{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:11:38Z","timestamp":1792141898173,"version":"4.4.0"},"reference-count":42,"publisher":"BMJ","issue":"6","funder":[{"DOI":"10.13039\/501100003246","name":"Dutch Research Council","doi-asserted-by":"crossref","award":["015.014.036"],"award-info":[{"award-number":["015.014.036"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003246","name":"Dutch Research Council","doi-asserted-by":"crossref","award":["1160.18.320"],"award-info":[{"award-number":["1160.18.320"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001826","name":"Netherlands Organisation for Health Research and Development","doi-asserted-by":"crossref","award":["10250022110003"],"award-info":[{"award-number":["10250022110003"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001826","name":"Netherlands Organisation for Health Research and Development","doi-asserted-by":"crossref","award":["91718310"],"award-info":[{"award-number":["91718310"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"crossref","award":["1105008"],"award-info":[{"award-number":["1105008"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"crossref","award":["1195955"],"award-info":[{"award-number":["1195955"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"crossref","award":["2015727"],"award-info":[{"award-number":["2015727"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"crossref","award":["2022156"],"award-info":[{"award-number":["2022156"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Victorian Government\u2019s Operational Infrastructure Support Program"},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["220100253"],"award-info":[{"award-number":["220100253"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institutes of Health\/National Institutes of Neurological Disorders and Stroke","award":["K23NS119666"],"award-info":[{"award-number":["K23NS119666"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2024,1,18]]},"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Speech and language impairments are core features of the neurodevelopmental genetic condition Kleefstra syndrome. Communication has not been systematically examined to guide intervention recommendations. We define the speech, language and cognitive phenotypic spectrum in a large cohort of individuals with Kleefstra syndrome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>103 individuals with Kleefstra syndrome (40 males, median age 9.5 years, range 1\u201343 years) with pathogenic variants (52 9q34.3 deletions, 50 intragenic variants, 1 balanced translocation) were included. Speech, language and non-verbal communication were assessed. Cognitive, health and neurodevelopmental data were obtained.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The cognitive spectrum ranged from average intelligence (12\/79, 15%) to severe intellectual disability (12\/79, 15%). Language ability also ranged from average (10\/90, 11%) to severely impaired (53\/90, 59%). Speech disorders occurred in 48\/49 (98%) verbal individuals and even occurred alongside average language and cognition. Developmental regression occurred in 11\/80 (14%) individuals across motor, language and psychosocial domains. Communication aids, such as sign and speech-generating devices, were crucial for 61\/103 (59%) individuals including those who were minimally verbal, had a speech disorder or following regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The speech, language and cognitive profile of Kleefstra syndrome is broad, ranging from severe impairment to average ability. Genotype and age do not explain the phenotypic variability. Early access to communication aids may improve communication and quality of life.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jmg-2023-109702","type":"journal-article","created":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T13:20:56Z","timestamp":1706620856000},"page":"578-585","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":21,"title":["Expanding the phenotype of Kleefstra syndrome: speech, language and cognition in 103 individuals"],"prefix":"10.1136","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2822-6522","authenticated-orcid":false,"given":"Lottie D.","family":"Morison","sequence":"first","affiliation":[{"name":"Speech and Language, Murdoch Children's Research Institute, Parkville, Victoria, Australia"},{"name":"Department of Audiology and Speech Pathology, The University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milou G.P.","family":"Kennis","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Radboudumc, Nijmegen, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitrijs","family":"Rots","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus MC, Rotterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianne","family":"Bouman","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Radboudumc, Nijmegen, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost","family":"Kummeling","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Radboudumc, Nijmegen, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Palmer","sequence":"additional","affiliation":[{"name":"Sydney Children\u2019s Hospital Network, Randwick, New South Wales, Australia"},{"name":"Discipline of Paediatrics and Child Health, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3505-2631","authenticated-orcid":false,"given":"Adam P.","family":"Vogel","sequence":"additional","affiliation":[{"name":"Department of Audiology and Speech Pathology, The University of Melbourne, Melbourne, Victoria, Australia"},{"name":"Redenlab, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederique","family":"Liegeois","sequence":"additional","affiliation":[{"name":"Great Ormond Street Institute of Child Health, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Brignell","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Monash University, Clayton, Victoria, Australia"},{"name":"Department of Developmental Paediatrics, Monash Children\u2019s Hospital, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7008-1879","authenticated-orcid":false,"given":"Siddharth","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children\u2019s Hospital, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe","family":"Frazier","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children\u2019s Hospital, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Milnes","sequence":"additional","affiliation":[{"name":"Genetic Health Queensland, Herston, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Himanshu","family":"Goel","sequence":"additional","affiliation":[{"name":"Hunter Genetics, Waratah, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Amor","sequence":"additional","affiliation":[{"name":"Speech and Language, Murdoch Children's Research Institute, Parkville, Victoria, Australia"},{"name":"Department of Paediatrics, Royal Children's Hospital, Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid E.","family":"Scheffer","sequence":"additional","affiliation":[{"name":"Melbourne Brain Centre, Austin Health, Heidelberg, Victoria, Australia"},{"name":"The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tjitske","family":"Kleefstra","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Radboudumc, Nijmegen, Netherlands"},{"name":"Department of Clinical Genetics, Erasmus MC, Rotterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1147-7405","authenticated-orcid":false,"given":"Angela T.","family":"Morgan","sequence":"additional","affiliation":[{"name":"Speech and Language, Murdoch Children's Research Institute, Parkville, Victoria, Australia"},{"name":"Department of Audiology and Speech Pathology, The University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2024,1,30]]},"reference":[{"key":"2025101723222089000_61.6.578.1","doi-asserted-by":"crossref","DOI":"10.1186\/s13229-018-0193-9","article-title":"EHMT1 mosaicism in apparently unaffected parents is associated with autism spectrum disorder and neurocognitive dysfunction","volume":"9","author":"de Boer","year":"2018","journal-title":"Mol Autism"},{"key":"2025101723222089000_61.6.578.2","unstructured":"Kleefstra T , de Leeuw N . Kleefstra syndrome. In: GeneReviews\u00ae[Internet]. 2023."},{"key":"2025101723222089000_61.6.578.3","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37575"},{"key":"2025101723222089000_61.6.578.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2016.09.031"},{"key":"2025101723222089000_61.6.578.5","doi-asserted-by":"publisher","DOI":"10.1097\/WNF.0000000000000226"},{"key":"2025101723222089000_61.6.578.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2023.105293"},{"key":"2025101723222089000_61.6.578.7","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-021-00894-x"},{"key":"2025101723222089000_61.6.578.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-022-01079-w"},{"key":"2025101723222089000_61.6.578.9","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.14955"},{"key":"2025101723222089000_61.6.578.10","doi-asserted-by":"publisher","DOI":"10.1136\/jmg-2022-108734"},{"key":"2025101723222089000_61.6.578.11","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62899"},{"key":"2025101723222089000_61.6.578.12","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-022-01230-7"},{"key":"2025101723222089000_61.6.578.13","doi-asserted-by":"publisher","DOI":"10.1111\/apa.14299"},{"key":"2025101723222089000_61.6.578.14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2010.03646.x"},{"key":"2025101723222089000_61.6.578.15","unstructured":"Sparrow S , Cicchetti D , Saulnier C . Vineland adaptive behavior scales\u2013third edition (Vineland-3). Pearson, 2016."},{"key":"2025101723222089000_61.6.578.16","doi-asserted-by":"crossref","unstructured":"Sparrow SS , Cicchetti D . Vineland adaptive behavior scales\u2013second edition (Vineland-2). Pearson, 2005.","DOI":"10.1037\/t15164-000"},{"key":"2025101723222089000_61.6.578.17","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-020-00885-2"},{"key":"2025101723222089000_61.6.578.18","unstructured":"Bishop DV . Children\u2019s Communication Checklist-second edition (CCC-2). London: Harcourt Assessment, 2003."},{"key":"2025101723222089000_61.6.578.19","unstructured":"Constantino JN , Gruber CP . Social responsiveness scale: SRS-2. Pearson, 2012."},{"key":"2025101723222089000_61.6.578.20","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association . Diagnostic and statistical manual of mental disorders. 2022. doi:10.1176\/appi.books.9780890425787","DOI":"10.1176\/appi.books.9780890425787"},{"key":"2025101723222089000_61.6.578.21","unstructured":"Rowland C . Communication matrix. Oregon Health & Science University, 2004."},{"key":"2025101723222089000_61.6.578.22","unstructured":"Dodd B , Zhu H , Crosbie S , et al . Diagnostic evaluation of articulation and phonology (DEAP). Psychology Corporation, 2002."},{"key":"2025101723222089000_61.6.578.23","unstructured":"American Speech Language and Hearing Association . Childhood Apraxia of speech technical report. 2007. Available: https:\/\/www.asha.org\/policy\/tr2007-00278\/"},{"key":"2025101723222089000_61.6.578.24","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-018-0102-x"},{"key":"2025101723222089000_61.6.578.25","unstructured":"Duffy JR . Motor Speech disorders-E-Book: Substrates, differential diagnosis, and management. Elsevier Health Sciences, 2012."},{"key":"2025101723222089000_61.6.578.26","unstructured":"Onslow M , Webber M , Harrison E , et al . The Lidcombe program treatment guide. Lidcombe Program Trainers Consortium 2020."},{"key":"2025101723222089000_61.6.578.27","doi-asserted-by":"publisher","DOI":"10.1044\/2015_LSHSS-14-0120"},{"key":"2025101723222089000_61.6.578.28","doi-asserted-by":"crossref","first-page":"e194","DOI":"10.1212\/WNL.0000000000009776","article-title":"Features of speech and swallowing dysfunction in pre-ataxic spinocerebellar ataxia type 2","volume":"95","author":"Vogel","year":"2020","journal-title":"Neurology"},{"key":"2025101723222089000_61.6.578.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2016.01.004"},{"key":"2025101723222089000_61.6.578.30","doi-asserted-by":"publisher","DOI":"10.1080\/02699206.2019.1595731"},{"key":"2025101723222089000_61.6.578.31","doi-asserted-by":"publisher","DOI":"10.1080\/17518423.2023.2218485"},{"key":"2025101723222089000_61.6.578.32","article-title":"Interventions for childhood apraxia of speech","volume":"5","author":"Morgan","year":"2018","journal-title":"Cochrane Database Syst Rev"},{"key":"2025101723222089000_61.6.578.33","article-title":"Speech therapy for children with dysarthria acquired before three years of age","volume":"7","author":"Pennington","year":"2016","journal-title":"Cochrane Database Syst Rev"},{"key":"2025101723222089000_61.6.578.34","doi-asserted-by":"publisher","DOI":"10.1080\/07434618.2018.1461240"},{"key":"2025101723222089000_61.6.578.35","doi-asserted-by":"publisher","DOI":"10.1007\/s10882-021-09790-0"},{"key":"2025101723222089000_61.6.578.36","doi-asserted-by":"publisher","DOI":"10.1097\/00001163-200507000-00002"},{"key":"2025101723222089000_61.6.578.37","doi-asserted-by":"crossref","DOI":"10.1186\/s12966-020-00976-x","article-title":"Combinations of physical activity, sedentary time, and sleep duration and their associations with depressive symptoms and other mental health problems in children and adolescents: a systematic review","volume":"17","author":"Sampasa-Kanyinga","year":"2020","journal-title":"Int J Behav Nutr Phys Act"},{"key":"2025101723222089000_61.6.578.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2017.01.054"},{"key":"2025101723222089000_61.6.578.39","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34186"},{"key":"2025101723222089000_61.6.578.40","doi-asserted-by":"crossref","unstructured":"Havdahl A , Farmer C , Sur\u00e9n P , et al . Attainment and loss of early social-communication skills across neurodevelopmental conditions in the Norwegian Mother, Father and Child Cohort Study. J Child Psychol Psychiatry 2023. doi:10.1111\/jcpp.13792 [Epub ahead of print 27 Mar 2023].","DOI":"10.1111\/jcpp.13792"},{"key":"2025101723222089000_61.6.578.41","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-019-12947-3","article-title":"Neuronal network dysfunction in a model for Kleefstra syndrome mediated by enhanced NMDAR signaling","volume":"10","author":"Frega","year":"2019","journal-title":"Nat Commun"},{"key":"2025101723222089000_61.6.578.42","doi-asserted-by":"crossref","DOI":"10.1016\/j.isci.2021.102741","article-title":"Derepression of inflammation-related genes link to microglia activation and neural maturation defect in a mouse model of Kleefstra syndrome","volume":"24","author":"Yamada","year":"2021","journal-title":"iScience"}],"updated-by":[{"DOI":"10.1136\/jmg-2023-109702.corr1","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000}}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg-2023-109702","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T06:22:32Z","timestamp":1760768552000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg-2023-109702"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,30]]},"references-count":42,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,5,21]]},"published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1136\/jmg-2023-109702"],"URL":"https:\/\/doi.org\/10.1136\/jmg-2023-109702","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,30]]}}}