{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T05:54:01Z","timestamp":1781589241331,"version":"3.54.5"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"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. Cardiovasc. Med."],"abstract":"<jats:p>\n                    Polymorphic ventricular tachycardia (VT), particularly in the absence of structural heart disease, has a strong genetic foundation primarily rooted in mutations affecting cardiac ion channels and associated regulatory proteins. Here, we report two patients with polymorphic VT harboring potassium channel subfamily J member 2 (KCNJ2) gene mutations. The first case is a 13-year-old girl presenting with periodic paralysis, polymorphic VT, and a prolonged QT interval. She was sequentially treated with metoprolol, verapamil, amiodarone, moricizine, and mexiletine, along with three radiofrequency catheter ablation sessions, but the therapeutic effect was unsatisfactory. Genetic testing revealed a\n                    <jats:italic>de novo<\/jats:italic>\n                    c.406T\u2009&amp;gt;\u2009C (p.S136P) variant in the KCNJ2 gene. During a 10-year follow-up period, she never experienced syncope. The second patient is a 5-year-old boy presenting with thumb adduction, polymorphic VT, and a prolonged QT interval. He was treated sequentially with metoprolol and flecainide, and his premature ventricular contraction burden decreased significantly after flecainide therapy. Genetic testing identified a\n                    <jats:italic>de novo<\/jats:italic>\n                    c.652C\u2009&amp;gt;\u2009T (p.A218T) variant in the KCNJ2 gene. This case report updates our understanding of KCNJ2 gene mutations. Arrhythmias due to KCNJ2 mutations respond poorly to antiarrhythmic drugs, but flecainide may be a promising therapeutic option. Arrhythmias associated with KCNJ2 mutations tend to have a more benign clinical course, but identifying mutation carriers at risk of life-threatening arrhythmias remains challenging.\n                  <\/jats:p>","DOI":"10.3389\/fcvm.2026.1839923","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T05:37:30Z","timestamp":1781588250000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Polymorphic ventricular tachycardia with mutation in KCNJ2: case report"],"prefix":"10.3389","volume":"13","author":[{"given":"Cuizhen","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Cardiology, Shanghai Children\u2019s Hospital, School of Medicine, Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Children\u2019s Hospital, School of Medicine, Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuilan","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Children\u2019s Hospital, School of Medicine, Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Children\u2019s Hospital, School of Medicine, Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Children\u2019s Hospital, School of Medicine, Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1161\/CIRCULATIONAHA.121.055783","article-title":"Polymorphic ventricular tachycardia: terminology, mechanism, diagnosis, and emergency therapy","volume":"144","author":"Viskin","year":"2021","journal-title":"Circulation"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1093\/europace\/euac030","article-title":"European Heart Rhythm Association (EHRA)\/Heart Rhythm Society (HRS)\/Asia Pacific Heart Rhythm Society (APHRS)\/Latin American Heart Rhythm Society (LAHRS) expert consensus statement on the state of genetic testing for cardiac diseases","volume":"24","author":"Wilde","year":"2022","journal-title":"Europace"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1932","DOI":"10.1016\/j.hrthm.2013.05.014","article-title":"HRS\/EHRA\/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013","volume":"10","author":"Priori","year":"2013","journal-title":"Heart Rhythm"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1625","DOI":"10.1016\/S0140-6736(99)02107-8","article-title":"Long QT syndromes and torsade de pointes","volume":"354","author":"Viskin","year":"1999","journal-title":"Lancet"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1093\/cvr\/cvaa068","article-title":"Heritable arrhythmias associated with abnormal function of cardiac potassium channels","volume":"116","author":"Crotti","year":"2020","journal-title":"Cardiovasc Res"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1772","DOI":"10.1016\/j.jacc.2020.02.033","article-title":"Natural history and risk stratification in Andersen-Tawil syndrome type 1","volume":"75","author":"Mazzanti","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1512","DOI":"10.1161\/01.cir.91.5.1512","article-title":"Catecholaminergic polymorphic ventricular tachycardia in children. A 7-year follow-up of 21 patients","volume":"91","author":"Leenhardt","year":"1995","journal-title":"Circulation"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1093\/eurheartj\/ehab687","article-title":"Evaluation of gene validity for CPVT and short QT syndrome in sudden arrhythmic death","volume":"43","author":"Walsh","year":"2022","journal-title":"Eur Heart J"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1675","DOI":"10.1093\/europace\/eux351","article-title":"Different responses to exercise between Andersen-Tawil syndrome and catecholaminergic polymorphic ventricular tachycardia","volume":"20","author":"Inoue","year":"2018","journal-title":"Europace"},{"key":"B10","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/s0092-8674(01)00342-7","article-title":"Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen\u2019s syndrome","volume":"105","author":"Plaster","year":"2001","journal-title":"Cell"},{"key":"B11","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1080\/17431380410032490","article-title":"Andersen-Tawil syndrome: a model of clinical variability, pleiotropy, and genetic heterogeneity","author":"Donaldson","year":"2004","journal-title":"Ann Med"},{"key":"B12","doi-asserted-by":"publisher","first-page":"2720","DOI":"10.1161\/CIRCULATIONAHA.104.472498","article-title":"Electrocardiographic features in Andersen-Tawil syndrome patients with KCNJ2 mutations: characteristic T-U-wave patterns predict the KCNJ2 genotype","volume":"111","author":"Zhang","year":"2005","journal-title":"Circulation"},{"key":"B13","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1093\/cvr\/cvac118","article-title":"Molecular stratification of arrhythmogenic mechanisms in the Andersen Tawil syndrome","volume":"119","author":"Moreno-Manuel","year":"","journal-title":"Cardiovasc Res"},{"key":"B14","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1172\/JCI15183","article-title":"Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome)","volume":"110","author":"Tristani-Firouzi","year":"2002","journal-title":"J Clin Invest"},{"key":"B15","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/s12883-019-1322-6","article-title":"Identification of gene mutations in patients with primary periodic paralysis using targeted next-generation sequencing","volume":"19","author":"Luo","year":"2019","journal-title":"BMC Neurol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"51779","DOI":"10.1074\/jbc.M310278200","article-title":"Defective potassium channel Kir2.1 trafficking underlies Andersen-Tawil syndrome","volume":"278","author":"Bendahhou","year":"2003","journal-title":"J Biol Chem"},{"key":"B17","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1080\/19336950.2020.1857980","article-title":"The clinical and genetic heterogeneity analysis of five families with primary periodic paralysis","volume":"15","author":"Wang","year":"2021","journal-title":"Channels (Austin)"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e52","DOI":"10.1161\/CIRCRESAHA.123.323895","article-title":"Extracellular Kir2.1(C122Y) mutant upsets Kir2.1-PIP(2) bonds and is arrhythmogenic in Andersen-Tawil syndrome","volume":"134","author":"Cruz","year":"2024","journal-title":"Circ Res"},{"key":"B19","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1016\/j.hrthm.2006.12.031","article-title":"Flecainide for recurrent malignant ventricular arrhythmias in two siblings with Andersen-Tawil syndrome","volume":"4","author":"B\u00f6kenkamp","year":"2007","journal-title":"Heart Rhythm"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1093\/europace\/eun180","article-title":"Reduction of complex ventricular ectopy and improvement in exercise capacity with flecainide therapy in Andersen-Tawil syndrome","volume":"10","author":"Fox","year":"2008","journal-title":"Europace"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1537078","DOI":"10.3389\/fcvm.2025.1537078","article-title":"Case report: high efficacy of low-dose flecainide as an add-on therapy to a beta-blocker for treating a high burden of idiopathic ventricular arrhythmias in a juvenile athlete","volume":"12","author":"Christou","year":"2025","journal-title":"Front Cardiovasc Med"},{"key":"B22","doi-asserted-by":"publisher","first-page":"15631","DOI":"10.1073\/pnas.1004021107","article-title":"Flecainide increases Kir2.1 currents by interacting with cysteine 311, decreasing the polyamine-induced rectification","volume":"107","author":"Caballero","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B23","doi-asserted-by":"publisher","first-page":"992185","DOI":"10.3389\/fcvm.2022.992185","article-title":"Case report: mexiletine suppresses ventricular arrhythmias in Andersen-Tawil syndrome","volume":"9","author":"Yang","year":"2022","journal-title":"Front Cardiovasc Med"},{"key":"B24","doi-asserted-by":"publisher","first-page":"2793","DOI":"10.1093\/eurheartj\/ehv316","article-title":"2015 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: the task force for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC)","volume":"36","author":"Priori","year":"2015","journal-title":"Eur Heart J"},{"key":"B25","doi-asserted-by":"publisher","first-page":"2096","DOI":"10.1093\/eurheartj\/ehac134","article-title":"Cardiac sympathetic denervation in the prevention of genetically mediated life-threatening ventricular arrhythmias","volume":"43","author":"Schwartz","year":"2022","journal-title":"Eur Heart J"},{"key":"B26","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.hrthm.2005.11.026","article-title":"Cellular basis for electrocardiographic and arrhythmic manifestations of Andersen-Tawil syndrome (LQT7)","volume":"3","author":"Tsuboi","year":"2006","journal-title":"Heart Rhythm"},{"key":"B27","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1007\/s10840-021-01077-w","article-title":"Catheter ablation of frequent monomorphic ventricular arrhythmias in Andersen-Tawil syndrome: case report and focused literature review","volume":"66","author":"Keegan","year":"2023","journal-title":"J Interv Card Electrophysiol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1805","DOI":"10.1093\/europace\/eut160","article-title":"Cardiac characteristics and long-term outcome in Andersen-Tawil syndrome patients related to KCNJ2 mutation","volume":"15","author":"Delannoy","year":"2013","journal-title":"Europace"},{"key":"B29","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1159\/000526385","article-title":"Prolonged QT interval in athletes: distinguishing between pathology and physiology","volume":"147","author":"Christou","year":"2022","journal-title":"Cardiology"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1093\/europace\/eut272","article-title":"Executive summary: HRS\/EHRA\/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes","volume":"15","author":"Priori","year":"2013","journal-title":"Europace"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1839923\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T05:37:31Z","timestamp":1781588251000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1839923\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,16]]},"references-count":30,"alternative-id":["10.3389\/fcvm.2026.1839923"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2026.1839923","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,16]]},"article-number":"1839923"}}