title: The diagnostic and therapeutic aspects of loss-of-function cardiac sodium channelopathies in children.
abstract: BACKGROUND
  Loss-of-function sodium channelopathies manifest as a spectrum of diseases including Brugada syndrome (BrS) and cardiac conduction disease.
  
  
  OBJECTIVE
  To analyze the diagnostic and therapeutic aspects of these disorders in children.
  
  
  METHODS
  Patients aged ≤ 16 years with genetically confirmed loss-of-function sodium channelopathies (SCN5A mutation), presenting with cardiac symptoms, positive family history, and/or abnormal electrocardiogram (ECG), were included. Abnormal ECG consisted of type 1 BrS ECG and/or prolonged conduction intervals (PR interval/QRS duration > 98th percentile for age).
  
  
  RESULTS
  Among the cohort (n = 33, age 6 ± 5 years, 58% male subjects, 30% probands), 14 (42%) patients were symptomatic, presenting with syncope (n = 5), palpitations (n = 1), supraventricular arrhythmias (n = 3), aborted cardiac arrest (n = 3), and sudden cardiac death (n = 2). Heart rate was 91 ± 26 beats/min, PR interval 168 ± 35 ms, QRS duration 112 ± 20 ms, and heart-rate corrected QT interval 409 ± 26 ms. Conduction intervals were prolonged in 28 (85%) patients; 6 of these patients also had spontaneous type 1 BrS ECG. Eight fever-associated events occurred in 6 patients; 2 of these were vaccination-related fever episodes. Treatment included aggressive antipyretics during fever in all patients; antiarrhythmic treatment included implantable cardioverter-defibrillator (n = 4), pacemaker (n = 2), and beta-blockers, either alone (n = 3) or in combination with device (n = 2). During follow-up (4 ± 4 years), 2 previously symptomatic patients had monomorphic ventricular tachycardia; there were no deaths.
  
  
  CONCLUSIONS
  Diagnosis of loss-of-function sodium channelopathies in children relies on cardiac symptoms, family history, and ECG. Fever and vaccination are potential arrhythmia triggers; conduction delay is the commonest finding on ECG. Beta-blockers have a role in preventing tachycardia-induced arrhythmias; implantable cardioverter-defibrillator should probably be reserved for severe cases.
authors.affiliation: Department of Pediatric Cardiology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Priya
authors.initials: P
authors.lastname: Chockalingam
authors.forename: Sally-Ann B
authors.initials: SA
authors.lastname: Clur
authors.forename: Johannes M P J
authors.initials: JM
authors.lastname: Breur
authors.forename: Thomas
authors.initials: T
authors.lastname: Kriebel
authors.forename: Thomas
authors.initials: T
authors.lastname: Paul
authors.forename: Lukas A
authors.initials: LA
authors.lastname: Rammeloo
authors.forename: Arthur A M
authors.initials: AA
authors.lastname: Wilde
authors.forename: Nico A
authors.initials: NA
authors.lastname: Blom
mesh_terms: D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D053840:Brugada Syndrome / Q000175:diagnosis* / Q000503:physiopathology / Q000628:therapy; D053447:Channelopathies / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D017147:Defibrillators, Implantable; D003937:Diagnosis, Differential; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010138:Pacemaker, Artificial; D012189:Retrospective Studies; D012964:Sodium / Q000378:metabolism*
chemical_list: D000319:Adrenergic beta-Antagonists; D012964:Sodium