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Latha Valluripalli SOORYA, Auteur ; Audrey THURM, Auteur ; Jonathan A. BERNSTEIN, Auteur ; Alexander KOLEVZON, Auteur ; Dorothy E. GRICE, Auteur ; Joseph D. BUXBAUM, Auteur ; Tess LEVY, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 17 (2025) Mots-clés : Humans  Autism Spectrum Disorder/genetics/physiopathology  Male  Female  Nerve Tissue Proteins/genetics  Child  Child, Preschool  Chromosome Disorders/genetics/physiopathology  Developmental Disabilities/genetics/physiopathology  Adolescent  Attention Deficit Disorder with Hyperactivity/genetics  Intellectual Disability/genetics  Chromosomes, Human, Pair 22/genetics  Adult  Cohort Studies  Chromosome Deletion  Autism spectrum disorder  Developmental delay  Intellectual and developmental disability  Phenotype  SHANK2  Medicine at Mount Sinai’s Institutional Review Board (IRB) approved the study.  Caregivers or legal guardians of the participants provided informed consent, and  assent was obtained when applicable. Consent for publication: Not applicable.  Competing interests: A.K. receives research support from AMO Pharma and consults  for Acadia, Alkermes, Neuren, and GW Pharma. He serves on Scientific Advisory  Boards for Ovid Therapeutics, Jaguar Therapeutics, and Ritrova Therapeutics.  P.M.S. and Mount Sinai licensed the SAND developed by P.M.S. to Stoelting, Co.  J.D.B. holds a patent for IGF-1 in Phelan-McDermid syndrome, holds an honorary  professorship from Aarhus University Denmark, and is a journal editor for  Springer Nature. M.S. reports grant support from Biogen, Astellas, Neurvati  Neurosciences, Bridgebio, and Aucta. He has served on scientific advisory boards  for Neurogene, Jaguar Gene Therapy and Noema. EBK has received funding from  Seaside Therapeutics, Novartis, Roche, Alcobra, Neuren, Cydan, Fulcrum, GW,  Neurotrope, Marinus, Zynerba, BioMarin, Ovid, Retrophin, AMO, Yamo, Acadia,  Avexis, Ionis, Ultragenyx, Lumos, GeneTx, and Vtesse/Sucampo/Mallinkcrodt  Pharmaceuticals to consult on trial design or development strategies and/or  conduct clinical trials in FXS or other NDDs or neurodegenerative disorders, and  from Asuragen Inc to develop testing standards for FMR1 testing. All funding to  EBK is directed to Rush University Medical Center to support rare disease  programs. EBK receives no personal funds. The remaining authors declare that they  have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: SHANK2 disorder is a rare neurodevelopmental disorder caused by a deletion or pathogenic sequence variant of the SHANK2 gene and is associated with autism spectrum disorder (ASD), intellectual disability (ID), and developmental delay. To date, research in SHANK2 has focused on laboratory-based in vivo and in vitro studies with few prospective clinical studies in humans. METHODS: A remote assessment battery was comprised of caregiver interviews with a psychiatrist, psychologists, and a genetic counselor, caregiver-reports, and review of records. Results from this cohort were reported using descriptive statistics. An age-matched sample of participants with SHANK3 haploinsufficiency (Phelan-McDermid syndrome, PMS) was used to compare adaptive behavior between the two groups. RESULTS: All ten participants demonstrated delays in adaptive behavior, with most motor skills preserved and a weakness in communication. According to parent report, 90% of participants carried a formal diagnosis of ASD, 50% of participants carried a diagnosis of attention-deficit/hyperactivity disorder (ADHD), and mild-to-moderate developmental delays were noted. Sensory hyperreactivity and seeking behaviors were more pronounced than sensory hyporeactivity. Medical features included hypotonia, recurrent ear infections, and gastrointestinal abnormalities. No similar facial dysmorphic features were observed. Compared to PMS participants, individuals with SHANK2 disorder had significantly higher adaptive functioning. CONCLUSIONS: Consistent with previous studies of SHANK2 disorder, these results indicate mild to moderate developmental impairment. Overall, SHANK2 disorder is associated with developmental and adaptive functioning delays, high rates of autism, including sensory symptoms and repetitive behaviors, and ADHD. This study was limited by its remote nature, diverse age range, and the homogeneous racial and ethnic sample. Future studies should examine larger, diverse cohorts, add cognitive testing, capture longitudinal data, and include in-person assessments. En ligne : https://dx.doi.org/10.1186/s11689-025-09600-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576

Psychometric Study of the Social Responsiveness Scale in Phelan-McDermid Syndrome / Kellie GERGOUDIS in Autism Research, 13-8 (August 2020)  

Public ISBD [article]  inAutism Research > 13-8 (August 2020) . - p.1383-1396 Titre : Psychometric Study of the Social Responsiveness Scale in Phelan-McDermid Syndrome Type de document : texte imprimé Auteurs : Kellie GERGOUDIS, Auteur ; Alan WEINBERG, Auteur ; Jonathan TEMPLIN, Auteur ; Cristan FARMER, Auteur ; Allison DURKIN, Auteur ; Jordana WEISSMAN, Auteur ; Paige SIPER, Auteur ; Jennifer H. FOSS-FEIG, Auteur ; Maria Del Pilar TRELLES, Auteur ; Jonathan A. BERNSTEIN, Auteur ; Joseph D. BUXBAUM, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Craig M. POWELL, Auteur ; Mustafa SAHIN, Auteur ; Latha SOORYA, Auteur ; Audrey THURM, Auteur ; Alexander KOLEVZON, Auteur Article en page(s) : p.1383-1396 Langues : Anglais (eng) Mots-clés : Item Response Theory  Phelan-McDermid syndrome  autism spectrum disorder  behavioral measures  intellectual disability Index. décimale : PER Périodiques Résumé : The Social Responsiveness Scale-2 (SRS-2) is a quantitative measure used to characterize symptoms of autism spectrum disorder (ASD). However, research suggests that SRS-2 scores are significantly influenced by language ability and intellectual disability (ID). Efforts to refine the SRS-2 by Sturm, Kuhfeld, Kasari, and Mccracken [Journal of Child Psychology and Psychiatry, 58(9), 1053-1061] yielded a shortened form, yet its psychometric properties in populations with severe ID remain unknown. This study aims to examine the psychometric properties of the SRS-2 in Phelan-McDermid syndrome (PMS), a genetic condition associated with ASD and ID, thereby guiding score interpretation in this population and future development of targeted scales. Analyses, including Item Response Theory (IRT), were conducted on a sample of individuals with PMS (n = 91) recruited at six sites nationally. Psychometric properties evaluated include measures of reliability (internal consistency, test-retest reliability) and validity (structural, construct, content). While both SRS-2 forms are reliable, the shortened SRS-2 shows superior validity to the full SRS-2 for measuring ASD symptoms in PMS. On IRT analysis, the shortened SRS-2 shows excellent discrimination and precisely evaluates respondents across a wide range of ASD symptomatology but interpretation is limited by uncertain content validity and small sample size. The shortened SRS-2 shows some promise for use in PMS, but future refinements and additions are needed to develop items that are tailored to identify ASD in children with severe ID and specifically PMS. LAY SUMMARY: This study determined that a shortened form of the Social Responsiveness Scale, Second Edition (SRS-2) shows both promise and limitations for the characterization of autism symptomatology in individuals with Phelan-McDermid syndrome (PMS), a population characterized by intellectual disability (ID). Caution should be used when interpreting SRS-2 scores in individuals with ID and future research should modify existing items and develop new items to improve the SRS-2's ability to accurately characterize autism symptomatology in PMS. Autism Res 2020, 13: 1383-1396. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.2299 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=430 [article] Psychometric Study of the Social Responsiveness Scale in Phelan-McDermid Syndrome [texte imprimé] / Kellie GERGOUDIS, Auteur ; Alan WEINBERG, Auteur ; Jonathan TEMPLIN, Auteur ; Cristan FARMER, Auteur ; Allison DURKIN, Auteur ; Jordana WEISSMAN, Auteur ; Paige SIPER, Auteur ; Jennifer H. FOSS-FEIG, Auteur ; Maria Del Pilar TRELLES, Auteur ; Jonathan A. BERNSTEIN, Auteur ; Joseph D. BUXBAUM, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Craig M. POWELL, Auteur ; Mustafa SAHIN, Auteur ; Latha SOORYA, Auteur ; Audrey THURM, Auteur ; Alexander KOLEVZON, Auteur . - p.1383-1396. Langues : Anglais (eng) in Autism Research > 13-8 (August 2020) . - p.1383-1396 Mots-clés : Item Response Theory  Phelan-McDermid syndrome  autism spectrum disorder  behavioral measures  intellectual disability Index. décimale : PER Périodiques Résumé : The Social Responsiveness Scale-2 (SRS-2) is a quantitative measure used to characterize symptoms of autism spectrum disorder (ASD). However, research suggests that SRS-2 scores are significantly influenced by language ability and intellectual disability (ID). Efforts to refine the SRS-2 by Sturm, Kuhfeld, Kasari, and Mccracken [Journal of Child Psychology and Psychiatry, 58(9), 1053-1061] yielded a shortened form, yet its psychometric properties in populations with severe ID remain unknown. This study aims to examine the psychometric properties of the SRS-2 in Phelan-McDermid syndrome (PMS), a genetic condition associated with ASD and ID, thereby guiding score interpretation in this population and future development of targeted scales. Analyses, including Item Response Theory (IRT), were conducted on a sample of individuals with PMS (n = 91) recruited at six sites nationally. Psychometric properties evaluated include measures of reliability (internal consistency, test-retest reliability) and validity (structural, construct, content). While both SRS-2 forms are reliable, the shortened SRS-2 shows superior validity to the full SRS-2 for measuring ASD symptoms in PMS. On IRT analysis, the shortened SRS-2 shows excellent discrimination and precisely evaluates respondents across a wide range of ASD symptomatology but interpretation is limited by uncertain content validity and small sample size. The shortened SRS-2 shows some promise for use in PMS, but future refinements and additions are needed to develop items that are tailored to identify ASD in children with severe ID and specifically PMS. LAY SUMMARY: This study determined that a shortened form of the Social Responsiveness Scale, Second Edition (SRS-2) shows both promise and limitations for the characterization of autism symptomatology in individuals with Phelan-McDermid syndrome (PMS), a population characterized by intellectual disability (ID). Caution should be used when interpreting SRS-2 scores in individuals with ID and future research should modify existing items and develop new items to improve the SRS-2's ability to accurately characterize autism symptomatology in PMS. Autism Res 2020, 13: 1383-1396. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.2299 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=430

What Role Does Comparative Genomic Hybridization (CGH) Play in ASC? / Jonathan A. BERNSTEIN

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