We studied a five-generation family, in which a CACNA1C variant c.2573G>A p.Arg858His co-segregates with syncope and cardiac arrest, documenting electrocardiographic data and cardiac symptomatology.
In 118 genetically-confirmed LQT2 patients (69 families, 62 KCNH2 mutations), the ECG parameters, Schwartz scores, and the incidence of cardiac events, defined as syncope, aborted cardiac arrest, and sudden cardiac death, were evaluated.
We identified compound heterozygous mutations in KCNQ1 in a 5-yr-old child with JLNS, who visited the hospital due to recurrent syncope and seizures and had congenital sensorineural deafness.
The patient affected by L955V suffered from recurrent syncope (QTc approximately 460 ms), and this mutation led to greatly reduced current and reduced KCNH2 protein in plasma membrane preparations.
The aims of this study were to test the hypothesis that syncope events in FMs are benign events and to compare clinical characteristics, triggers eliciting the syncope events, and long-term outcomes between FMs and those with LQT1 or LQT2 mutations from the international Long QT Syndrome Registry.
Hydroxyzine, a first generation H(1)-receptor antagonist, inhibits human ether-a-go-go-related gene (HERG) current and causes syncope in a patient with the HERG mutation.
Single-strand conformation polymorphism (SSCP) analysis and subsequent DNA sequence analysis have identified a KCNQ1 mutation in a family that were clinically conspicuous due to several syncopes and prolonged QTc intervals in the ECG.
In contrast, among LQT1 women, the onset of menopause was associated with a reduction in the risk for recurrent syncope (hazard ratio, 0.19; P=0.05; P=0.02 for genotype-by-menopause interaction).
Screening KCNQ1, KCNH2, and SCN5A genes in the proband, who presented with syncope, led to the identification of a heterozygous mutation (p.H258P) in KCNQ1.
This observation has implicated the C-loop region as being mechanistically important in the altered response to sympathetic stimulation known to put patients with LQT1 at risk of syncope and sudden cardiac death.
An I313K mutation within the selectivity filter of KCNQ1 results in a dominant-negative loss of channel function, leading to a long QT interval and subsequent syncope.
The QTc duration and the frequency of cardiac events (syncope and LQTS-related cardiac arrest/death) were similar among carriers with the five HERG mutations.
In a 32-year-old woman with marked QT prolongation (QTc=0.61 s) and repeated episodes of syncope, we identified a single pertinent base substitution (G to A at 1909) in HERG by genetic analysis.
Furthermore, a prior syncope [hazard ratio (HR), 4.05; 95% confidence interval (CI), 1.1 to 15.0; p = 0.03] or an ACA (HR, 11.7; 95% CI, 3.1 to 43.4; p = <0.001) identified children with an increased risk for recurrent cardiac events compared to asymptomatic LQT children.