TY - JOUR
T1 - Loss-of-Function Sodium Channel Mutations in Infancy A Pattern Unfolds
AU - Chockalingam, Priya
AU - Wilde, Arthur A. M.
PY - 2012
Y1 - 2012
N2 - The role of channelopathies in the pathogenesis of sudden cardiac death (SCD) in patients with structurally normal hearts is a rapidly evolving story.(1) Many ion channels are involved, including loss-of-function sodium channelopathies of which the phenotypic spectrum ranges from lethal arrhythmias to asymptomatic carriers and includes Brugada Syndrome (BrS), cardiac conduction disease, sick sinus syndrome, atrial fibrillation and dilated cardiomyopathy. BrS, characterized by right precordial ST elevation on the electrocardiogram, is frequently associated with conduction delay, potentially lethal arrhythmias, and a positive family history of sudden premature death. BrS is estimated to be responsible for approximately 4% of all sudden deaths and 20% of sudden deaths in patients with structurally normal hearts. Despite an overall prevalence of about 5/10000 individuals,(2) BrS is considered extremely rare in the pediatric population. However, children harboring loss-of-function mutations in the gene coding for the sodium channel alpha-subunit (SCN5A) have been reported to present with life-threatening arrhythmias especially during febrile episodes.(3) While SCN5A mutations account for 11-28% of BrS probands, mutations of the L-type calcium channel (LTCC), including the gene coding for the LTCC beta-subunit (CaCNB2) among others, have recently been implicated in about 13% of patients with BrS-related phenotypes and SCD.(4) (SELECT FULL TEXT TO CONTINUE)
AB - The role of channelopathies in the pathogenesis of sudden cardiac death (SCD) in patients with structurally normal hearts is a rapidly evolving story.(1) Many ion channels are involved, including loss-of-function sodium channelopathies of which the phenotypic spectrum ranges from lethal arrhythmias to asymptomatic carriers and includes Brugada Syndrome (BrS), cardiac conduction disease, sick sinus syndrome, atrial fibrillation and dilated cardiomyopathy. BrS, characterized by right precordial ST elevation on the electrocardiogram, is frequently associated with conduction delay, potentially lethal arrhythmias, and a positive family history of sudden premature death. BrS is estimated to be responsible for approximately 4% of all sudden deaths and 20% of sudden deaths in patients with structurally normal hearts. Despite an overall prevalence of about 5/10000 individuals,(2) BrS is considered extremely rare in the pediatric population. However, children harboring loss-of-function mutations in the gene coding for the sodium channel alpha-subunit (SCN5A) have been reported to present with life-threatening arrhythmias especially during febrile episodes.(3) While SCN5A mutations account for 11-28% of BrS probands, mutations of the L-type calcium channel (LTCC), including the gene coding for the LTCC beta-subunit (CaCNB2) among others, have recently been implicated in about 13% of patients with BrS-related phenotypes and SCD.(4) (SELECT FULL TEXT TO CONTINUE)
U2 - https://doi.org/10.1161/CIRCULATIONAHA.111.071837
DO - https://doi.org/10.1161/CIRCULATIONAHA.111.071837
M3 - Editorial
C2 - 22090165
SN - 0009-7322
VL - 125
SP - 6
EP - 8
JO - Circulation
JF - Circulation
IS - 1
ER -