Background and aim The PKP2 gene encodes the desmosomal protein Plakophilin-2, vital for cellular adhesion between cardiomyocytes. It is associated with classical Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), a cardiac disorder that can cause malignant ventricular arrhythmias and sudden cardiac death in the young. The 12-lead electrocardiogram (ECG) is an important tool for diagnosis of ARVC but ECG patterns in paediatric carriers of PKP2 variants have not been previously systematically assessed.
Methods The retrospective study enrolled paediatric (<18 years) PKP2 gene carriers referred to Great Ormond Street Hospital between 2005 and 2023. Their ECGs were analysed and compared with an age and gender-matched healthy population using paired two-tailed χ2-test. Results: 28 PKP2 variant carriers (54% females) were identified, of which 2 (7%) were diagnosed with ARVC at the time of the ECG, with a mean age of 13.6 +∕- 4.8 years. These were compared to 28 healthy controls (mean age of 12.7 +/- 4.4 years). 17 carriers (60%) had low QRS voltages in the lateral leads, compared to 4 controls (16%). Fractioned QRS complexes were seen in the lateral leads in 19 (67%) and in the septal leads in 20 (71%), compared to 1 and 2 controls (3.5% and 7%, respectively). Abnormal T wave inversion (TWI) for age was found in 54% of the patients (29% in lateral leads) and flat T waves in 22 patients (78%); but these were not statistically-significantly different to controls. Conclusions Paediatric carriers of PKP2 gene variants are more likely to have low QRS voltages and QRS fractionation in the lateral and anterior leads than normal controls, but the presence of abnormally inverted or flat T waves did not discriminate between gene carriers and controls. Our findings suggest that paediatric-specific ECG features may represent early phenotypic expression of PKP2 gene variants.
