Next generation sequencing for molecular confirmation of hereditary sudden cardiac death syndromes / Confirmación diagnóstica molecular mediante secuenciación masiva de nueva generación ("next generation sequencing") en síndromes hereditarios de muerte súbita cardíaca

Hereditary sudden cardiac death syndromes comprise a wide range of diseases resulting from alteration in cardiac ion channels. Genes involved in these syndromes represent diverse mutations that cause the altered encoding of the diverse proteins constituting these channels, thus affecting directly the currents of the corresponding ions. In the present article we will briefly review how to arrive to a clinical diagnosis and we will present the results of molecular genetic studies made in Mexican subjects attending the SCD Syndromes Clinic of the National Institute of Cardiology of Mexico City.

Los síndromes hereditarios de muerte súbita cardíaca comprenden una amplia gama de enfermedades resultantes de la alteración en los canales iónicos cardíacos. Los genes implicados en estos síndromes presentan mutaciones que causan alteraciones de las diversas proteínas que constituyen estos canales y que, por lo tanto, afectan directamente a las diferentes corrientes iónicas. En el presente artículo se revisa brevemente la forma de llegar a un diagnóstico clínico de dichos síndromes y se presentan los resultados de los estudios genéticos moleculares realizados en sujetos mexicanos que asisten a la Clínica de Síndromes Hereditarios de Muerte Súbita del Instituto Nacional de Cardiología Ignacio Chávez.

Long QT Syndrome: a Korean Single Center Study

The long QT syndrome (LQTS) is a rare hereditary disorder in which affected individuals have a possibility of ventricular tachyarrhythmia and sudden cardiac death. We investigated 62 LQTS (QTc > or = 0.47 sec) and 19 family members whose genetic study revealed mutation of LQT gene. In the proband group, the modes of presentation were ECG abnormality (38.7%), aborted cardiac arrest (24.2%), and syncope or seizure (19.4%). Median age of initial symptom development was 10.5 yr. Genetic studies were performed in 61; and mutations were found in 40 cases (KCNQ1 in 19, KCNH2 in 10, SCN5A in 7, KCNJ2 in 3, and CACNA1C in 1). In the family group, the penetrance of LQT gene mutation was 57.9%. QTc was longer as patients had the history of syncope (P = 0.001), ventricular tachycardia (P = 0.017) and aborted arrest (P = 0.010). QTc longer than 0.508 sec could be a cut-off value for major cardiac events (sensitivity 0.806, specificity 0.600). Beta-blocker was frequently applied for treatment and had significant effects on reducing QTc (P = 0.007). Implantable cardioverter defibrillators were applied in 6 patients. Congenital LQTS is a potentially lethal disease. It shows various genetic mutations with low penetrance in Korean patients.