{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T23:55:34Z","timestamp":1792108534069,"version":"4.4.0"},"reference-count":35,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,7,30]],"date-time":"2019-07-30T00:00:00Z","timestamp":1564444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS058949"],"award-info":[{"award-number":["R01NS058949"]}],"id":[{"id":"10.13039\/100000065","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":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Objectives<\/jats:title><jats:p>Rapid\u2010onset dystonia\u2013parkinsonism (RDP) is caused by mutations in the <jats:italic>ATP1A3<\/jats:italic> gene, which codes for the \u03b1\u20103 subunit of the Na<jats:sup>+<\/jats:sup>\/K<jats:sup>+<\/jats:sup> ATPase. It has been characterized by rapid\u2010onset bulbar dysfunction, limb dystonia, bradykinesia, and a rostrocaudal spatial gradient of expression, usually after a physiologic trigger. We reexamined whether these features were in fact characteristic.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We characterized phenotypic variation within a cohort of 50 <jats:italic>ATP1A3<\/jats:italic> mutation\u2010positive individuals (carriers) and 44 mutation\u2010negative family members (noncarriers). Potential participants were gathered through referral for clinical suspicion of RDP or alternating hemiplegia of childhood. Inclusion criteria were having a <jats:italic>ATP1A3<\/jats:italic> mutation or being a family member of such an individual.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found RDP is underdiagnosed if only \u201ccharacteristic\u201d patients are tested. Rapid onset and bulbar predominance were not universally present in carriers. Among those with at least mild symptoms of dystonia, rostrocaudal severity gradient was rare (7%). Symptoms began focally but progressed to be generalized (51%) or multifocal (49%). Arm (41%) onset was most common. Arms and voice were typically most severely affected (48% and 44%, respectively). Triggers preceded onset in 77% of the participants. Rapid onset, dystonia, parkinsonism, bulbar symptoms, headaches, seizures, frontal impairment, and a history of mood disorder and a history of psychosis were more common in carriers. Approximately half of the proband mutations occurred de novo (56%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings suggest that patients should not be excluded from <jats:italic>ATP1A3<\/jats:italic> testing because of slow onset, limb onset, absent family history, or onset in middle adulthood. RDP should be strongly considered in the differential for any bulbar dystonia. \u00a9 2019 International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.27801","type":"journal-article","created":{"date-parts":[[2019,7,30]],"date-time":"2019-07-30T10:14:21Z","timestamp":1564481661000},"page":"1528-1536","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Revising rapid\u2010onset dystonia\u2013parkinsonism: Broadening indications for <i>ATP1A3<\/i> testing"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8001-8440","authenticated-orcid":false,"given":"Ihtsham U.","family":"Haq","sequence":"first","affiliation":[{"name":"Department of Neurology Wake Forest School of Medicine  Winston\u2010Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverly M.","family":"Snively","sequence":"additional","affiliation":[{"name":"Department of Biostatistical Sciences Wake Forest School of Medicine  Winston\u2010Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen J.","family":"Sweadner","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia K.","family":"Suerken","sequence":"additional","affiliation":[{"name":"Department of Biostatistical Sciences Wake Forest School of Medicine  Winston\u2010Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared F.","family":"Cook","sequence":"additional","affiliation":[{"name":"Department of Neurology Wake Forest School of Medicine  Winston\u2010Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie J.","family":"Ozelius","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Neurology Wake Forest School of Medicine  Winston\u2010Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William V.","family":"McCall","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Health Behavior Medical College of Georgia August University  Augusta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher T.","family":"Whitlow","sequence":"additional","affiliation":[{"name":"Department of Radiology, Section of Neuroradiology Wake Forest School of Medicine  Winston\u2010Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Brashear","sequence":"additional","affiliation":[{"name":"Department of Neurology Wake Forest School of Medicine  Winston\u2010Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.12.2596"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl340"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.55.7.991"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.06.028"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.22524"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.11-02-00381.1991"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870110206"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.20695"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21335"},{"issue":"9","key":"e_1_2_8_11_1","first-page":"1030","article-title":"De novo mutations in ATP1A3 cause alternating hemiplegia of childhood","volume":"44","author":"Heinzen EL","year":"2012","journal-title":"NatGenet"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70182-5"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-9-15"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2017.04.022"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.12927"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000139"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.10377"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.20220"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(96)00231-6"},{"key":"e_1_2_8_20_1","volume-title":"Adjutant General's Office War Department. 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