{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T04:59:39Z","timestamp":1781067579166,"version":"3.54.1"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p>\n                    Neonatal long QT syndrome (LQTS) is associated with substantial mortality and poses significant therapeutic challenges, particularly in cases refractory to beta-blocker monotherapy. Mexiletine is established for LQT3 caused by\n                    <jats:italic>SCN5A<\/jats:italic>\n                    gain-of-function mutations, but its role in potassium-channel-related neonatal LQTS is limited. We present two neonates with LQTS refractory to nadolol monotherapy: one with a heterozygous pathogenic\n                    <jats:italic>SCN5A<\/jats:italic>\n                    c.5287G\u2009&amp;gt;\u2009A (p.Val1763Met) variant (LQT3), and one with a heterozygous\n                    <jats:italic>KCNQ1<\/jats:italic>\n                    exon 13\u201315 deletion (LQT1). In both cases, addition of mexiletine to nadolol was associated with QTc shortening, reduction in ectopic burden, and resolution of 2:1 atrioventricular conduction in Case 1; no adverse events were documented. We describe the clinical experience descriptively, without proposing a generalizable mechanistic claim regarding mexiletine outside LQT3. No ICD implantation was performed and no deaths occurred during follow-up. These observations support further evaluation of mexiletine as an adjunct in refractory neonatal LQTS, including non-LQT3 subtypes.\n                  <\/jats:p>","DOI":"10.3389\/fped.2026.1823685","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T04:27:23Z","timestamp":1781065643000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Nadolol\u2013mexiletine combination therapy for refractory neonatal long QT syndrome: a case series beyond sodium channelopathies"],"prefix":"10.3389","volume":"14","author":[{"given":"Jihye","family":"You","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Jeonbuk National University Children\u2019s Hospital","place":["Jeonju, Republic of Korea"]},{"name":"Research Institute of Clinical Medicine of Jeonbuk National University","place":["Jeonju, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Ho","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1093\/eurheartj\/ehaa769","article-title":"1970\u20132020: 50 years of research on the long QT syndrome\u2014from almost zero knowledge to precision medicine","volume":"42","author":"Schwartz","year":"2021","journal-title":"Eur Heart J"},{"key":"B2","doi-asserted-by":"publisher","first-page":"3109","DOI":"10.1093\/eurheartj\/eht089","article-title":"The long QT syndrome: a transatlantic clinical approach to diagnosis and therapy","volume":"34","author":"Schwartz","year":"2013","journal-title":"Eur Heart J"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1709","DOI":"10.1056\/NEJM199806113382401","article-title":"Prolongation of the QT interval and the sudden infant death syndrome","volume":"338","author":"Schwartz","year":"1998","journal-title":"N Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.hlc.2018.09.007","article-title":"Channelopathies that lead to sudden cardiac death: clinical and genetic aspects","volume":"28","author":"Skinner","year":"2019","journal-title":"Heart Lung Circ"},{"key":"B5","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.jacc.2013.04.044","article-title":"Impact of genetics on the clinical management of channelopathies","volume":"62","author":"Schwartz","year":"2013","journal-title":"J Am Coll Cardiol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1016\/j.jacc.2003.09.049","article-title":"Long QT syndrome in neonates: conduction disorders associated with HERG mutations and sinus bradycardia with KCNQ1 mutations","volume":"43","author":"Lupoglazoff","year":"2004","journal-title":"J Am Coll Cardiol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1161\/CIRCEP.109.882159","article-title":"Clinical characteristics and genetic background of congenital long-QT syndrome diagnosed in fetal, neonatal, and infantile life: a nationwide questionnaire survey in Japan","volume":"3","author":"Horigome","year":"2010","journal-title":"Circ Arrhythm Electrophysiol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e196","DOI":"10.3346\/jkms.2018.33.e196","article-title":"Retrospective genetic analysis of 200 cases of sudden infant death syndrome and its relationship with long QT syndrome in Korea","volume":"33","author":"Son","year":"2018","journal-title":"J Korean Med Sci"},{"key":"B9","doi-asserted-by":"publisher","first-page":"e009726","DOI":"10.1161\/CIRCEP.121.009726","article-title":"Management of congenital long-QT syndrome: commentary from the experts","volume":"14","author":"Kaufman","year":"2021","journal-title":"Circ Arrhythm Electrophysiol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1093\/europace\/euac082","article-title":"Effectiveness and safety of mexiletine in patients at risk for (recurrent) ventricular arrhythmias: a systematic review","volume":"24","author":"van der Ree","year":"2022","journal-title":"Europace"},{"key":"B11","doi-asserted-by":"publisher","first-page":"674041","DOI":"10.3389\/fped.2021.674041","article-title":"Mexiletine treatment for neonatal LQT3 syndrome: case report and literature review","volume":"9","author":"Bagkaki","year":"2021","journal-title":"Front Pediatr"},{"key":"B12","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1002\/joa3.12210","article-title":"Mexiletine infusion challenge test for neonatal long QT syndrome with 2:1 atrioventricular block","volume":"35","author":"Okuwaki","year":"2019","journal-title":"J Arrhythm"},{"key":"B13","doi-asserted-by":"publisher","first-page":"989","DOI":"10.36660\/abc.20210533","article-title":"Mexiletine in a newborn with type 3 long QT syndrome: when access is difficult","volume":"118","author":"Pereira","year":"2022","journal-title":"Arq Bras Cardiol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1592","DOI":"10.1111\/jce.15517","article-title":"Mexiletine effectively prevented refractory torsades de pointes and ventricular fibrillation in a patient with congenital type 2 long QT syndrome","volume":"33","author":"Nakashima","year":"2022","journal-title":"J Cardiovasc Electrophysiol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"344","DOI":"10.3345\/kjp.2017.60.11.344","article-title":"Neonatal arrhythmias: diagnosis, treatment, and clinical outcome","volume":"60","author":"Ban","year":"2017","journal-title":"Korean J Pediatr"},{"key":"B16","doi-asserted-by":"publisher","first-page":"771","DOI":"10.4070\/kcj.2022.0102","article-title":"The outcome of long QT syndrome, a Korean single center study","volume":"52","author":"Ahn","year":"2022","journal-title":"Korean Circ J"},{"key":"B17","doi-asserted-by":"publisher","first-page":"2092","DOI":"10.1016\/j.jacc.2012.07.046","article-title":"Not all beta-blockers are equal in the management of long QT syndrome types 1 and 2: higher recurrence of events under metoprolol","volume":"60","author":"Chockalingam","year":"2012","journal-title":"J Am Coll Cardiol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1016\/j.jelectrocard.2018.08.035","article-title":"The role of mexiletine in the management of long QT syndrome","volume":"51","author":"Li","year":"2018","journal-title":"J Electrocardiol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1093\/europace\/euaa143","article-title":"Defining the normal QT interval in newborns: the natural history and reference values for the first 4 weeks of life","volume":"23","author":"P\u00e6rregaard","year":"2021","journal-title":"Europace"},{"key":"B20","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1007\/s00431-025-06641-4","article-title":"Approach to prolonged QT interval in paediatric and neonatal patients","volume":"184","author":"Buratti","year":"2025","journal-title":"Eur J Pediatr"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1823685\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T04:27:47Z","timestamp":1781065667000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1823685\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,10]]},"references-count":20,"alternative-id":["10.3389\/fped.2026.1823685"],"URL":"https:\/\/doi.org\/10.3389\/fped.2026.1823685","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,10]]},"article-number":"1823685"}}