Delineating the psychiatric and behavioral phenotype of recurrent 2q13 deletions and duplications

Kate Wolfe; Andrew McQuillin; Viola Alesi; Elise Boudry Labis; Peter Cutajar; Bruno Dallapiccola; Maria Lisa Dentici; Anne Dieux-Coeslier; Benedicte Duban-Bedu; Tina Duelund Hjortshøj; Himanshu Goel; Sara Loddo; Deborah Morrogh; Anne-Laure Mosca-Boidron; Antonio Novelli; Laurence Olivier-Faivre; Jennifer Parker; Michael J Parker; Christine Patch; Anna L Pelling; Thomas Smol; Zeynep Tümer; Olivier Vanakker; Arie van Haeringen; Clémence Vanlerberghe; Andre Strydom; David Skuse; Nick Bass

doi:10.1002/ajmg.b.32627

Delineating the psychiatric and behavioral phenotype of recurrent 2q13 deletions and duplications

Kate Wolfe, Andrew McQuillin, Viola Alesi, Elise Boudry Labis, Peter Cutajar, Bruno Dallapiccola, Maria Lisa Dentici, Anne Dieux-Coeslier, Benedicte Duban-Bedu, Tina Duelund Hjortshøj, Himanshu Goel, Sara Loddo, Deborah Morrogh, Anne-Laure Mosca-Boidron, Antonio Novelli, Laurence Olivier-Faivre, Jennifer Parker, Michael J Parker, Christine Patch, Anna L PellingThomas Smol, Zeynep Tümer, Olivier Vanakker, Arie van Haeringen, Clémence Vanlerberghe, Andre Strydom, David Skuse, Nick Bass

Department of Clinical Medicine

4 Citations (Scopus)

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Abstract

Recurrent deletions and duplications at the 2q13 locus have been associated with developmental delay (DD) and dysmorphisms. We aimed to undertake detailed clinical characterization of individuals with 2q13 copy number variations (CNVs), with a focus on behavioral and psychiatric phenotypes. Participants were recruited via the Unique chromosomal disorder support group, U.K. National Health Service Regional Genetics Centres, and the DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources (DECIPHER) database. A review of published 2q13 patient case reports was undertaken to enable combined phenotypic analysis. We present a new case series of 2q13 CNV carriers (21 deletion, 4 duplication) and the largest ever combined analysis with data from published studies, making a total of 54 deletion and 23 duplication carriers. DD/intellectual disabilities was identified in the majority of carriers (79% deletion, 70% duplication), although in the new cases 52% had an IQ in the borderline or normal range. Despite the median age of the new cases being only 9 years, 64% had a clinical psychiatric diagnosis. Combined analysis found attention deficit hyperactivity disorder (ADHD) to be the most frequent diagnosis (48% deletion, 60% duplication), followed by autism spectrum disorders (33% deletion, 17% duplication). Aggressive (33%) and self-injurious behaviors (33%) were also identified in the new cases. CNVs at 2q13 are typically associated with DD with mildly impaired intelligence, and a high rate of childhood psychiatric diagnoses-particularly ADHD. We have further characterized the clinical phenotype related to imbalances of the 2q13 region and identified it as a region of interest for the neurobiological investigation of ADHD.

Original language	English
Journal	American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
Volume	177
Issue number	4
Pages (from-to)	397-405
Number of pages	9
ISSN	1552-4841
DOIs	https://doi.org/10.1002/ajmg.b.32627
Publication status	Published - Jun 2018

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Wolfe, K., McQuillin, A., Alesi, V., Boudry Labis, E., Cutajar, P., Dallapiccola, B., Dentici, M. L., Dieux-Coeslier, A., Duban-Bedu, B., Duelund Hjortshøj, T., Goel, H., Loddo, S., Morrogh, D., Mosca-Boidron, A.-L., Novelli, A., Olivier-Faivre, L., Parker, J., Parker, M. J., Patch, C., ... Bass, N. (2018). Delineating the psychiatric and behavioral phenotype of recurrent 2q13 deletions and duplications. American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, 177(4), 397-405. https://doi.org/10.1002/ajmg.b.32627

Wolfe, K, McQuillin, A, Alesi, V, Boudry Labis, E, Cutajar, P, Dallapiccola, B, Dentici, ML, Dieux-Coeslier, A, Duban-Bedu, B, Duelund Hjortshøj, T, Goel, H, Loddo, S, Morrogh, D, Mosca-Boidron, A-L, Novelli, A, Olivier-Faivre, L, Parker, J, Parker, MJ, Patch, C, Pelling, AL, Smol, T, Tümer, Z, Vanakker, O, van Haeringen, A, Vanlerberghe, C, Strydom, A, Skuse, D & Bass, N 2018, 'Delineating the psychiatric and behavioral phenotype of recurrent 2q13 deletions and duplications', American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, vol. 177, no. 4, pp. 397-405. https://doi.org/10.1002/ajmg.b.32627

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title = "Delineating the psychiatric and behavioral phenotype of recurrent 2q13 deletions and duplications",

abstract = "Recurrent deletions and duplications at the 2q13 locus have been associated with developmental delay (DD) and dysmorphisms. We aimed to undertake detailed clinical characterization of individuals with 2q13 copy number variations (CNVs), with a focus on behavioral and psychiatric phenotypes. Participants were recruited via the Unique chromosomal disorder support group, U.K. National Health Service Regional Genetics Centres, and the DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources (DECIPHER) database. A review of published 2q13 patient case reports was undertaken to enable combined phenotypic analysis. We present a new case series of 2q13 CNV carriers (21 deletion, 4 duplication) and the largest ever combined analysis with data from published studies, making a total of 54 deletion and 23 duplication carriers. DD/intellectual disabilities was identified in the majority of carriers (79% deletion, 70% duplication), although in the new cases 52% had an IQ in the borderline or normal range. Despite the median age of the new cases being only 9 years, 64% had a clinical psychiatric diagnosis. Combined analysis found attention deficit hyperactivity disorder (ADHD) to be the most frequent diagnosis (48% deletion, 60% duplication), followed by autism spectrum disorders (33% deletion, 17% duplication). Aggressive (33%) and self-injurious behaviors (33%) were also identified in the new cases. CNVs at 2q13 are typically associated with DD with mildly impaired intelligence, and a high rate of childhood psychiatric diagnoses-particularly ADHD. We have further characterized the clinical phenotype related to imbalances of the 2q13 region and identified it as a region of interest for the neurobiological investigation of ADHD.",

author = "Kate Wolfe and Andrew McQuillin and Viola Alesi and {Boudry Labis}, Elise and Peter Cutajar and Bruno Dallapiccola and Dentici, {Maria Lisa} and Anne Dieux-Coeslier and Benedicte Duban-Bedu and {Duelund Hjortsh{\o}j}, Tina and Himanshu Goel and Sara Loddo and Deborah Morrogh and Anne-Laure Mosca-Boidron and Antonio Novelli and Laurence Olivier-Faivre and Jennifer Parker and Parker, {Michael J} and Christine Patch and Pelling, {Anna L} and Thomas Smol and Zeynep T{\"u}mer and Olivier Vanakker and {van Haeringen}, Arie and Cl{\'e}mence Vanlerberghe and Andre Strydom and David Skuse and Nick Bass",

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T1 - Delineating the psychiatric and behavioral phenotype of recurrent 2q13 deletions and duplications

AU - Wolfe, Kate

AU - McQuillin, Andrew

AU - Alesi, Viola

AU - Boudry Labis, Elise

AU - Cutajar, Peter

AU - Dallapiccola, Bruno

AU - Dentici, Maria Lisa

AU - Dieux-Coeslier, Anne

AU - Duban-Bedu, Benedicte

AU - Duelund Hjortshøj, Tina

AU - Goel, Himanshu

AU - Loddo, Sara

AU - Morrogh, Deborah

AU - Mosca-Boidron, Anne-Laure

AU - Novelli, Antonio

AU - Olivier-Faivre, Laurence

AU - Parker, Jennifer

AU - Parker, Michael J

AU - Patch, Christine

AU - Pelling, Anna L

AU - Smol, Thomas

AU - Tümer, Zeynep

AU - Vanakker, Olivier

AU - van Haeringen, Arie

AU - Vanlerberghe, Clémence

AU - Strydom, Andre

AU - Skuse, David

AU - Bass, Nick

PY - 2018/6

Y1 - 2018/6

N2 - Recurrent deletions and duplications at the 2q13 locus have been associated with developmental delay (DD) and dysmorphisms. We aimed to undertake detailed clinical characterization of individuals with 2q13 copy number variations (CNVs), with a focus on behavioral and psychiatric phenotypes. Participants were recruited via the Unique chromosomal disorder support group, U.K. National Health Service Regional Genetics Centres, and the DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources (DECIPHER) database. A review of published 2q13 patient case reports was undertaken to enable combined phenotypic analysis. We present a new case series of 2q13 CNV carriers (21 deletion, 4 duplication) and the largest ever combined analysis with data from published studies, making a total of 54 deletion and 23 duplication carriers. DD/intellectual disabilities was identified in the majority of carriers (79% deletion, 70% duplication), although in the new cases 52% had an IQ in the borderline or normal range. Despite the median age of the new cases being only 9 years, 64% had a clinical psychiatric diagnosis. Combined analysis found attention deficit hyperactivity disorder (ADHD) to be the most frequent diagnosis (48% deletion, 60% duplication), followed by autism spectrum disorders (33% deletion, 17% duplication). Aggressive (33%) and self-injurious behaviors (33%) were also identified in the new cases. CNVs at 2q13 are typically associated with DD with mildly impaired intelligence, and a high rate of childhood psychiatric diagnoses-particularly ADHD. We have further characterized the clinical phenotype related to imbalances of the 2q13 region and identified it as a region of interest for the neurobiological investigation of ADHD.

AB - Recurrent deletions and duplications at the 2q13 locus have been associated with developmental delay (DD) and dysmorphisms. We aimed to undertake detailed clinical characterization of individuals with 2q13 copy number variations (CNVs), with a focus on behavioral and psychiatric phenotypes. Participants were recruited via the Unique chromosomal disorder support group, U.K. National Health Service Regional Genetics Centres, and the DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources (DECIPHER) database. A review of published 2q13 patient case reports was undertaken to enable combined phenotypic analysis. We present a new case series of 2q13 CNV carriers (21 deletion, 4 duplication) and the largest ever combined analysis with data from published studies, making a total of 54 deletion and 23 duplication carriers. DD/intellectual disabilities was identified in the majority of carriers (79% deletion, 70% duplication), although in the new cases 52% had an IQ in the borderline or normal range. Despite the median age of the new cases being only 9 years, 64% had a clinical psychiatric diagnosis. Combined analysis found attention deficit hyperactivity disorder (ADHD) to be the most frequent diagnosis (48% deletion, 60% duplication), followed by autism spectrum disorders (33% deletion, 17% duplication). Aggressive (33%) and self-injurious behaviors (33%) were also identified in the new cases. CNVs at 2q13 are typically associated with DD with mildly impaired intelligence, and a high rate of childhood psychiatric diagnoses-particularly ADHD. We have further characterized the clinical phenotype related to imbalances of the 2q13 region and identified it as a region of interest for the neurobiological investigation of ADHD.

U2 - 10.1002/ajmg.b.32627

DO - 10.1002/ajmg.b.32627

M3 - Journal article

C2 - 29603867

SN - 1552-4841

VL - 177

SP - 397

EP - 405

JO - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics

IS - 4

ER -

Delineating the psychiatric and behavioral phenotype of recurrent 2q13 deletions and duplications

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