{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:05:48Z","timestamp":1790949948197,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T00:00:00Z","timestamp":1635465600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Tuberous sclerosis complex (TSC) is highly associated with autism spectrum disorder (ASD). Objectives of the study were to characterize autistic features in young children with TSC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Participants included 138 children followed from ages 3 to 36\u2009months with TSC from the Tuberous Sclerosis Complex Autism Center of Excellence Research Network (TACERN), a multicenter, prospective observational study aimed at understanding the underlying mechanisms of ASD in TSC. Developmental and autism\u2010specific assessments were administered, and a clinical diagnosis of ASD was determined for all participants at 36\u2009months. Further analyses were performed on 117 participants with valid autism assessments based on nonverbal mental age greater than 15\u2009months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Prevalence of clinical diagnosis of ASD at 36\u2009months was 25%. Nearly all autistic behaviors on the Autism Diagnostic Observation Schedule\u20102 (ADOS\u20102) and Autism Diagnostic Interview\u2010Revised (ADI\u2010R) were more prevalent in children diagnosed with ASD; however, autism\u2010specific behaviors were also observed in children without ASD. Overall quality of social overtures, facial expressions, and abnormal repetitive interests and behaviors were characteristics most likely to distinguish children with ASD from those without an ASD diagnosis. Participants meeting ADOS\u20102 criteria but not a clinical ASD diagnosis exhibited intermediate developmental and ADOS\u20102 scores compared to individuals with and without ASD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>ASD is highly prevalent in TSC, and many additional individuals with TSC exhibit a broad range of subthreshold autistic behaviors. Our findings reveal a broader autism phenotype that can be identified in young children with TSC, which provides opportunity for early targeted treatments. 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Lurie Children's Hospital of Chicago Northwestern University Feinberg School of Medicine  Chicago IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7044-2953","authenticated-orcid":false,"given":"Mustafa","family":"Sahin","sequence":"additional","affiliation":[{"name":"Department of Neurology Rosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital  Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7250-7391","authenticated-orcid":false,"given":"Darcy A.","family":"Krueger","sequence":"additional","affiliation":[{"name":"Department of Neurology Cincinnati Children's Hospital Medical Center  Cincinnati OH"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"TACERN Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,29]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)00069-1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00787-005-0443-1"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00787-006-0570-3"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2014.10.004"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2013.08.002"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2004.08.005"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2007.07.010"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1026004501631"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073807309788"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.ss6904a1"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10803-004-1038-2"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfma.2014.02.008"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000568"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182104347"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/08830738060210020901"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-018-0901-8"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2013.08.001"},{"key":"e_1_2_9_19_1","volume-title":"Mullen scales of early learning","author":"Mullen E","year":"1995"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003002"},{"key":"e_1_2_9_21_1","volume-title":"Vineland adaptive behavior scales second edition survey forms manual","author":"Sparrow SS","year":"2005"},{"key":"e_1_2_9_22_1","volume-title":"Preschool language scale, fifth edition (PLS\u20105)","author":"Zimmerman I","year":"2011"},{"key":"e_1_2_9_23_1","volume-title":"An integrated system of multi\u2010informant assessment; child behavior checklist for ages 1 1\/2\u20135; language development survey. 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