A novel homozygous PPP1R13L frameshift variant in a child with syndromic dilated cardiomyopathy and fatal arrhythmia.

BACKGROUND

Dilated cardiomyopathy is a rare but severe myocardial disease in the paediatric population, often leading to heart failure, heart transplantation, or sudden cardiac death. Genetic factors are a major contributor to childhood dilated cardiomyopathy. Recently, biallelic variants in the PPP1R13L gene have been implicated in a novel syndromic form of early-onset dilated cardiomyopathy, characterised by cardiac dysfunction alongside variable ectodermal features.

CASE PRESENTATION: We report a 4-year-old boy who presented with decompensated heart failure and echocardiographic findings consistent with dilated cardiomyopathy. Syndromic features included sparse, dry hair, high anterior hairline, broad nasal bridge, and pointed teeth. Genetic analysis revealed a novel homozygous frameshift variant in the PPP1R13L gene (c.2368_2375dup; p. Pro793Glyfs*32), classified as pathogenic. The clinical course was complicated by recurrent ventricular arrhythmias and ultimately sudden cardiac death.

CONCLUSION

PPP1R13L-related cardiomyopathy should be considered in children with early-onset dilated cardiomyopathy and syndromic features. Early diagnosis is critical for clinical management, arrhythmia surveillance, and appropriate family counselling.