{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:36:59Z","timestamp":1790019419372,"version":"4.0.1"},"reference-count":90,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2018,9,8]],"date-time":"2018-09-08T00:00:00Z","timestamp":1536364800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["5U01MH101722\u201002"],"award-info":[{"award-number":["5U01MH101722\u201002"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:p>The purpose of this article is to provide an overview of current insights into the neurodevelopmental and psychiatric manifestations of 22q11.2 deletion syndrome (22q11DS) in children and adolescents. The pediatric neuropsychiatric expression of 22q11DS is characterized by high variability, both interindividual and intraindividual (different expressions over the lifespan). Besides varying levels of intellectual disability, the prevalence of autism spectrum disorders, attention deficit disorders, anxiety disorders, and psychotic disorders in young individuals with 22q11DS is significantly higher than in the general population, or in individuals with idiopathic intellectual disability. Possible explanations for this observed phenotypic variability will be discussed, including genetic pleiotropy, gene\u2010environment interactions, the age\u2010dependency of phenotypes, but also the impact of assessment and ascertainment bias as well as the limitations of our current diagnostic classification system. The implications inferred by these observations aforementioned bear direct relevance to both scientists and clinicians. Observations regarding the neuropsychiatric manifestations in individuals with 22q11DS exemplify the need for a <jats:italic>dimensional approach<\/jats:italic> to neuropsychiatric assessment, in addition to our current categorical diagnostic classification system. The potential usefulness of 22q11DS as a <jats:italic>genetic model<\/jats:italic> to study the early phases of schizophrenia as well as the phenomenon of neuropsychiatric pleiotropy observed in many CNV's will be delineated. From a clinical perspective, the importance of <jats:italic>regular neuropsychiatric evaluations<\/jats:italic> with attention to <jats:italic>symptoms<\/jats:italic> not always captured in diagnostic categories and of <jats:italic>maintaining equilibrium<\/jats:italic> between individual difficulties and competencies and environmental demands will be discussed.<\/jats:p>","DOI":"10.1002\/ajmg.a.40387","type":"journal-article","created":{"date-parts":[[2018,9,8]],"date-time":"2018-09-08T15:54:41Z","timestamp":1536422081000},"page":"2182-2191","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Understanding the pediatric psychiatric phenotype of 22q11.2 deletion syndrome"],"prefix":"10.1002","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8169-7721","authenticated-orcid":false,"given":"Ania M.","family":"Fiksinski","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Rudolf Magnus Institute of Neuroscience University Medical Center Utrecht  Utrecht The Netherlands"},{"name":"Dalglish Family 22q Clinic for Adults with 22q11.2 Deletion Syndrome Toronto General Hospital, University Health Network, and Clinical Genetics Research Program, Centre for Addiction and Mental Health  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maude","family":"Schneider","sequence":"additional","affiliation":[{"name":"Developmental Imaging and Psychopathology Lab, Department of Psychiatry, School of Medicine University of Geneva  Geneva Switzerland"},{"name":"Center for Contextual Psychiatry, Department of Neurosciences KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clodagh M.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Sackler Institute for Translational Neurodevelopment and Department of Forensic and Neurodevelopmental Sciences, King's College London Institute of Psychiatry, Psychology &amp; Neuroscience  London UK"},{"name":"Behavioural and Developmental Psychiatry Clinical Academic Group Behavioural Genetics Clinic, Adult Autism and ADHD Service, South London and Maudsley Foundation NHS Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Armando","sequence":"additional","affiliation":[{"name":"Developmental Imaging and Psychopathology Lab, Department of Psychiatry, School of Medicine University of Geneva  Geneva Switzerland"},{"name":"Child and Adolescence Neuropsychiatry Unit, Department of Neuroscience Children Hospital Bambino Ges\u00f9  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Vicari","sequence":"additional","affiliation":[{"name":"Child and Adolescence Neuropsychiatry Unit, Department of Neuroscience Children Hospital Bambino Ges\u00f9  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaume M.","family":"Canyelles","sequence":"additional","affiliation":[{"name":"Hospital Universitario Fundacion Alcorcon  Alcorcon Espana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doron","family":"Gothelf","sequence":"additional","affiliation":[{"name":"Child and Adolescent Psychiatry Unit Edmond and Lily Safra Children's Hospital, Sheba Medical Center Sagol School of Neuroscience and Sackler School of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Eliez","sequence":"additional","affiliation":[{"name":"Developmental Imaging and Psychopathology Lab, Department of Psychiatry, School of Medicine University of Geneva  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elemi J.","family":"Breetvelt","sequence":"additional","affiliation":[{"name":"Dalglish Family 22q Clinic for Adults with 22q11.2 Deletion Syndrome Toronto General Hospital, University Health Network, and Clinical Genetics Research Program, Centre for Addiction and Mental Health  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celso","family":"Arango","sequence":"additional","affiliation":[{"name":"Child and Adolescent Psychiatry Department Hospital General Universitario Gregorio Mara\u00f1\u00f3n, IiSGM, School of Medicine, Universidad Complutense, CIBERSAM  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob A. S.","family":"Vorstman","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Rudolf Magnus Institute of Neuroscience University Medical Center Utrecht  Utrecht The Netherlands"},{"name":"Department of Psychiatry The Hospital for Sick Children and University of Toronto  Toronto Ontario Canada"},{"name":"Program in Genetics and Genome Biology, Research Institute, The Hospital for Sick Children  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/jir.12054"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1542\/peds.110.S3.1304","article-title":"A consensus statement on health care transitions for young adults with special health care needs","volume":"110","author":"American Academy of Pediatrics; American Academy of Family Physicians; American College of Physicians\u2010American Society of Internal Medicine","year":"2002","journal-title":"Pediatrics"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.chi.0000205703.25453.5a"},{"issue":"4","key":"e_1_2_8_5_1","first-page":"333","article-title":"Cognitive and psychiatric predictors to psychosis in velocardiofacial syndrome: A 3\u2010year follow\u2010up study","volume":"49","author":"Antshel K. M.","year":"2010","journal-title":"Journal of the American Academy of Child and Adolescent Psychiatry"},{"issue":"10","key":"e_1_2_8_6_1","first-page":"1","article-title":"Prevalence of autism spectrum disorders \u2010 Autism and Developmental Disabilities Monitoring Network, United States, 2006","volume":"58","author":"Autism and Developmental Disabilities Monitoring Network Surveillance Year 2006 Principal Investigators; Centers for Disease Control and Prevention (CDC)","year":"2009","journal-title":"MMWR. Surveillance Summaries"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e328352dd58"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291716000970"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1037\/10422-000"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2006.07.038"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11920-008-0026-1"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.160.9.1580"},{"issue":"4","key":"e_1_2_8_13_1","first-page":"307","article-title":"Clinical features of 78 adults with 22q11 Deletion Syndrome. American Journal of Medical Genetics","volume":"138","author":"Bassett A. S.","year":"2005","journal-title":"Part A"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19980710)81:4<328::AID-AJMG10>3.0.CO;2-N"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2011.02.039"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2009.09071016"},{"issue":"10","key":"e_1_2_8_17_1","first-page":"2350","article-title":"Disclosure of psychiatric manifestations of 22q11.2 deletion syndrome in medical genetics: A 12\u2010year retrospective chart review. American Journal of Medical Genetics","volume":"167","author":"Baughman S. T.","year":"2015","journal-title":"Part A"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11689-010-9069-9"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/1355819614527439"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/2040-2392-5-11"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004583-198705000-00012"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ridd.2012.02.009"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2006.04.007"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaac.2013.09.017"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.60.8.837"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2788.2007.00955.x"},{"issue":"2","key":"e_1_2_8_27_1","first-page":"1","article-title":"Prevalence of autism spectrum disorder among children aged 8 years \u2010 autism and developmental disabilities monitoring network, 11 sites, United States, 2010","volume":"63","author":"Developmental Disabilities Monitoring Network Surveillance Year 2010 Principal Investigators; Centers for Disease Control and Prevention (CDC)","year":"2014","journal-title":"MMWR. Surveillance Summaries"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.111.097139"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1080\/13668250.2011.572548"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.107.038729"},{"issue":"4","key":"e_1_2_8_31_1","first-page":"307","article-title":"The velo\u2010cardio\u2010facial syndrome: The spectrum of psychiatric problems and cognitive deterioration at adult age","volume":"20","author":"Evers L. J.","year":"2009","journal-title":"Genetic Counseling (Geneva, Switzerland)"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/jir.12117"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpp.12037"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2017.01.032"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.175"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2013.269"},{"key":"e_1_2_8_37_1","volume-title":"Epidemiology of early onset schizophrenia","author":"Gillberg C.","year":"2001"},{"issue":"4","key":"e_1_2_8_38_1","first-page":"999","article-title":"Novel features of 3q29 deletion syndrome: Results from the 3q29 registry. American Journal of Medical Genetics","volume":"170","author":"Glassford M. R.","year":"2016","journal-title":"Part A"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaac.2013.08.008"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2017.161"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds180"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004583-198705000-00013"},{"issue":"18","key":"e_1_2_8_43_1","first-page":"2355","article-title":"Living with a child at risk for psychotic illness: The experience of parents coping with 22q11 deletion syndrome: An exploratory study. American Journal of Medical Genetics","volume":"146","author":"Hercher L.","year":"2008","journal-title":"Part A"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2016.3939"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09552"},{"issue":"6","key":"e_1_2_8_46_1","first-page":"574","article-title":"Behavioral problems in relation to intelligence in children with 22q11.2 deletion syndrome: A matched control study. American Journal of Medical Genetics","volume":"143","author":"Jansen P. W.","year":"2007","journal-title":"Part A"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2009.02.016"},{"key":"e_1_2_8_48_1","volume-title":"State estimates of major depressive episode among adolescents: 2013 and 2014","author":"Lipari R. N.","year":"2013"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.02.039"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2015.71"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/epirev\/mxn001"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2014.2147"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2013.31"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S65455"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.56.10.940"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2017.0001"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.113.132324"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ridd.2008.10.007"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)01121-6"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.23512"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1177\/1359104514526603"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.2007.164.6.942"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005053-199408000-00010"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2016.11.041"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl443"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-016-1548-z"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/wps.20347"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2013.13070864"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2013.10.010"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10897-010-9309-x"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2006.00569.x"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320420131"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1352\/1944-7558-117.1.1"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/npjschz.2016.3"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2009.03419.x"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ridd.2016.03.019"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1097\/YCO.0000000000000231"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1076\/0929-7049(199912)05:04;1-R;FT230"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291713001669"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2014.05.036"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1097\/YCO.0000000000000324"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2014.2671"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2012.10.010"},{"key":"e_1_2_8_84_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.chi.0000228131.56956.c1"},{"key":"e_1_2_8_85_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e32835f1a30"},{"key":"e_1_2_8_86_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2017.4"},{"key":"e_1_2_8_87_1","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbx005"},{"key":"e_1_2_8_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rasd.2011.06.008"},{"key":"e_1_2_8_89_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-244X-11-174"},{"key":"e_1_2_8_90_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4524"},{"key":"e_1_2_8_91_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4000575"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.40387","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.40387","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T19:15:21Z","timestamp":1694459721000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.40387"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,8]]},"references-count":90,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2018,10]]}},"alternative-id":["10.1002\/ajmg.a.40387"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.40387","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,8]]},"assertion":[{"value":"2017-10-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}