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Two\u2010hundred and seventy two evaluations were collected from 148 prenatally diagnosed boys with 47,XXY between 0 and 36\u2009months and separated into one of three groups, depending on visit age: Y1 (0\u201312\u2009months; <jats:italic>n<\/jats:italic> = 100), Y2 (13\u201324\u2009months; <jats:italic>n<\/jats:italic> = 90), and Y3 (25\u201336\u2009months; <jats:italic>n<\/jats:italic> = 82). Those who received EHT (administered by 12\u2009months) were further separated (Y1, <jats:italic>n<\/jats:italic> = 37; Y2, <jats:italic>n<\/jats:italic> = 34; Y3, <jats:italic>n<\/jats:italic> = 30). Neurodevelopmental evaluations consisted of Preschool Language Scales, Early Language Milestone Scale, and Bayley Scales of Infant and Toddler Development and evaluated the effect of EHT on auditory comprehension, expressive communication, receptive language, cognition, and motor. EHT was found to be associated with a positive effect within the first year of life in these domains, as well as in the second and third year of life. Additionally, three novel at\u2010risk biomarkers were identified in this cohort: feeding difficulties in infancy, positional torticollis, and the need for orthotics. The positive effects of EHT observed in language, cognition, and motor at variable stages within the first 3\u2009years of life provide additional evidence into the possible efficacy of early biological treatment for boys with 47,XXY to address the neurodevelopmental dysfunction.<\/jats:p>","DOI":"10.1002\/ajmg.a.61561","type":"journal-article","created":{"date-parts":[[2020,3,27]],"date-time":"2020-03-27T09:20:14Z","timestamp":1585300814000},"page":"1881-1889","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Neurodevelopmental outcome of prenatally diagnosed boys with 47,<scp>XXY<\/scp> (Klinefelter syndrome) and the potential influence of early hormonal therapy"],"prefix":"10.1002","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9941-0568","authenticated-orcid":false,"given":"Carole A.","family":"Samango\u2010Sprouse","sequence":"first","affiliation":[{"name":"Department of Pediatrics, George Washington University  Washington District of Columbia USA"},{"name":"Department of Human and Molecular Genetics, Florida International University  Miami Florida USA"},{"name":"Department of Research, The Focus Foundation  Davidsonville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selena L.","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Research, The Focus Foundation  Davidsonville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia C.","family":"Lasutschinkow","sequence":"additional","affiliation":[{"name":"Department of Research, The Focus Foundation  Davidsonville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Sadeghin","sequence":"additional","affiliation":[{"name":"Department of Research, The Focus Foundation  Davidsonville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherida","family":"Powell","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, George Washington University  Washington District of Columbia USA"},{"name":"Department of Economics George Washington University  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francie L.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Research, The Focus Foundation  Davidsonville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Gropman","sequence":"additional","affiliation":[{"name":"Division of Neurogenetics and Developmental Pediatrics Children's National Health System  Washington District of Columbia USA"},{"name":"Department of Neurology George Washington University  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,3,27]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"Bayley scales of infant and toddler development (3rd ed.)","author":"Bayley N.","year":"2006"},{"issue":"4","key":"e_1_2_8_3_1","first-page":"192","article-title":"Klinefelter syndrome in clinical practice","volume":"4","author":"Bojesen A.","year":"2007","journal-title":"Nature Reviews Urology"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-0777"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-021491"},{"key":"e_1_2_8_6_1","volume-title":"Early Language Milestone Scale (ELM Scale\u20102)","author":"Coplan J.","year":"1993"},{"issue":"4","key":"e_1_2_8_7_1","first-page":"273","article-title":"Sex chromosome anomalies: Prenatal diagnosis and the need for continued prospective studies","volume":"26","author":"Evans J. 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