Sudden cardiac death in J wave syndrome with short QT associated to a novel mutation in Nav 1.8 coding gene SCN10A: First case report for a possible pharmacogenomic role

• Published in: Journal of electrocardiology Vol. 51; no. 5; pp. 809 - 813
• Main Authors: Di Stolfo, Giuseppe, Palumbo, Pietro, Castellana, Stefano, Mastroianno, Sandra, Biagini, Tommaso, Palumbo, Orazio, Leone, Maria Pia, De Luca, Giovanni, Potenza, Domenico Rosario, Mazza, Tommaso, Russo, Aldo A., Carella, Massimo
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01-09-2018; Elsevier Science Ltd
• Subjects: Cardiovascular disease; Case reports; Genes; Genomics; Mortality; Mutation; Next generation sequencing; SCN10A; Sudden cardiac death; Sudden cardiac death; Next generation sequencing; SCN10A
• ISSN: 0022-0736; 1532-8430
• DOI: 10.1016/j.jelectrocard.2018.06.005

Sudden cardiac death is an important cause of mortality in the general population. It represents an important challenge for clinicians, often being the only symptom of a broad spectrum of cardiac pathologies and inherited heart conditions. Early repolarization syndrome and Brugada syndrome are part of the wider “J-wave” syndrome, which may also include the short QT syndrome as a third factor of an ionic channel imbalance in the arrhythmogenic landscape.
We describe the case of a woman struck down by sudden cardiac death, with short QT and early repolarization, in which we found an extremely rare and putatively pathogenic heterozygous variant in the SCN10A gene. Variants involving SCN10A, which encodes a voltage-gated sodium channel, were already associated with alterations of cardiac conduction parameters and the cardiac rhythm disorder, thereby influencing the cardiac physiology and predisposing to arrhythmia.
We underline the role of genetic predisposition to sudden cardiac death and, for the first time, suggest a possible environmental effect, such as a pharmacological therapy in the setting of sudden death, with the purpose to increase awareness in clinical practice.
•Sudden cardiac death is an important cause of mortality in the general population.•The p.Gly805Val of SCN10A variant is located within the transmembrane domain, which is interested by other disease causing mutations.•PGE2 plays a key-role in a PKA mediated process of NaV1.8 intracellular trafficking. This pathway could be decreased by COX-2 inhibitors.