Filamin C missense variant associated with severe right atrial disease and skeletal myopathy

INTRODUCTION: Filamin C (FLNC) gene variants associated with atrial cardiomyopathies have not been reported so far. The aim of this study was to assess the genetics of two siblings presenting with recurrent right atrial arrhythmias, severe right atrial dilatation, and skeletal myopathy.

METHODS: A family with subjects affected by recurrent atrial arrhythmias and skeletal myopathy was extensively evaluated by the means of electrocardiographic recordings, magnetic resonance, intracardiac high-density mapping, and genetic testing.

RESULTS: Two siblings with right atrial arrhythmias and severe right atrial disease were found to be heterozygous carriers of the variant FLNC-c.925G>A p.(Glu309Lys), previously reported as a variant of uncertain significance. Despite the presence of a severe dilatation of the right atrium in both patients, one presented with skeletal muscle myopathy and an atrial arrhythmia refractory to pharmacological and invasive treatment, while the other one did not have any myopathy, and rhythm control was easily achieved by drugs.

CONCLUSION: Filamin C missense variant c.925G>A p.(Glu309Lys) is associated with the severe right atrial disease. Considering cosegregation with the disease (PP1 supporting), this variant should be classified as likely pathogenic.