{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T04:41:57Z","timestamp":1793248917716,"version":"4.5.0"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,9,19]],"date-time":"2019-09-19T00:00:00Z","timestamp":1568851200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000073","name":"Autism Speaks","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000073","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000311","name":"Tuberous Sclerosis Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000311","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001262","name":"Baily Thomas Charitable Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001262","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G9817803"],"award-info":[{"award-number":["G9817803"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Develop Med Child Neuro"],"published-print":{"date-parts":[[2020,3]]},"abstract":"\n Aim<\/jats:title>\n \n To investigate the interdependence between risk factors associated with long\u2010term intellectual development in individuals with tuberous sclerosis complex (\n TSC<\/jats:styled-content>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Method<\/jats:title>\n \n The Tuberous Sclerosis 2000 Study is a prospective longitudinal study of individuals with\n TSC<\/jats:styled-content>\n . In phase 1 of the study, baseline measures of intellectual ability, epilepsy, cortical tuber load, and mutation were obtained for 125 children (63 females, 62 males; median age=39mo). In phase 2, at an average of 8 years later, intellectual abilities were estimated for 88 participants with\n TSC<\/jats:styled-content>\n and 35 unaffected siblings. Structural equation modelling was used to determine the risk pathways from genetic mutation through to\n IQ<\/jats:styled-content>\n at phase 2.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Intellectual disability was present in 57% of individuals with\n TSC<\/jats:styled-content>\n . Individuals without intellectual disability had significantly lower mean\n IQ<\/jats:styled-content>\n compared to unaffected siblings, supporting specific genetic factors associated with intellectual impairment. Individuals with\n TSC<\/jats:styled-content>\n who had a slower gain in\n IQ<\/jats:styled-content>\n from infancy to middle childhood were younger at seizure onset and had increased infant seizure severity. Structural equation modelling indicated indirect pathways from genetic mutation, to tuber count, to seizure severity in infancy, through to\n IQ<\/jats:styled-content>\n in middle childhood and adolescence.\n <\/jats:p>\n <\/jats:sec>\n \n Interpretation<\/jats:title>\n \n Early\u2010onset and severe epilepsy in the first 2\u00a0years of life are associated with increased risk of long\u2010term intellectual disability in individuals with\n TSC<\/jats:styled-content>\n , emphasizing the importance of early and effective treatment or prevention of epilepsy.\n <\/jats:p>\n <\/jats:sec>\n \n What this paper adds<\/jats:title>\n \n \n \n Intellectual disability was present in 57% of individuals with tuberous sclerosis complex (TSC).<\/jats:p>\n <\/jats:list-item>\n \n Those with TSC\u00a0without intellectual disability had significantly lower mean IQ compared to unaffected siblings.<\/jats:p>\n <\/jats:list-item>\n \n Earlier onset and greater severity of seizures in the first 2\u00a0years were observed in individuals with a slower gain in intellectual ability.<\/jats:p>\n <\/jats:list-item>\n \n Risk pathways\u00a0through seizures in the first 2 years predict long\u2010term cognitive outcomes in individuals with TSC.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/dmcn.14356","type":"journal-article","created":{"date-parts":[[2019,9,20]],"date-time":"2019-09-20T01:49:52Z","timestamp":1568944192000},"page":"322-329","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Long\u2010term cognitive outcomes in tuberous sclerosis complex"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8567-9547","authenticated-orcid":false,"given":"Charlotte","family":"Tye","sequence":"first","affiliation":[{"name":"Department of Child & Adolescent Psychiatry Institute of Psychiatry, Psychology & Neuroscience King's College London London UK"},{"name":"Social Genetic & Developmental Psychiatry Centre Institute of Psychiatry, Psychology & Neuroscience King's College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona S","family":"Mcewen","sequence":"additional","affiliation":[{"name":"Department of Child & Adolescent Psychiatry Institute of Psychiatry, Psychology & Neuroscience King's College London London UK"},{"name":"Social Genetic & Developmental Psychiatry Centre Institute of Psychiatry, Psychology & Neuroscience King's College London London UK"},{"name":"Department of Biological and Experimental Psychology School of Biological and Chemical Sciences Queen Mary University of London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holan","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Child & Adolescent Psychiatry Institute of Psychiatry, Psychology & Neuroscience King's College London London UK"},{"name":"Great Ormond Street Hospital NHS Trust London UK"},{"name":"Institute of Child Health University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Underwood","sequence":"additional","affiliation":[{"name":"Department of Population Health University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Woodhouse","sequence":"additional","affiliation":[{"name":"Forensic and Neurodevelopmental Sciences Institute of Psychiatry, Psychology & Neuroscience King's College London London UK"},{"name":"South London and Maudsley NHS Trust London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward D","family":"Barker","sequence":"additional","affiliation":[{"name":"Department of Psychology Institute of Psychiatry, Psychology & Neuroscience King's College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fintan","family":"Sheerin","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology Oxford University Hospital NHS Foundation Trust Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R W","family":"Yates","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Cambridge University Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick F","family":"Bolton","sequence":"additional","affiliation":[{"name":"Department of Child & Adolescent Psychiatry Institute of Psychiatry, Psychology & Neuroscience King's College London London UK"},{"name":"Social Genetic & Developmental Psychiatry Centre Institute of Psychiatry, Psychology & Neuroscience King's College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Tuberous Sclerosis 2000 Study 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