{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:13:20Z","timestamp":1792804400397,"version":"4.5.0"},"reference-count":25,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2013,10,31]],"date-time":"2013-10-31T00:00:00Z","timestamp":1383177600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001254","name":"Ipsen Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001254","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000380","name":"Guy's and St Thomas' Charity","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000380","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000317","name":"Action Medical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000317","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000304","name":"Parkinson's UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000304","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001279","name":"Great Ormond Street Hospital Charity","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001279","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Dystonia Society UK"},{"name":"Welsh Clinical Academic Track"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Develop Med Child Neuro"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Benign hereditary chorea is a dominantly inherited, childhood\u2010onset hyperkinetic movement disorder characterized by non\u2010progressive chorea and variable degrees of thyroid and respiratory involvement. Loss\u2010of\u2010function mutations in <jats:italic><jats:styled-content style=\"fixed-case\">NKX<\/jats:styled-content>2.1,<\/jats:italic> a gene vital to the normal development and function of the brain, lungs, and thyroid, have been identified in a number of individuals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>Clinical data from individuals with benign hereditary chorea identified through paediatric neurology services were collected in a standardized format. The <jats:italic><jats:styled-content style=\"fixed-case\">NKX<\/jats:styled-content>2.1<\/jats:italic> gene was analysed by Sanger sequencing, multiplex ligation\u2010dependent probe amplification, and microarray analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Six of our cohort were female and four male, median age at assessment was 8\u00a0years 6\u00a0months (range 1y 6mo\u201318y). We identified 10 probands with <jats:italic><jats:styled-content style=\"fixed-case\">NKX<\/jats:styled-content>2.1<\/jats:italic> mutations; nine of these mutations are novel (including two whole\u2010gene deletions) and one has been previously reported. Of the 10 individuals, eight presented with muscle hypotonia and four had evidence of hypothyroidism or respiratory involvement. Only three out of the 10 individuals had the full triad of \u2018brain\u2013lung\u2013thyroid syndrome\u2019 symptoms. Additional clinical characteristics occurring in individual participants included growth hormone deficiency, pes cavus, kyphosis, duplex kidney, and obsessive\u2013compulsive disorder.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our data suggest that the neurological phenotype is prominent in this condition and that many patients with benign hereditary chorea do not have the classic triad of brain\u2013lung\u2013thyroid syndrome. The extended phenotype may include obsessive\u2013compulsive disorder and skeletal abnormalities.<\/jats:p><\/jats:sec>","DOI":"10.1111\/dmcn.12323","type":"journal-article","created":{"date-parts":[[2013,10,31]],"date-time":"2013-10-31T11:24:06Z","timestamp":1383218646000},"page":"642-648","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Benign hereditary chorea related to <i><scp>NKX<\/scp>2.1<\/i>: expansion of the genotypic and phenotypic spectrum"],"prefix":"10.1111","volume":"56","author":[{"given":"Kathryn J","family":"Peall","sequence":"first","affiliation":[{"name":"MRC Centre for Neuropsychiatric Genetics and Genomics Institute of Psychological Medicine &amp; Clinical Neurosciences Cardiff University Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Lumsden","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology Evelina Children's Hospital St Thomas' Hospital London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Kneen","sequence":"additional","affiliation":[{"name":"Roald Dahl EEG Department Alder Hey Children's Hospital Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh","family":"Madhu","sequence":"additional","affiliation":[{"name":"Roald Dahl EEG Department Alder Hey Children's Hospital Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deirdre","family":"Peake","sequence":"additional","affiliation":[{"name":"Royal Belfast Hospital for Sick Children Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances","family":"Gibbon","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology University Hospital of Wales Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilary","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Royal Gwent Hospital Newport UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammy","family":"Hedderly","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology Evelina Children's Hospital St Thomas' Hospital London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Meyer","sequence":"additional","affiliation":[{"name":"ICH\u2010Neurosciences Unit University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie A","family":"Robb","sequence":"additional","affiliation":[{"name":"Dubowitz Neuromuscular Centre Great Ormond Street Hospital London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Lynch","sequence":"additional","affiliation":[{"name":"Paediatric Neurology Children's University Hospital Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary D","family":"King","sequence":"additional","affiliation":[{"name":"Paediatric Neurology Children's University Hospital Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Pierre","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology Evelina Children's Hospital St Thomas' Hospital London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huw R","family":"Morris","sequence":"additional","affiliation":[{"name":"MRC Centre for Neuropsychiatric Genetics and Genomics Institute of Psychological Medicine &amp; Clinical Neurosciences Cardiff University Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz","family":"Jungbluth","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology Evelina Children's Hospital St Thomas' Hospital London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manju A","family":"Kurian","sequence":"additional","affiliation":[{"name":"ICH\u2010Neurosciences Unit University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,10,31]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.8.971"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2011.09.013"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199804303381817"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000164000.75046.CC"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0214341"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-004-1559-x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23065"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(67)80322-6"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.51.2.295"},{"key":"e_1_2_8_11_1","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1001\/jama.1973.03220410017004","article-title":"Benign familial chorea with onset in childhood","volume":"225","author":"Chun RW","year":"1973","journal-title":"JAMA"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21135"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22215"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22426"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2012-302505"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2011.01.002"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp162"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21692"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.113.4.1093"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws308"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004583-199511000-00008"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.13.5.357"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1086\/302725"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2008.0085"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2012.04287.x"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-012-6618-z"}],"container-title":["Developmental Medicine &amp; 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