16 recherche sur le mot-clé 'Chromosome Deletion'

Developmental milestones and cognitive trajectories in school-aged children with 16p11.2 deletion / Jente VERBESSELT in Journal of Neurodevelopmental Disorders, 17 (2025)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 17 (2025) Titre : Developmental milestones and cognitive trajectories in school-aged children with 16p11.2 deletion Type de document : texte imprimé Auteurs : Jente VERBESSELT, Auteur ; Jeroen BRECKPOT, Auteur ; Inge ZINK, Auteur ; Ann SWILLEN, Auteur Langues : Anglais (eng) Mots-clés : Humans  Child  Adolescent  Female  Male  Chromosomes, Human, Pair 16/genetics  Child, Preschool  Intellectual Disability/physiopathology/genetics  Longitudinal Studies  Chromosome Deletion  Chromosome Disorders/physiopathology/complications/genetics  Intelligence  Cognition/physiology  Child Development/physiology  Developmental Disabilities/genetics/physiopathology  Fecal Incontinence/physiopathology  Intelligence Tests  Autistic Disorder  16p11.2 deletion syndrome  Cognition  Copy number variants  Deep phenotyping  Developmental trajectories  Early development  in accordance with the Declaration of Helsinki and approved by the Ethics  Committee Research of University Hospitals Leuven (protocol code S54485, 6  December 2012 and 26 March 2021). Patients and their parents were directly  informed about the aims of the research project, and all participants signed  informed consent. Consent for publication: Not applicable. Competing interests:  The authors declare no conflict of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: 16p11.2 deletion syndrome (16p11.2DS) is a recurrent CNV that occurs de novo in approximately 70% of cases and confers risk for neurodevelopmental disorders, including intellectual disability (ID) and autism spectrum disorders (ASD). The current study focusses on developmental milestones, cognitive profiles and longitudinal cognitive trajectories. METHODS: In-person assessments, digital medical records and parental interviews on developmental history of 24 children (5-16 years) with a confirmed BP4-BP5 16p11.2DS were reviewed and analysed for developmental milestones (motor, language, continence). Standardised intelligence tests were administered in all children, and longitudinal IQ-data were available for a subgroup (79%, 19/24). RESULTS: Motor, language, and continence milestones were delayed. Average IQ was in the borderline range (IQ 71) with 46% (11/24) having borderline IQ (IQ 70-84). Both intra- and interindividual variability were found across the five cognitive domains with significant discrepancies between verbal and non-verbal skills in 55% (11/20). Longitudinal IQ-data indicate that school-aged children with 16p11.2DS perform statistically significantly lower at the second time point (p < 0.001) with 58% showing a growing into deficit trajectory. CONCLUSION: Delayed motor, language and continence milestones are common in 16p11.2DS carriers. School-aged children with 16p11.2DS show increasing cognitive impairments over time, pointing to the need for early diagnosis, regular cognitive follow-up and individualised intervention. The high prevalence of disharmonic IQ-profiles highlights the importance of expanding the focus beyond full-scale IQ (FSIQ) outcomes. Future studies in larger cohorts including carrier relatives are needed to gain more insight into the penetrance and phenotypic variability of 16p11.2DS. En ligne : https://dx.doi.org/10.1186/s11689-025-09615-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 [article] Developmental milestones and cognitive trajectories in school-aged children with 16p11.2 deletion [texte imprimé] / Jente VERBESSELT, Auteur ; Jeroen BRECKPOT, Auteur ; Inge ZINK, Auteur ; Ann SWILLEN, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 17 (2025) Mots-clés : Humans  Child  Adolescent  Female  Male  Chromosomes, Human, Pair 16/genetics  Child, Preschool  Intellectual Disability/physiopathology/genetics  Longitudinal Studies  Chromosome Deletion  Chromosome Disorders/physiopathology/complications/genetics  Intelligence  Cognition/physiology  Child Development/physiology  Developmental Disabilities/genetics/physiopathology  Fecal Incontinence/physiopathology  Intelligence Tests  Autistic Disorder  16p11.2 deletion syndrome  Cognition  Copy number variants  Deep phenotyping  Developmental trajectories  Early development  in accordance with the Declaration of Helsinki and approved by the Ethics  Committee Research of University Hospitals Leuven (protocol code S54485, 6  December 2012 and 26 March 2021). Patients and their parents were directly  informed about the aims of the research project, and all participants signed  informed consent. Consent for publication: Not applicable. Competing interests:  The authors declare no conflict of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: 16p11.2 deletion syndrome (16p11.2DS) is a recurrent CNV that occurs de novo in approximately 70% of cases and confers risk for neurodevelopmental disorders, including intellectual disability (ID) and autism spectrum disorders (ASD). The current study focusses on developmental milestones, cognitive profiles and longitudinal cognitive trajectories. METHODS: In-person assessments, digital medical records and parental interviews on developmental history of 24 children (5-16 years) with a confirmed BP4-BP5 16p11.2DS were reviewed and analysed for developmental milestones (motor, language, continence). Standardised intelligence tests were administered in all children, and longitudinal IQ-data were available for a subgroup (79%, 19/24). RESULTS: Motor, language, and continence milestones were delayed. Average IQ was in the borderline range (IQ 71) with 46% (11/24) having borderline IQ (IQ 70-84). Both intra- and interindividual variability were found across the five cognitive domains with significant discrepancies between verbal and non-verbal skills in 55% (11/20). Longitudinal IQ-data indicate that school-aged children with 16p11.2DS perform statistically significantly lower at the second time point (p < 0.001) with 58% showing a growing into deficit trajectory. CONCLUSION: Delayed motor, language and continence milestones are common in 16p11.2DS carriers. School-aged children with 16p11.2DS show increasing cognitive impairments over time, pointing to the need for early diagnosis, regular cognitive follow-up and individualised intervention. The high prevalence of disharmonic IQ-profiles highlights the importance of expanding the focus beyond full-scale IQ (FSIQ) outcomes. Future studies in larger cohorts including carrier relatives are needed to gain more insight into the penetrance and phenotypic variability of 16p11.2DS. En ligne : https://dx.doi.org/10.1186/s11689-025-09615-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576

Phenotypic variation in neural sensory processing by deletion size, age, and sex in Phelan-McDermid syndrome / Melody Reese SMITH in Journal of Neurodevelopmental Disorders, 17 (2025)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 17 (2025) Titre : Phenotypic variation in neural sensory processing by deletion size, age, and sex in Phelan-McDermid syndrome Type de document : texte imprimé Auteurs : Melody Reese SMITH, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Andrew THALIATH, Auteur ; Emily L. ISENSTEIN, Auteur ; Allison R. DURKIN, Auteur ; Jennifer FOSS-FEIG, Auteur ; Paige M. SIPER, Auteur ; Charles A. NELSON, Auteur ; Lauren BACZEWSKI, Auteur ; April R. LEVIN, Auteur ; Craig M. POWELL, Auteur ; Stormi L. PULVER, Auteur ; Matthew W. MOSCONI, Auteur ; Alexander KOLEVZON, Auteur ; Lauren E. ETHRIDGE, Auteur Langues : Anglais (eng) Mots-clés : Humans  Female  Male  Adolescent  Child  Electroencephalography  Chromosomes, Human, Pair 22/genetics  Chromosome Disorders/physiopathology/genetics  Chromosome Deletion  Phenotype  Evoked Potentials/physiology  Age Factors  Sensory Gating/physiology  Acoustic Stimulation  Brain/physiopathology  Evoked Potentials, Auditory/physiology  Auditory Perception/physiology  Sex Factors Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid Syndrome (PMS) is a rare genetic condition characterized by deletion or mutation of region 22q13.3, which includes the SHANK3 gene. Clinical descriptions of this population include severely impaired or absent expressive language, mildly dysmorphic features, neonatal hypotonia, developmental delays, intellectual impairments, and autistic-like traits including abnormal reactivity to sensory stimuli. Electroencephalography (EEG) has shown promise as a tool for identifying neurophysiological abnormalities in neurodevelopmental disorders. However, few EEG studies focused on sensory processing have been performed on this population. Thus, this study focuses on comparisons of event-related potential (ERP), event-related spectral perturbation (ERSP), and inter-trial coherence (ITC) between PMS and typically developing (TD) individuals in a standard auditory gating task measuring attenuation of neural activity to repetitive auditory stimuli. METHODS: A total of 37 participants, 21 PMS (12 females, age range 8-18.6 years) and 16 TD individuals (8 females, age range 8.2-15.3 years) were included. Analysis consisted of a series of general linear models using a regional (frontal) and global (whole-head) approach to characterize neural activity between PMS and TD participants by age, sex, and group. RESULTS: Most notably, individuals with PMS had delayed or low amplitude P50, N1, and P2 responses in frontal and whole-head analyses as well as poor frontal phase-locking to auditory stimuli for alpha, beta and gamma ITC, indicating impaired processing of stimulus properties. Additionally, individuals with PMS differed from TD by age in delta, theta, and alpha power, as well as frontal beta-gamma ITC, suggesting different developmental trajectories for individuals with PMS. Within PMS, larger deletion sizes were associated with increased auditory processing abnormalities for frontal P50 as well as whole-head P50 and N1. LIMITATIONS: This is one of the largest EEG studies of PMS. However, PMS is a rare genetic condition, and our small sample has limited statistical power for subgroup comparisons. Findings should be considered exploratory. CONCLUSIONS: Results suggest that participants with PMS exhibit auditory processing abnormalities with complex variation by deletion-size, age, and sex with congruency to impaired early recognition (P50), feature processing (N1), information integration (delta, theta), sensory processing and auditory inhibition (alpha), and inhibitory modulation of repeated auditory stimuli (beta, gamma). Findings may provide valuable insight into clinical characterization of sensory and speech behaviors in future studies. En ligne : https://dx.doi.org/10.1186/s11689-025-09642-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 [article] Phenotypic variation in neural sensory processing by deletion size, age, and sex in Phelan-McDermid syndrome [texte imprimé] / Melody Reese SMITH, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Andrew THALIATH, Auteur ; Emily L. ISENSTEIN, Auteur ; Allison R. DURKIN, Auteur ; Jennifer FOSS-FEIG, Auteur ; Paige M. SIPER, Auteur ; Charles A. NELSON, Auteur ; Lauren BACZEWSKI, Auteur ; April R. LEVIN, Auteur ; Craig M. POWELL, Auteur ; Stormi L. PULVER, Auteur ; Matthew W. MOSCONI, Auteur ; Alexander KOLEVZON, Auteur ; Lauren E. ETHRIDGE, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 17 (2025) Mots-clés : Humans  Female  Male  Adolescent  Child  Electroencephalography  Chromosomes, Human, Pair 22/genetics  Chromosome Disorders/physiopathology/genetics  Chromosome Deletion  Phenotype  Evoked Potentials/physiology  Age Factors  Sensory Gating/physiology  Acoustic Stimulation  Brain/physiopathology  Evoked Potentials, Auditory/physiology  Auditory Perception/physiology  Sex Factors Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid Syndrome (PMS) is a rare genetic condition characterized by deletion or mutation of region 22q13.3, which includes the SHANK3 gene. Clinical descriptions of this population include severely impaired or absent expressive language, mildly dysmorphic features, neonatal hypotonia, developmental delays, intellectual impairments, and autistic-like traits including abnormal reactivity to sensory stimuli. Electroencephalography (EEG) has shown promise as a tool for identifying neurophysiological abnormalities in neurodevelopmental disorders. However, few EEG studies focused on sensory processing have been performed on this population. Thus, this study focuses on comparisons of event-related potential (ERP), event-related spectral perturbation (ERSP), and inter-trial coherence (ITC) between PMS and typically developing (TD) individuals in a standard auditory gating task measuring attenuation of neural activity to repetitive auditory stimuli. METHODS: A total of 37 participants, 21 PMS (12 females, age range 8-18.6 years) and 16 TD individuals (8 females, age range 8.2-15.3 years) were included. Analysis consisted of a series of general linear models using a regional (frontal) and global (whole-head) approach to characterize neural activity between PMS and TD participants by age, sex, and group. RESULTS: Most notably, individuals with PMS had delayed or low amplitude P50, N1, and P2 responses in frontal and whole-head analyses as well as poor frontal phase-locking to auditory stimuli for alpha, beta and gamma ITC, indicating impaired processing of stimulus properties. Additionally, individuals with PMS differed from TD by age in delta, theta, and alpha power, as well as frontal beta-gamma ITC, suggesting different developmental trajectories for individuals with PMS. Within PMS, larger deletion sizes were associated with increased auditory processing abnormalities for frontal P50 as well as whole-head P50 and N1. LIMITATIONS: This is one of the largest EEG studies of PMS. However, PMS is a rare genetic condition, and our small sample has limited statistical power for subgroup comparisons. Findings should be considered exploratory. CONCLUSIONS: Results suggest that participants with PMS exhibit auditory processing abnormalities with complex variation by deletion-size, age, and sex with congruency to impaired early recognition (P50), feature processing (N1), information integration (delta, theta), sensory processing and auditory inhibition (alpha), and inhibitory modulation of repeated auditory stimuli (beta, gamma). Findings may provide valuable insight into clinical characterization of sensory and speech behaviors in future studies. En ligne : https://dx.doi.org/10.1186/s11689-025-09642-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576

Sensory processing in 16p11.2 deletion and 16p11.2 duplication / Harriet SMITH in Autism Research, 15-11 (November 2022)  

Public ISBD [article]  inAutism Research > 15-11 (November 2022) . - p.2081-2098 Titre : Sensory processing in 16p11.2 deletion and 16p11.2 duplication Type de document : texte imprimé Auteurs : Harriet SMITH, Auteur ; Chloe LANE, Auteur ; Reem AL-JAWAHIRI, Auteur ; Megan FREETH, Auteur Article en page(s) : p.2081-2098 Langues : Anglais (eng) Mots-clés : Child  Humans  Chromosome Deletion  Autism Spectrum Disorder/genetics  Autistic Disorder/genetics  Intellectual Disability/genetics  Perception  Chromosomes, Human, Pair 16/genetics  Chromosome Disorders/complications/genetics  Adhd  anxiety  autistic  sensory processing  sensory systems Index. décimale : PER Périodiques Résumé : Deletions and duplications at the chromosomal region of 16p11.2 have a broad range of phenotypic effects including increased likelihood of intellectual disability, autism, attention deficit hyperactivity disorder (ADHD), epilepsy, and language and motor delays. However, whether and how sensory processing is affected has not yet been considered in detail. Parents/caregivers of 38 children with a 16p11.2 deletion and 31 children with a 16p11.2 duplication completed the Sensory Behavior Questionnaire (SBQ) and the Child Sensory Profile 2 (CSP-2) along with other standardized questionnaires assessing autistic traits (SRS-2), ADHD traits (Conners 3), anxiety (SCAS-P) and adaptive behavior (VABS-3). SBQ and CSP-2 responses found that sensory processing differences were clearly evident in both 16p11.2 deletion and 16p11.2 duplication, though there was significant variation in both cohorts. SBQ data indicated the frequency and impact of sensory behavior were more severe when compared to neurotypical children, with levels being similar to autistic children. CSP-2 data indicated over 70% of children displayed clear differences in sensory registration (missing sensory input). Seventy-one percent with 16p11.2 duplications were also unusually sensitive to sensory information and 57% with 16p11.2 duplications were unusually avoidant of sensory stimuli. This first detailed assessment of sensory processing, alongside other clinical features, in relatively large cohorts of children with a 16p11.2 deletion and 16p11.2 duplication demonstrates that sensory processing differences have a profound impact on their lives. En ligne : http://dx.doi.org/10.1002/aur.2802 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=488 [article] Sensory processing in 16p11.2 deletion and 16p11.2 duplication [texte imprimé] / Harriet SMITH, Auteur ; Chloe LANE, Auteur ; Reem AL-JAWAHIRI, Auteur ; Megan FREETH, Auteur . - p.2081-2098. Langues : Anglais (eng) in Autism Research > 15-11 (November 2022) . - p.2081-2098 Mots-clés : Child  Humans  Chromosome Deletion  Autism Spectrum Disorder/genetics  Autistic Disorder/genetics  Intellectual Disability/genetics  Perception  Chromosomes, Human, Pair 16/genetics  Chromosome Disorders/complications/genetics  Adhd  anxiety  autistic  sensory processing  sensory systems Index. décimale : PER Périodiques Résumé : Deletions and duplications at the chromosomal region of 16p11.2 have a broad range of phenotypic effects including increased likelihood of intellectual disability, autism, attention deficit hyperactivity disorder (ADHD), epilepsy, and language and motor delays. However, whether and how sensory processing is affected has not yet been considered in detail. Parents/caregivers of 38 children with a 16p11.2 deletion and 31 children with a 16p11.2 duplication completed the Sensory Behavior Questionnaire (SBQ) and the Child Sensory Profile 2 (CSP-2) along with other standardized questionnaires assessing autistic traits (SRS-2), ADHD traits (Conners 3), anxiety (SCAS-P) and adaptive behavior (VABS-3). SBQ and CSP-2 responses found that sensory processing differences were clearly evident in both 16p11.2 deletion and 16p11.2 duplication, though there was significant variation in both cohorts. SBQ data indicated the frequency and impact of sensory behavior were more severe when compared to neurotypical children, with levels being similar to autistic children. CSP-2 data indicated over 70% of children displayed clear differences in sensory registration (missing sensory input). Seventy-one percent with 16p11.2 duplications were also unusually sensitive to sensory information and 57% with 16p11.2 duplications were unusually avoidant of sensory stimuli. This first detailed assessment of sensory processing, alongside other clinical features, in relatively large cohorts of children with a 16p11.2 deletion and 16p11.2 duplication demonstrates that sensory processing differences have a profound impact on their lives. En ligne : http://dx.doi.org/10.1002/aur.2802 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=488

Clinical, developmental and serotonemia phenotyping of a sample of 70 Italian patients with Phelan-McDermid Syndrome / Lisa ASTA in Journal of Neurodevelopmental Disorders, 16 (2024)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 16 (2024) Titre : Clinical, developmental and serotonemia phenotyping of a sample of 70 Italian patients with Phelan-McDermid Syndrome Type de document : texte imprimé Auteurs : Lisa ASTA, Auteur ; Arianna RICCIARDELLO, Auteur ; Francesca CUCINOTTA, Auteur ; Laura TURRIZIANI, Auteur ; Maria BONCODDO, Auteur ; Fabiana BELLOMO, Auteur ; Jessica ANGELINI, Auteur ; Martina GNAZZO, Auteur ; Giulia SCANDOLO, Auteur ; Giulia PISANÃ’, Auteur ; Francesco PELAGATTI, Auteur ; Fethia CHEHBANI, Auteur ; Michela CAMIA, Auteur ; Antonio M. PERSICO, Auteur Langues : Anglais (eng) Mots-clés : Humans  Male  Female  Italy  Phenotype  Child  Chromosome Deletion  Chromosomes, Human, Pair 22/genetics  Adolescent  Child, Preschool  Adult  Young Adult  Chromosome Disorders/physiopathology/complications/blood  Autism Spectrum Disorder/blood/physiopathology/complications  Nerve Tissue Proteins/blood/genetics  Intellectual Disability/etiology/blood  Shank3  22q13 deletion syndrome  Autism spectrum disorder  Hyperserotonemia  Intellectual disability  Macrocephaly  Neuroinflammation  Phelan-McDermid syndrome  Serotonin Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is caused by monoallelic loss or inactivation at the SHANK3 gene, located in human chr 22q13.33, and is often associated with Autism Spectrum Disorder (ASD). OBJECTIVES: To assess the clinical and developmental phenotype in a novel sample of PMS patients, including for the first time auxometric trajectories and serotonin blood levels. METHODS: 70 Italian PMS patients were clinically characterized by parental report, direct medical observation, and a thorough medical and psychodiagnostic protocol. Serotonin levels were measured in platelet-rich plasma by HPLC. RESULTS: Our sample includes 59 (84.3%) cases with chr. 22q13 terminal deletion, 5 (7.1%) disruptive SHANK3 mutations, and 6 (8.6%) ring chromosome 22. Intellectual disability was present in 69 (98.6%) cases, motor coordination disorder in 65 (92.9%), ASD in 20 (28.6%), and lifetime bipolar disorder in 12 (17.1%). Prenatal and postnatal complications were frequent (22.9%-48.6%). Expressive and receptive language were absent in 49 (70.0%) and 19 (27.1%) cases, respectively. Decreased pain sensitivity was reported in 56 (80.0%), hyperactivity in 49 (80.3%), abnormal sleep in 45 (64.3%), congenital dysmorphisms in 35 (58.3%), chronic stool abnormalities and especially constipation in 29 (41.4%). Parents reported noticing behavioral abnormalities during early childhood immediately after an infective episode in 34 (48.6%) patients. Brain MRI anomalies were observed in 53 (79.1%), EEG abnormalities in 16 (23.5%), kidney and upper urinary tract malformations in 18 (28.1%). Two novel phenotypes emerged: (a) a subgroup of 12/44 (27.3%) PMS patients displays smaller head size at enrollment (mean age 11.8 yrs) compared to their first year of neonatal life, documenting a deceleration of head growth (p < 0.001); (b) serotonin blood levels are significantly lower in 21 PMS patients compared to their 21 unaffected siblings (P < 0.05), and to 432 idiopathic ASD cases (p < 0.001). CONCLUSIONS: We replicate and extend the description of many phenotypic characteristics present in PMS, and report two novel features: (1) growth trajectories are variable and head growth appears to slow down during childhood in some PMS patients; (2) serotonin blood levels are decreased in PMS, and not increased as frequently occurs in ASD. Further investigations of these novel features are under way. En ligne : https://dx.doi.org/10.1186/s11689-024-09572-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 [article] Clinical, developmental and serotonemia phenotyping of a sample of 70 Italian patients with Phelan-McDermid Syndrome [texte imprimé] / Lisa ASTA, Auteur ; Arianna RICCIARDELLO, Auteur ; Francesca CUCINOTTA, Auteur ; Laura TURRIZIANI, Auteur ; Maria BONCODDO, Auteur ; Fabiana BELLOMO, Auteur ; Jessica ANGELINI, Auteur ; Martina GNAZZO, Auteur ; Giulia SCANDOLO, Auteur ; Giulia PISANÃ’, Auteur ; Francesco PELAGATTI, Auteur ; Fethia CHEHBANI, Auteur ; Michela CAMIA, Auteur ; Antonio M. PERSICO, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 16 (2024) Mots-clés : Humans  Male  Female  Italy  Phenotype  Child  Chromosome Deletion  Chromosomes, Human, Pair 22/genetics  Adolescent  Child, Preschool  Adult  Young Adult  Chromosome Disorders/physiopathology/complications/blood  Autism Spectrum Disorder/blood/physiopathology/complications  Nerve Tissue Proteins/blood/genetics  Intellectual Disability/etiology/blood  Shank3  22q13 deletion syndrome  Autism spectrum disorder  Hyperserotonemia  Intellectual disability  Macrocephaly  Neuroinflammation  Phelan-McDermid syndrome  Serotonin Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is caused by monoallelic loss or inactivation at the SHANK3 gene, located in human chr 22q13.33, and is often associated with Autism Spectrum Disorder (ASD). OBJECTIVES: To assess the clinical and developmental phenotype in a novel sample of PMS patients, including for the first time auxometric trajectories and serotonin blood levels. METHODS: 70 Italian PMS patients were clinically characterized by parental report, direct medical observation, and a thorough medical and psychodiagnostic protocol. Serotonin levels were measured in platelet-rich plasma by HPLC. RESULTS: Our sample includes 59 (84.3%) cases with chr. 22q13 terminal deletion, 5 (7.1%) disruptive SHANK3 mutations, and 6 (8.6%) ring chromosome 22. Intellectual disability was present in 69 (98.6%) cases, motor coordination disorder in 65 (92.9%), ASD in 20 (28.6%), and lifetime bipolar disorder in 12 (17.1%). Prenatal and postnatal complications were frequent (22.9%-48.6%). Expressive and receptive language were absent in 49 (70.0%) and 19 (27.1%) cases, respectively. Decreased pain sensitivity was reported in 56 (80.0%), hyperactivity in 49 (80.3%), abnormal sleep in 45 (64.3%), congenital dysmorphisms in 35 (58.3%), chronic stool abnormalities and especially constipation in 29 (41.4%). Parents reported noticing behavioral abnormalities during early childhood immediately after an infective episode in 34 (48.6%) patients. Brain MRI anomalies were observed in 53 (79.1%), EEG abnormalities in 16 (23.5%), kidney and upper urinary tract malformations in 18 (28.1%). Two novel phenotypes emerged: (a) a subgroup of 12/44 (27.3%) PMS patients displays smaller head size at enrollment (mean age 11.8 yrs) compared to their first year of neonatal life, documenting a deceleration of head growth (p < 0.001); (b) serotonin blood levels are significantly lower in 21 PMS patients compared to their 21 unaffected siblings (P < 0.05), and to 432 idiopathic ASD cases (p < 0.001). CONCLUSIONS: We replicate and extend the description of many phenotypic characteristics present in PMS, and report two novel features: (1) growth trajectories are variable and head growth appears to slow down during childhood in some PMS patients; (2) serotonin blood levels are decreased in PMS, and not increased as frequently occurs in ASD. Further investigations of these novel features are under way. En ligne : https://dx.doi.org/10.1186/s11689-024-09572-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576

Psychotic symptoms in 16p11.2 copy-number variant carriers / Amandeep JUTLA in Autism Research, 13-2 (February 2020)  

Public ISBD [article]  inAutism Research > 13-2 (February 2020) . - p.187-198 Titre : Psychotic symptoms in 16p11.2 copy-number variant carriers Type de document : texte imprimé Auteurs : Amandeep JUTLA, Auteur ; J. Blake TURNER, Auteur ; LeeAnne GREEN SNYDER, Auteur ; Wendy K. CHUNG, Auteur ; Jeremy VEENSTRA-VANDERWEELE, Auteur Article en page(s) : p.187-198 Langues : Anglais (eng) Mots-clés : autism spectrum disorder  chromosome deletion  chromosome duplication  chromosomes  human  obsessive-compulsive disorder  pair 16  phenotype  schizophrenia spectrum and other psychotic disorders Index. décimale : PER Périodiques Résumé : 16p11.2 copy-number variation (CNV) is implicated in neurodevelopmental disorders, with the duplication and deletion associated with autism spectrum disorder (ASD) and the duplication associated with schizophrenia (SCZ). The 16p11.2 CNV may therefore provide insight into the relationship between ASD and SCZ, distinct disorders that co-occur at an elevated rate, and are difficult to distinguish from each other and from common co-occurring diagnoses such as obsessive compulsive disorder (OCD), itself a potential risk factor for SCZ. As psychotic symptoms are core to SCZ but distinct from ASD, we sought to examine their predictors in a population (n = 546) of 16p11.2 CNV carriers and their noncarrier siblings recruited by the Simons Variation in Individuals Project. We hypothesized that psychotic symptoms would be most common in duplication carriers followed by deletion carriers and noncarriers, that an ASD diagnosis would predict psychotic symptoms among CNV carriers, and that OCD symptoms would predict psychotic symptoms among all participants. Using data collected across multiple measures, we identified 19 participants with psychotic symptoms. Logistic regression models adjusting for biological sex, age, and IQ found that 16p11.2 duplication and ASD diagnosis predicted psychotic symptom presence. Our findings suggest that the association between 16p11.2 duplication and psychotic symptoms is independent of ASD diagnosis and that ASD diagnosis and psychotic symptoms may be associated in 16p11.2 CNV carriers. Autism Res 2020, 13: 187-198. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Either deletion or duplication at chromosome 16p11.2 raises the risk of autism spectrum disorder, and duplication, but not deletion, has been reported in schizophrenia (SCZ). In a sample of 16p11.2 deletion and duplication carriers, we found that having the duplication or having an autism diagnosis may increase the risk of psychosis, a key feature of SCZ. En ligne : http://dx.doi.org/10.1002/aur.2232 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=420 [article] Psychotic symptoms in 16p11.2 copy-number variant carriers [texte imprimé] / Amandeep JUTLA, Auteur ; J. Blake TURNER, Auteur ; LeeAnne GREEN SNYDER, Auteur ; Wendy K. CHUNG, Auteur ; Jeremy VEENSTRA-VANDERWEELE, Auteur . - p.187-198. Langues : Anglais (eng) in Autism Research > 13-2 (February 2020) . - p.187-198 Mots-clés : autism spectrum disorder  chromosome deletion  chromosome duplication  chromosomes  human  obsessive-compulsive disorder  pair 16  phenotype  schizophrenia spectrum and other psychotic disorders Index. décimale : PER Périodiques Résumé : 16p11.2 copy-number variation (CNV) is implicated in neurodevelopmental disorders, with the duplication and deletion associated with autism spectrum disorder (ASD) and the duplication associated with schizophrenia (SCZ). The 16p11.2 CNV may therefore provide insight into the relationship between ASD and SCZ, distinct disorders that co-occur at an elevated rate, and are difficult to distinguish from each other and from common co-occurring diagnoses such as obsessive compulsive disorder (OCD), itself a potential risk factor for SCZ. As psychotic symptoms are core to SCZ but distinct from ASD, we sought to examine their predictors in a population (n = 546) of 16p11.2 CNV carriers and their noncarrier siblings recruited by the Simons Variation in Individuals Project. We hypothesized that psychotic symptoms would be most common in duplication carriers followed by deletion carriers and noncarriers, that an ASD diagnosis would predict psychotic symptoms among CNV carriers, and that OCD symptoms would predict psychotic symptoms among all participants. Using data collected across multiple measures, we identified 19 participants with psychotic symptoms. Logistic regression models adjusting for biological sex, age, and IQ found that 16p11.2 duplication and ASD diagnosis predicted psychotic symptom presence. Our findings suggest that the association between 16p11.2 duplication and psychotic symptoms is independent of ASD diagnosis and that ASD diagnosis and psychotic symptoms may be associated in 16p11.2 CNV carriers. Autism Res 2020, 13: 187-198. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Either deletion or duplication at chromosome 16p11.2 raises the risk of autism spectrum disorder, and duplication, but not deletion, has been reported in schizophrenia (SCZ). In a sample of 16p11.2 deletion and duplication carriers, we found that having the duplication or having an autism diagnosis may increase the risk of psychosis, a key feature of SCZ. En ligne : http://dx.doi.org/10.1002/aur.2232 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=420

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