Clinical phenotype and diagnosis of arrhythmogenic right ventricular cardiomyopathy in pediatric patients carrying desmosomal gene mutations

BACKGROUND Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease carrying a risk of sudden death. Information about the clinical features during childhood and the age at disease onset is scanty. OBJECTIVE The aim of the study was to describe the ARVC phenotype as its initial clinical manifestation in a pediatric population (<18 years) with desmosomal gene mutations. METHODS Fifty-three ARVC desmosomal gene mutation carriers (mean age 12.3 +/- 3.9 years) were investigated by electrocardiogram (ECG), signal-averaged ECG, 24-hour Holter, echocardiogram, and contrast-enhanced cardiac magnetic resonance (CMR). RESULTS None of the children <= 10 years old fulfilled the 1994 criteria, as opposed to six (33%) aged 11-14 years and eight aged > 14 years (42%). At the end of follow-up (9 +/- 7 years), 21 (40%) fulfilled the 1994 diagnostic criteria (mean age 16 +/- 4 years). By using the 2010 criteria in subjects aged <= 18 years, 53% were unaffected, versus 62% by using the traditional criteria. More than two-thirds of affected subjects had moderate-severe forms of the disease. Contrast-enhanced CMR was performed in 21 (40%); of 13 unaffected gene mutation carriers, six showed ARVC morphological and/or tissue abnormalities. CONCLUSION In pediatric ARVC mutation carriers, a diagnosis was achieved in 40% of cases, confirming that the disease usually develops during adolescence and young adulthood. The 2010 modified criteria seem to be more sensitive than the 1994 ones in identifying familial pediatric cases. Contrast-enhanced CMR can provide diagnostic information on gene mutation carriers not fulfilling either traditional or modified criteria. Management of asymptomatic gene mutation carriers remains the main clinical challenge.