{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:01:36Z","timestamp":1791388896973,"version":"4.3.3"},"reference-count":37,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T00:00:00Z","timestamp":1661385600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI 18\/01319"],"award-info":[{"award-number":["PI 18\/01319"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI18\/01319"],"award-info":[{"award-number":["PI18\/01319"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["21\/00248"],"award-info":[{"award-number":["21\/00248"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background and Objective<\/jats:title><jats:p>The objective of this study was to better delineate the genetic landscape and key clinical characteristics of complex, early\u2010onset, monogenic hyperkinetic movement disorders.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients were recruited from 14 international centers. Participating clinicians completed standardized proformas capturing demographic, clinical, and genetic data. Two pediatric movement disorder experts reviewed available video footage, classifying hyperkinetic movements according to published criteria.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>One hundred forty patients with pathogenic variants in 17 different genes (<jats:italic>ADCY5<\/jats:italic>, <jats:italic>ATP1A3<\/jats:italic>, <jats:italic>DDC<\/jats:italic>, <jats:italic>DHPR<\/jats:italic>, <jats:italic>FOXG1<\/jats:italic>, <jats:italic>GCH1<\/jats:italic>, <jats:italic>GNAO1<\/jats:italic>, <jats:italic>KMT2B<\/jats:italic>, <jats:italic>MICU1<\/jats:italic>, <jats:italic>NKX2<\/jats:italic>.<jats:italic>1<\/jats:italic>, <jats:italic>PDE10A<\/jats:italic>, <jats:italic>PTPS<\/jats:italic>, <jats:italic>SGCE<\/jats:italic>, <jats:italic>SLC2A1<\/jats:italic>, <jats:italic>SLC6A3<\/jats:italic>, <jats:italic>SPR<\/jats:italic>, and <jats:italic>TH<\/jats:italic>) were identified. In the majority, hyperkinetic movements were generalized (77%), with most patients (69%) manifesting combined motor semiologies. Parkinsonism\u2010dystonia was characteristic of primary neurotransmitter disorders (<jats:italic>DDC<\/jats:italic>, <jats:italic>DHPR<\/jats:italic>, <jats:italic>PTPS<\/jats:italic>, <jats:italic>SLC6A3<\/jats:italic>, <jats:italic>SPR<\/jats:italic>, <jats:italic>TH<\/jats:italic>); chorea predominated in <jats:italic>ADCY5<\/jats:italic>\u2010, <jats:italic>ATP1A3<\/jats:italic>\u2010, <jats:italic>FOXG1<\/jats:italic>\u2010, <jats:italic>NKX2<\/jats:italic>.<jats:italic>1<\/jats:italic>\u2010, <jats:italic>SLC2A1<\/jats:italic>\u2010, <jats:italic>GNAO1<\/jats:italic>\u2010, and <jats:italic>PDE10A<\/jats:italic>\u2010related disorders; and stereotypies were a prominent feature in <jats:italic>FOXG1<\/jats:italic>\u2010 and <jats:italic>GNAO1<\/jats:italic>\u2010related disease. Those with generalized hyperkinetic movements had an earlier disease onset than those with focal\/segmental distribution (2.5\u2009\u00b1\u20090.3 vs. 4.7\u2009\u00b1\u20090.7\u2009years; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.007). Patients with developmental delay also presented with hyperkinetic movements earlier than those with normal neurodevelopment (1.5\u2009\u00b1\u20092.9 vs. 4.7\u2009\u00b1\u20093.8\u2009years; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). Effective disease\u2010specific therapies included dopaminergic agents for neurotransmitters disorders, ketogenic diet for glucose transporter deficiency, and deep brain stimulation for <jats:italic>SGCE<\/jats:italic>\u2010, <jats:italic>KMT2B<\/jats:italic>\u2010, and <jats:italic>GNAO1<\/jats:italic>\u2010related hyperkinesia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study highlights the complex phenotypes observed in children with genetic hyperkinetic movement disorders that can lead to diagnostic difficulty. We provide a comprehensive analysis of motor semiology to guide physicians in the genetic investigation of these patients, to facilitate early diagnosis, precision medicine treatments, and genetic counseling. \u00a9 2022 The Authors. <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.29182","type":"journal-article","created":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T07:13:58Z","timestamp":1661411638000},"page":"2197-2209","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["The Genetic Landscape of Complex Childhood\u2010Onset Hyperkinetic Movement Disorders"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4979-2788","authenticated-orcid":false,"given":"Bel\u00e9n","family":"P\u00e9rez\u2010Due\u00f1as","sequence":"first","affiliation":[{"name":"Department of Pediatric Neurology Vall d'Hebron Hospital Universitary and Vall d'Hebr\u00f3n Research Institute (VHIR).  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