Early Identification of Prolonged QT Interval for Prevention of Sudden Infant Death.

Introduction: Long QT syndrome is the main arrhythmogenic disease responsible for sudden death in infants, especially in the first days of life. Performing an electrocardiogram in newborns could enable early diagnosis and adoption of therapeutic measures focused on preventing lethal arrhythmogenic events. However, the inclusion of an electrocardiogram in neonatal screening protocols still remains a matter of discussion. To comprehensively analyse the potential clinical value of performing an electrocardiogram and subsequent follow-up in a cohort of newborns. Methods: Electrocardiograms were performed in 685 neonates within the first week of life. One year follow-up was performed if QTc > 450 ms identified. Comprehensive genetic analysis using massive sequencing was performed in all cases with QTc > 470 ms. Results: We identified 54 neonates with QTc > 450 ms/ <470 ms; all normalized QTc values within 6 months. Eight cases had QTc > 480 ms at birth and, if persistent, pharmacological treatment was administrated during follow-up. A rare variant was identified as the potential cause of long QT syndrome in five cases. Three cases showed a family history of sudden arrhythmogenic death. Conclusions: Our prospective study identifies 0.14% of cases with a definite long QT, supporting implementation of electrocardiograms in routine pediatric protocols. It is an effective, simple and non-invasive approach that can help prevent sudden death in neonates and their relatives. Genetic analyses help to unravel the cause of arrhythmogenic disease in diagnosing neonates. Further, clinical assessment and genetic analysis of relatives allowed early identification of family members at risk of arrhythmias helping to adopt preventive personalized measures.

Pediatric Malignant Arrhythmias Caused by Rare Homozygous Genetic Variants in TRDN: A Comprehensive Interpretation.

Aim: To perform a comprehensive phenotype-genotype correlation of all rare variants in Triadin leading to malignant arrhythmias in pediatrics. Methods: Triadin knockout syndrome is a rare entity reported in pediatric population. This syndrome is caused by rare variants in the TRDN gene. Malignant ventricular arrhythmias and sudden cardiac death can be a primary manifestation of disease. Although pharmacological measures are effective, some patients require an implantable defibrillator due to high risk of arrhythmogenic episodes. Main Results: Fourteen rare genetic alterations in TRDN have been reported to date. All of these potentially pathogenic alterations are located in a specific area of TRDN, highlighting this hot spot as an arrhythmogenic gene region. Conclusions: Early recognition and comprehensive interpretation of alterations in Triadin are crucial to adopt preventive measures and avoid malignant arrhythmogenic episodes in pediatric population.