Arrhythmogenic right ventricular cardiomyopathy: asymptomatic to life threatening as illustrated by the cases of two sisters

Abstract

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disorder of unknown cause that is characterised by fibrofatty replacement, primarily of the right ventricular myocardium, which can lead to life-threatening arrhythmias. It is a disease with a very diverse phenotype. In the present article we describe two sisters, each with a different manifestation of this disorder. The first patient died suddenly at the age of 18 during exercise. Her 17-year-old sister did not have any abnormalities at first cardiac consultation, but a few years later she met several diagnostic criteria for ARVC and an internal cardioverter defibrillator was implanted. Genetic analysis identified a mutation in the plakophilin- 2 (PKP2) gene. Cardiac evaluation of a third sister did not reveal any abnormalities and no mutation in the PKP2 gene was found. Thus, ARVC can vary in its clinical presentation, not only between siblings but also in time. This raises difficulties for the physician for diagnosis, treatment and followup. It is important for the physician involved to consider this disease in patients with palpitations and syncope, especially when there is a family history of ARVC or unexplained sudden death. (Neth Heart J 2007;15:348-53.).

Keywords: cardiomyopathy; genetics; right ventricle; sudden death.

Figure 1

Electrocardiogram from the patient in case report 2, showing a sinus bradycardia with inverted T waves in leads V₁ to V₃.

Figure 2

Electrocardiogram of the patient in case report 2 showing premature ventricular complexes and ventricular couplets with a left bundle branch block configuration (LBBB) and left axis deviation, during maximal exercise.

Figure 3

Screening of the PKP2 gene shows a substitution of nucleotide ‘C’ for an ‘A’ at cDNA position 2421 (marked by an arrow) (NCBI ref: NM_004572.2) which causes premature termination of the PKP2 protein at position 807 (Q807X). Left panel shows the nucleotide sequence from a control (wild type).

Figure 4

The 'triangle of dysplasia' consisting of the right ventricular outflow tract (1), the apex (2) and the infundibulum (3). RA=right atrium, LA=left atrium.