Browsing by Author "van den Bree, Marianne B.M. (57204543263)"

Objective: Certain copy number variants (CNVs) greatly increase the risk of autism. The authors conducted a genetics-first study to investigate whether heterogeneity in the clinical presentation of autism is underpinned by specific genotype-phenotype relationships. Methods: This international study included 547 individuals (mean age, 12.3 years [SD=4.2], 54% male) who were ascertained on the basis of having a genetic diagnosis of a rare CNV associated with high risk of autism (82 16p11.2 deletion carriers, 50 16p11.2 duplication carriers, 370 22q11.2 deletion carriers, and 45 22q11.2 duplication carriers), as well as 2,027 individuals (mean age, 9.1 years [SD=4.9], 86% male) with autism of heterogeneous etiology. Assessments included the Autism Diagnostic Interview-Revised and IQ testing. Results: The four genetic variant groups differed in autism symptom severity, autism subdomain profile, and IQ profile. However, substantial variability was observed in phenotypic outcome in individual genetic variant groups (74%-97% of the variance, depending on the trait), whereas variability between groups was low (1%-21%, depending on the trait). CNV carriers who met autism criteria were compared with individuals with heterogeneous autism, and a range of profile differences were identified. When clinical cutoff scores were applied, 54% of individuals with one of the four CNVs who did not meet full autism diagnostic criteria had elevated levels of autistic traits. Conclusions: Many CNV carriers do not meet full diagnostic criteria for autism but nevertheless meet clinical cutoffs for autistic traits. Although profile differences between variants were observed, there is considerable variability in clinical symptoms in the same variant. © 2021 American Psychiatric Association. All rights reserved.

Background: Several rare copy number variants have been identified to confer risk for neurodevelopmental disorders (NDD-CNVs), and increasingly NDD-CNVs are being identified in patients. There is a clinical need to understand the phenotypes of NDD-CNVs. However due to rarity of NDD-CNVs in the population, within individual countries there is a limited number of NDD-CNV carriers who can participate in research. The pan-european MINDDS (Maximizing Impact of Research in Neurodevelopmental Disorders) consortium was established in part to address this issue. Methodology: A survey was developed to scope out the current landscape of NDD-CNV research across member countries of the MINDDS consortium, and to identify clinical cohorts with potential for future research. Results: 36 centres from across 16 countries completed the survey. We provide a list of centres who can be contacted for future collaborations. 3844 NDD-CNV carriers were identified across clinical and research centres spanning a range of medical specialties, including psychiatry, paediatrics, medical genetics. A broad range of phenotypic data was available; including medical history, developmental history, family history and anthropometric data. In 12/16 countries, over 75% of NDD-CNV carriers could be recontacted for future studies. Conclusion: This survey has highlighted the potential within Europe for large multi-centre studies of NDD-CNV carriers, to improve knowledge of the complex relationship between NDD-CNV and clinical phenotype. The MINNDS consortium is in a position to facilitate collaboration, data-sharing and knowledge exchange on NDD-CNV phenotypes across Europe. © 2020 The Authors

Background: Several rare copy number variants have been identified to confer risk for neurodevelopmental disorders (NDD-CNVs), and increasingly NDD-CNVs are being identified in patients. There is a clinical need to understand the phenotypes of NDD-CNVs. However due to rarity of NDD-CNVs in the population, within individual countries there is a limited number of NDD-CNV carriers who can participate in research. The pan-european MINDDS (Maximizing Impact of Research in Neurodevelopmental Disorders) consortium was established in part to address this issue. Methodology: A survey was developed to scope out the current landscape of NDD-CNV research across member countries of the MINDDS consortium, and to identify clinical cohorts with potential for future research. Results: 36 centres from across 16 countries completed the survey. We provide a list of centres who can be contacted for future collaborations. 3844 NDD-CNV carriers were identified across clinical and research centres spanning a range of medical specialties, including psychiatry, paediatrics, medical genetics. A broad range of phenotypic data was available; including medical history, developmental history, family history and anthropometric data. In 12/16 countries, over 75% of NDD-CNV carriers could be recontacted for future studies. Conclusion: This survey has highlighted the potential within Europe for large multi-centre studies of NDD-CNV carriers, to improve knowledge of the complex relationship between NDD-CNV and clinical phenotype. The MINNDS consortium is in a position to facilitate collaboration, data-sharing and knowledge exchange on NDD-CNV phenotypes across Europe. © 2020 The Authors