{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T21:13:48Z","timestamp":1778274828189,"version":"3.51.4"},"reference-count":55,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background: Channelopathies represent a heterogeneous group of rare inherited cardiac diseases associated with life-threatening arrhythmias. Our knowledge of their epidemiology in childhood is limited. The aim of this study is to evaluate the epidemiology of pediatric channelopathies on a Mediterranean island (Crete, Greece). Methods: Retrospective study of children &lt; 18 years followed in the Regional Tertiary Pediatric Cardiology Unit during a 24-year period (2002\u20132025) and meeting the disease-specific diagnostic criteria. Results: A total of 43 children (32 families) were enrolled, corresponding to an average annual incidence of 1.43 (95% C.I.: 1.03\u20131.92) and a cumulative prevalence of 31.1 (95% C.I.: 22.1\u201342.5) cases per 100, 000 children, with significant regional incidence differences. Long QT syndrome (n = 38) was predominant; rare cases of Brugada syndrome (n = 3) and Catecholaminergic polymorphic tachycardia (n = 2) were recorded. The diagnosis was based on symptomatic presentation (n = 15, 35%), while asymptomatic patients (n = 28, 65%) were diagnosed during cascade family screening (n = 22, 51%) and preparticipation screening (n = 6, 14%). They represented the first diagnosis within affected families (index cases) in 21\/43 (49%) of cases. Genetic testing was performed in 35\/43 (81%) channelopathy cases and it was positive in 33\/43 (77%) of them, specifically in 30 out of 38 (79%) LQT cases with a genotype of LQT2 in 15 (39%), LQT1 in 10 (26%), LQT3 in one (3%) and LQT5 in two (5%) cases. Conclusions: The incidence of pediatric channelopathies on the Mediterranean island of Crete seems comparable to that reported in the literature, with regional clusters of significantly increased incidence. Further study of the epidemiology of pediatric channelopathies is needed, to document any regional or ethnic differences and for the best design of large-scale screening programs.<\/jats:p>","DOI":"10.3390\/children13050659","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T20:11:13Z","timestamp":1778271073000},"page":"659","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Estimation of Incidence and Prevalence of Pediatric Channelopathies in a Mediterranean Population Based on a Single-Center, Retrospective Analysis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1822-1722","authenticated-orcid":false,"given":"Alena","family":"Bagkaki","sequence":"first","affiliation":[{"name":"School of Medicine, University of Crete, 71 003 Heraklion, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Papagiannis","sequence":"additional","affiliation":[{"name":"Onassis Cardiac Surgery Center, Syggrou Av. 356, 176 74 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aris","family":"Anastasakis","sequence":"additional","affiliation":[{"name":"Onassis Cardiac Surgery Center, Syggrou Av. 356, 176 74 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fragiskos","family":"Parthenakis","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Crete, 71 003 Heraklion, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory","family":"Chlouverakis","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Crete, 71 003 Heraklion, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8456-5292","authenticated-orcid":false,"given":"Emmanuil","family":"Galanakis","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Crete, 71 003 Heraklion, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5893-2121","authenticated-orcid":false,"given":"Ioannis","family":"Germanakis","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Crete, 71 003 Heraklion, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1097\/HCO.0b013e3282fcc2e3","article-title":"Ion channel diseases in children: Manifestations and management","volume":"23","author":"Schwartz","year":"2008","journal-title":"Curr. Opin. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1161\/CIRCULATIONAHA.109.863209","article-title":"Prevalence of the congenital long QT syndrome","volume":"120","author":"Schwartz","year":"2009","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/s41572-020-0188-7","article-title":"Inherited cardiac arrhythmias","volume":"6","author":"Schwartz","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/s41569-019-0266-2","article-title":"Epidemiology of inherited arrhythmias","volume":"17","author":"Offerhaus","year":"2019","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","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":"2018","journal-title":"Heart Lung Circ."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1056\/NEJMoa1510687","article-title":"A prospective study of sudden cardiac death among children and young adults","volume":"374","author":"Bagnall","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Salzillo, C., Ciccone, M.M., Introna, F., Santobuono, V.E., Solarino, B., and Marzullo, A. (2025). Sudden cardiac death in the young: Single-center study of Bari autopsy cases. Front. Cardiovasc. Med., 12.","DOI":"10.3389\/fcvm.2025.1630511"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1161\/CIRCEP.111.962019","article-title":"Long QT Syndrome: From genetics to management","volume":"5","author":"Schwartz","year":"2012","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.pediatrneurol.2013.03.017","article-title":"Arrhythmogenic channelopathy syndromes presenting as refractory epilepsy","volume":"49","author":"Hazle","year":"2013","journal-title":"Pediatr. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Gussak, I., and Antzelevitch, C. (2013). Cardiac Channelopathies and Sudden Infant Death Syndrome. Electrical Diseases of the Heart, Springer.","DOI":"10.1007\/978-1-4471-4978-1"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2490","DOI":"10.1093\/eurheartj\/ehw072","article-title":"Probability of diagnosing long QT syndrome in children and adolescents according to the criteria of the HRS\/EHRA\/APHRS expert consensus statement","volume":"37","author":"Yoshinaga","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1111\/j.1540-8159.2005.40020.x","article-title":"Prevalence and clinical course of the juveniles with Brugada-type ECG in Japanese population","volume":"28","author":"Oe","year":"2005","journal-title":"Pacing Clin. Electrophysiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1111\/ahg.12328","article-title":"Genetic history of the population of Crete","volume":"83","author":"Drineas","year":"2019","journal-title":"Ann. Hum. Gen."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Bagkaki, A., Parthenakis, F., Chlouverakis, G., Anastasakis, A., Papagiannis, I., Galanakis, E., and Germanakis, I. (2024). Epidemiology of Pediatric Cardiomyopathy in a Mediterranean Population. Children, 11.","DOI":"10.20944\/preprints202405.1075.v1"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3997","DOI":"10.1093\/eurheartj\/ehac262","article-title":"2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death Developed by 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 the Association for European Paediatric and Congenital Cardiology (AEPC)","volume":"43","author":"Zeppenfeld","year":"2022","journal-title":"Eur. Heart J."},{"key":"ref_16","first-page":"1601","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":"17","author":"Priori","year":"2015","journal-title":"Europace"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Bagkaki, A., Parthenakis, F., Chlouverakis, G., Galanakis, E., and Germanakis, I. (2024). Cardiovascular disease screening in Primary School Children. Children, 12.","DOI":"10.20944\/preprints202411.2307.v1"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1016\/j.hrthm.2008.03.037","article-title":"Accurate electrocardiographic assessment of the QT interval: Teach the tangent","volume":"5","author":"Postema","year":"2008","journal-title":"Heart Rhythm."},{"key":"ref_19","first-page":"353","article-title":"An Analysis of the Time-Relations of Electrocardiograms","volume":"7","author":"Bazett","year":"1920","journal-title":"Heart"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1161\/CIRCULATIONAHA.111.028258","article-title":"Derivation and validation of a simple exercise-based algorithm for prediction of genetic testing in relatives of LQTS probands","volume":"124","author":"Sy","year":"2011","journal-title":"Circulation"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1093\/eurjpc\/zwac081","article-title":"The influence of exercise and postural changes on ventricular repolarization in the long QT syndrome: A systematic scoping review","volume":"29","author":"Harvey","year":"2022","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_22","first-page":"e4","article-title":"EH-RA\/HRS\/APHRS\/LAHRS Expert Consensus Statement on the State of Genetic Testing for Cardiac Diseases","volume":"19","author":"Wilde","year":"2022","journal-title":"Heart Rhythm."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_24","doi-asserted-by":"crossref","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":"ref_25","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1161\/CIRCULATIONAHA.119.043132","article-title":"An International, Multicentered, Evidence-Based Reappraisal of Genes Reported to Cause Congenital Long QT Syndrome","volume":"141","author":"Adler","year":"2020","journal-title":"Circulation"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1093\/europace\/euw389","article-title":"The clinical and genetic spectrum of catecholaminergic ventricular tachycardia: Findings from an international multicenter registry","volume":"20","author":"Roston","year":"2018","journal-title":"Europace"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1016\/j.jacc.2018.06.037","article-title":"Present status of Brugada Syndrome","volume":"72","author":"Brugada","year":"2018","journal-title":"JACC"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1002\/humu.23730","article-title":"Genetic interpretation and clinical translation of minor genes related to Brugada syndrome","volume":"40","author":"Campuzano","year":"2019","journal-title":"Hum. Mutat."},{"key":"ref_29","unstructured":"(2025, September 23). Hellenic Statistical Authority Greece Population Data. Available online: https:\/\/www.statistics.gr\/el\/statistics\/-\/publication\/SPO18."},{"key":"ref_30","unstructured":"MedCalc Software Ltd (2025, September 02). Confidence Interval for a Rate. Available online: https:\/\/www.medcalc.org\/calc\/rate_comparison.php."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.3390\/clinpract14030082","article-title":"Early Screening for Long QT Syndrome and Cardiac Anomalies in Infants: A Comprehensive Study","volume":"14","author":"Nosetti","year":"2024","journal-title":"Clin. Pract."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1161\/CIRCEP.113.000619","article-title":"Electrocardiographic screening of 1-month-old infants for identifying prolonged QT intervals","volume":"6","author":"Yoshinaga","year":"2013","journal-title":"Circ. Arrhythmia Electrophysiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1159\/000511572","article-title":"Electrocardiographic Screening in the First Days of Life for Diagnosing Long QT Syndrome: Findings from a Birth Cohort Study in Germany","volume":"117","author":"Simma","year":"2020","journal-title":"Neonatology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1042\/CS20080528","article-title":"Long QT syndrome and associated gene mutation carriers in Japanese children: Results from ECG screening examinations","volume":"117","author":"Hayashi","year":"2009","journal-title":"Clin. Sci."},{"key":"ref_35","unstructured":"(2025, September 23). QT Drugs Lists. Available online: https:\/\/crediblemeds.org\/."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1093\/eurheartj\/ehaa605","article-title":"2020 ESC Guidelines on sports cardiology and exercise in patients with cardiovascular disease: The Task Force on sports cardiology and exercise in patients with cardiovascular disease of the European Society of Cardiology (ESC)","volume":"42","author":"Pelliccia","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Bagkaki, A., Tsoutsinos, A., Hatzidaki, E., Tzatzarakis, M., Parthenakis, F., and Germanakis, I. (2021). Mexiletine Treatment for Neonatal LQT3 Syndrome: Case Report and Literature Review. Front. Pediatr., 9.","DOI":"10.3389\/fped.2021.674041"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Balestra, E., Bobbo, M., Cittar, M., Chicco, D., D\u2019Agata Mottolese, B., Barbi, E., and Caiffa, T. (2024). Congenital Long QT Syndrome in Children and Adolescents: A General Overview. Children, 11.","DOI":"10.3390\/children11050582"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Mariani, M.V., Pierucci, N., Fanisio, F., Laviola, D., Silvetti, G., Piro, A., La Fazia, V.M., Chimenti, C., Rebecchi, M., and Drago, F. (2024). Inherited Arrhythmias in the Pediatric Population: An Updated Overview. Medicina, 60.","DOI":"10.3390\/medicina60010094"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.tcm.2017.07.012","article-title":"Effect of age and gender on the QTc-interval in healthy individuals and patients with long-QT syndrome","volume":"28","author":"Vink","year":"2018","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1161\/CIRCULATIONAHA.116.021823","article-title":"Clinical aspects of type 3 long QT syndrome. An international multicenter study","volume":"134","author":"Wilde","year":"2016","journal-title":"Circulation"},{"key":"ref_42","doi-asserted-by":"crossref","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. Arrhythmia Electrophysiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1053\/euhj.2002.3274","article-title":"Guidelines for the interpretation of the neonatal electrocardiogram. A Task Force for the European Society of Cardiology","volume":"23","author":"Schwartz","year":"2002","journal-title":"Eur. Heart J."},{"key":"ref_44","first-page":"30","article-title":"Electrocardiographic Assessment and Genetic Analysis in Neonates: A Current Topic of Discussion","volume":"15","author":"Cesar","year":"2019","journal-title":"Curr. Cardiol. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"101978","DOI":"10.1016\/j.gde.2022.101978","article-title":"From diagnostic testing to precision medicine: The evolving role of genomics in cardiac channelopathies and cardiomyopathies in children","volume":"76","author":"Bidzimou","year":"2022","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"30623","DOI":"10.1074\/jbc.M104471200","article-title":"Brugada and Long QT-3 Syndrome Mutations of a Single Residue of the Cardiac Sodium Channel Confer Distinct Channel and Clinical Phenotypes","volume":"276","author":"Rivolta","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1159\/000350825","article-title":"Cascade Screening in Families with Inherited Cardiac Diseases Driven by Cardiologists: Feasibility and Nationwide Outcome in Long QT Syndrome","volume":"126","author":"Theilade","year":"2013","journal-title":"Cardiology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1136\/bjsports-2023-107357","article-title":"Causes of sudden cardiac arrest and death and the diagnostic yield of sport preparticipation screening in children","volume":"58","author":"Graziano","year":"2024","journal-title":"Br. J. Sports Med."},{"key":"ref_49","doi-asserted-by":"crossref","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":"ref_50","doi-asserted-by":"crossref","first-page":"e12537","DOI":"10.1111\/anec.12537","article-title":"Clinical aspects of the three major genetic forms of long QT syndrome (LQT1, LQT2, LQT3)","volume":"23","author":"Kutyifa","year":"2018","journal-title":"Ann. Noninvasive Electrocardiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1016\/j.jacc.2018.01.078","article-title":"Interplay Between Genetic Substrate, QTc Duration, and Arrhythmia Risk in Patients with Long QT Syndrome","volume":"71","author":"Mazzanti","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.hlc.2018.10.016","article-title":"An update on the diagnosis and management of catecholamine polymorphic ventricular tachycardia","volume":"28","author":"Pflaumer","year":"2019","journal-title":"Heart Lung Circ."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1017\/S1047951116000548","article-title":"Brugada syndrome in the paediatric population: A comprehensive approach to clinical manifestations, diagnosis, and management","volume":"26","author":"Chierchia","year":"2016","journal-title":"Cardiol. Young"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"164","DOI":"10.15420\/aer.2016:22:3","article-title":"Brugada syndrome: Defining the risk in asymptomatic patients","volume":"5","author":"Sieira","year":"2016","journal-title":"Arrhythmia Electrophysiol. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s00392-017-1094-1","article-title":"Short QT syndrome in pediatrics","volume":"106","author":"Pereira","year":"2017","journal-title":"Clin. Res. Cardiol."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/13\/5\/659\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T20:38:07Z","timestamp":1778272687000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/13\/5\/659"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,8]]},"references-count":55,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["children13050659"],"URL":"https:\/\/doi.org\/10.3390\/children13050659","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,8]]}}}