title: Impact of clinical and genetic findings on the management of young patients with Brugada syndrome.
abstract: Brugada syndrome (BrS) is an arrhythmogenic disease associated with sudden cardiac death (SCD) that seldom manifests or is recognized in childhood.
  
  
  
  The objectives of this study were to describe the clinical presentation of pediatric BrS to identify prognostic factors for risk stratification and to propose a data-based approach management.
  
  
  
  We studied 106 patients younger than 19 years at diagnosis of BrS enrolled from 16 European hospitals.
  
  
  
  At diagnosis, BrS was spontaneous (n = 36, 34%) or drug-induced (n = 70, 66%). The mean age was 11.1 ± 5.7 years, and most patients were asymptomatic (family screening, (n = 67, 63%; incidental, n = 13, 12%), while 15 (14%) experienced syncope, 6(6%) aborted SCD or symptomatic ventricular tachycardia, and 5 (5%) other symptoms. During follow-up (median 54 months), 10 (9%) patients had life-threatening arrhythmias (LTA), including 3 (3%) deaths. Six (6%) experienced syncope and 4 (4%) supraventricular tachycardia. Fever triggered 27% of LTA events. An implantable cardioverter-defibrillator was implanted in 22 (21%), with major adverse events in 41%. Of the 11 (10%) patients treated with hydroquinidine, 8 remained asymptomatic. Genetic testing was performed in 75 (71%) patients, and SCN5A rare variants were identified in 58 (55%); 15 of 32 tested probands (47%) were genotype positive. Nine of 10 patients with LTA underwent genetic testing, and all were genotype positive, whereas the 17 SCN5A-negative patients remained asymptomatic. Spontaneous Brugada type 1 electrocardiographic (ECG) pattern (P = .005) and symptoms at diagnosis (P = .001) were predictors of LTA. Time to the first LTA event was shorter in patients with both symptoms at diagnosis and spontaneous Brugada type 1 ECG pattern (P = .006).
  
  
  
  Spontaneous Brugada type 1 ECG pattern and symptoms at diagnosis are predictors of LTA events in the young affected by BrS. The management of BrS should become age-specific, and prevention of SCD may involve genetic testing and aggressive use of antipyretics and quinidine, with risk-specific consideration for the implantable cardioverter-defibrillator.
authors.affiliation: CHU Nantes, Institut du Thorax, Nantes, France. Electronic address: antoine.andorin@gmail.com.
authors.forename: Antoine
authors.initials: A
authors.lastname: Andorin
authors.affiliation: Saint George's University of London, London, United Kingdom.
authors.forename: Elijah R
authors.initials: ER
authors.lastname: Behr
authors.affiliation: AP-HP, Hôpital Bichat, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Denjoy
authors.affiliation: Center for Cardiac Arrhythmias of Genetic Origin, IRCCS Istituto Auxologico Italiano, Milan, Italy; Department of Molecular Medicine, University of Pavia Pavia, Italy.
authors.forename: Lia
authors.initials: L
authors.lastname: Crotti
authors.affiliation: Center for Cardiac Arrhythmias of Genetic Origin, IRCCS Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Dagradi
authors.affiliation: CHU Strasbourg, Strasbourg, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Jesel
authors.affiliation: CHU Bordeaux, Hôpital Cardiologique du Haut Lévêque, Bordeaux, France.
authors.forename: Fréderic
authors.initials: F
authors.lastname: Sacher
authors.affiliation: CHR-GHSR La Réunion, Saint Pierre, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Petit
authors.affiliation: CHU Rennes, Hôpital Pontchaillou, Rennes, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Mabo
authors.affiliation: AP-HP, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Maltret
authors.affiliation: Saint George's University of London, London, United Kingdom.
authors.forename: Leonie C H
authors.initials: LC
authors.lastname: Wong
authors.affiliation: CHU Poitiers, Poitiers, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Degand
authors.affiliation: CHU Dijon, Dijon, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Bertaux
authors.affiliation: Hôpital des Enfants, Toulouse, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Maury
authors.affiliation: Hôpital des Enfants, Toulouse, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Dulac
authors.affiliation: CHU Nantes, Institut du Thorax, Nantes, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Delasalle
authors.affiliation: CHU Nantes, Institut du Thorax, Nantes, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Gourraud
authors.affiliation: CHU Tours, Hôpital Trousseau, Tours, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Babuty
authors.affiliation: Department of Pediatric Cardiology, Leiden University Medical Centre, Leiden, The Netherlands; Department of Pediatric Cardiology and.
authors.forename: Nico A
authors.initials: NA
authors.lastname: Blom
authors.affiliation: Center for Cardiac Arrhythmias of Genetic Origin, IRCCS Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Schwartz
authors.affiliation: Department of Clinical and Experimental Cardiology, Academic Medical Centre, Heart Centre, University of Amsterdam, Amsterdam, The Netherlands,; Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia.
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Wilde
authors.affiliation: CHU Nantes, Institut du Thorax, Nantes, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Probst
mesh_terms: D000293:Adolescent; D058070:Asymptomatic Diseases / Q000453:epidemiology; D053840:Brugada Syndrome / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D002648:Child; D016757:Death, Sudden, Cardiac / Q000209:etiology / Q000517:prevention & control; D017147:Defibrillators, Implantable; D004554:Electric Countershock / Q000295:instrumentation / Q000379:methods; D004562:Electrocardiography / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics*; D011379:Prognosis; D018570:Risk Assessment; D013575:Syncope / Q000209:etiology / Q000517:prevention & control; D017180:Tachycardia, Ventricular / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human
keywords: Arrhythmia; Brugada syndrome; Genetics; Pediatrics; Quinidine