Cardiac gene defects can cause sudden cardiac death in young people

Abstract

Background: In Europe, sudden cardiac death (SCD) is one of the most common causes of death. Although sudden cardiac death usually happens in older people, 5% to 10% of the affected individuals are young and apparently healthy. Sudden death in infants, children, and young adults is relatively rare, with an incidence of 1 to 5 per 100 000 persons per year. Nonetheless, up to 7000 asymptomatic children die in the USA each year, almost half of them without any warning signs or symptoms.

Method: Selective literature review.

Results: Although structural cardiovascular abnormalities explain most cases of sudden cardiac death in young people, the cause of death remains unexplained after autopsy in 10% to 30% of cases. Potentially lethal ion channel disorders (channelopathies) such as the long QT syndromes (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and the Brugada syndrome (BrS) may account for at least one-third of these unexplained cases. Most of these diseases are hereditary with autosomal-dominant transmission, i.e., there is a 50% chance that the children of affected individuals will be affected themselves.

Conclusions: Post-mortem genetic screening for sequence variations in cardiac ion channel genes has become an important forensic tool for elucidating the cause of sudden cardiac death. Moreover, it allows the identification of other family members bearing the previously undiagnosed gene defect, who can then undergo a cardiological evaluation if indicated by their clinical history.

Keywords: cardiological diagnosis; family history; ion channel disorder; molecular biology; sudden cardiac death.

Figure 1

Causes of sudden cardiac death in persons younger than 35 years in Italy from 1979 to 1998, adapted from (2); ARVC, arrhythmogenic right ventricular cardiomyopathy; CHD, coronary heart disease

Figure 2

Monitor electrocardiogram of a patient with implanted cardioverter defibrillator (ICD) a) with electrical storm in known arrhythmogenic right ventricular disorder and additional SCN5a mutation; b) the same patient with polymorphic ventricular tachycardia

Figure 3

12 lead ECG of a patient a) before and b) after administration of 1 mg/kg BW ajmalin i.v. fractionated over 10 min; development of the J-point elevation and descending ST segment elevation with negative T wave in right precordial leads that are typical of Brugada syndrome

Figure 4

Recommended algorithm for dealing with families affected by sudden cardiac death, adapted from (17)

Figure 5

Frequency and distribution of mutations of the ion channel genes in 49 unexplained sudden deaths, adapted from (18)

E-Figure 1

12-lead ECG of a patient with congenital long QT syndrome. The frequency-corrected QT interval is 621 ms (ECG writing speed 50 mm/s)

E-Figure 2

12-lead ECG of a patient with spontaneous unmasking of ECG changes that are typical for Brugada syndrome in the precordial leads (see also figure 3)