Cardiac Phenotype Associated with Two Heterozygous LMNA Variants

Background: Laminopathies are a heterogenous group of heritable diseases caused by variants in the Lamin A/C gene (LMNA). They manifest as cardiac and muscular myopathies, lipodystrophies, neuropathies, and progeria. Cardiac manifestations include dilated cardiomyopathy and arrhythmias. Case presentation: A Finnish woman in her 40s who was found to carry two heterozygous likely pathogenic (LP) variants in LMNA, c.1003C>T p.Arg335Trp and c.1303C>T p.Arg435Cys. She was diagnosed with dilated cardiomyopathy and received cardiac resynchronization therapy with a defibrillator. Conclusions: Double heterozygous LMNA variants are exceedingly rare. Even though the patient presented with two LP variants, the age of onset was typical, and the phenotype was not markedly more severe than in those with only one LP variant.