Brugada Syndrome in Myotonic Dystrophy Type 2: First Report of an ANK2 Variant
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Myotonic dystrophy type 2 (DM2) is an autosomal dominant multisystem disorder with known cardiac involvement, although associations with Brugada syndrome (BrS) are rare. BrS is a genetic arrhythmia syndrome characterized by ST-segment elevation in the right precordial leads and an increased risk of sudden cardiac death. While BrS is commonly linked to SCN5A mutations, other genes such as ANK2 have also been implicated. We report the case of a 70-year-old woman with genetically confirmed DM2 who presented with clinically significant ventricular arrhythmias and a Brugada-type ECG pattern induced by flecainide challenge. Genetic analysis confirmed a CNBP expansion, consistent with DM2. Whole-exome sequencing revealed a novel heterozygous ANK2 variant, c.37G>A (p.Gly13Arg), absent in BrS-related genes including SCN5A. In silico tools predicted this variant to be deleterious, occurring at a highly conserved site within a disordered, charge-rich protein region essential for ankyrin-B function. Our findings suggest a potential pathogenic role of ANK2 p.(Gly13Arg) in BrS and support the possibility of Brugada arrhythmias in DM2 patients. This is the first report of a BrS-associated ANK2 variant in a DM2 individual, expanding the genetic and clinical spectrum of both disorders.