Cardiac Evaluation of Pediatric Relatives in Sudden Arrhythmic Death Syndrome

Abstract

Background-Sudden arrhythmic death syndrome defines a sudden unexpected and unexplained death despite comprehensive pathological and toxicological investigation. Previous studies have focused on evaluation of adult relatives. There is, however, a lack of data in children, leading to highly variable management. We sought to determine the clinical utility of cardiac evaluation in pediatric relatives of sudden arrhythmic death syndrome probands. Methods and Results-Retrospective review was undertaken of pediatric patients with a family history of sudden arrhythmic death syndrome assessed from 2010 to 2013 in 2 centers. Clinical history, cardiac, and genetic investigations were assessed, including diagnoses made after evaluation of adult relatives. A total of 112 pediatric relatives from 61 families were evaluated (median age at presentation, 8 years; range, 0.5-16 years). A probable diagnosis was made in 18 (29.5%) families: Brugada syndrome, 13/18 (72%); long QT syndrome, 3/18 (17%); and catecholaminergic polymorphic ventricular tachycardia, 2/18 (11%). Genetic testing identified mutations in 20% of Brugada syndrome (2/10) and 50% of long QT syndrome (1/2) and catecholaminergic polymorphic ventricular tachycardia families (1/2) who were tested. Pediatric evaluation diagnosed 6/112 relatives (5.4%), increasing to 7% (6/85) if only first-degree relatives were assessed. The only useful diagnostic tests were the 12-lead and exercise electrocardiograms and ajmaline provocation test. The median duration of follow-up was 2.1 years (range, 0.2-8.2 years) with no cardiac events. Conclusions-The yield of evaluating pediatric relatives is significant and higher when focused on first-degree relatives and on conditions usually expressed in childhood. We propose a management pathway for these children. (Circ Arrhythm Electrophysiol. 2014;7:800-806.)

Whole-Exome Molecular Autopsy After Exertion-Related Sudden Unexplained Death in the Young

“…Identification of a VUS result should not trigger familial testing of the decedent's surviving first-degree relatives who have a normal cardiac evaluation without careful counseling. 24,25 Specifically, the family must not conclude that a request for variant-specific testing of relatives implies that the root cause has been detected. Instead, the relatives must understand that an ambiguous variant has been found and that the VUS could be reclassified potentially, for example, if the VUS was determined to be a sporadic, de novo variant.…”

“…Comparison of victims with (n=7) and without (n=11) ultrarare VUS demonstrates no difference in clinical characteristics including age (14.3±4.6 and 13.5±2.3 years; P=0.65), sex (57% and 73% men; P=0.63), race (86% and 91% white; P=1.0), sudden death as the sentinel event (86% and 73%; P=1.0), and family history of cardiac events (42% and 10%; P=0. 25). Two of the decedents hosted mutations within the CALM2 gene.…”

Sudden Cardiac Death in the Young

“…50%) of disease in the tested population, enhancing the positive predictive value. This approach, termed cascade screening, is useful in families with known disease causing mutations and phenotypes, 134, 135 such as LQTS, as well as in cases of sudden unexplained death, 135-139 employing electrocardiographic, genetic or other techniques as appropriate. In one study employing a national registry, an average of 2.1 new cases were identified per each LQTS proband, 134 and observational studies have noted a high diagnostic yield of affected family members of victims of SCD and unexplained cardiac arrest, 137 although this has not been a uniform finding.…”

Impact of clinical and genetic findings on the management of young patients with Brugada syndrome

“…In our experience this risk was lower (2/70; 2 NSVT in 2 SCN5A carriers among 70 tests). Their use at a very young age appears questionable, however, due to the low risk of LTA in asymptomatic patients without a spontaneous type 1 ECG pattern and the potential arrhythmogenic risk and psychological impact of provocation tests 15 .…”