Abstract 2195: Familial Dilated Cardiomyopathy with Conduction Disease Caused by a Lamin A/C Mutation: Efficacy of the Cardiac Resynchronization Therapy with a Defibrillator
Mutations in the gene encoding the nuclear membrane protein, lamin A/C, have been linked to familial dilated cardiomyopathy (DCM) combined with conduction disease. We screened the lamin A/C gene in a large Japanese family with a significant history of DCM and pacemaker implants (PMI). 14 family members were affected: 13 with bradyarrhythmias (11 with PMI) and 8 with congestive heart failure (CHF) including 3 cases of sudden cardiac death (SCD). In addition, 4 members died of cerebral embolism presumably associated with atrial fibrillation (AF). (Figure⇓) The 56-year-old male proband received a PMI due to AF with complete atrio-ventricular block at age 47. Because of progressively declining left ventricular (LV) function after PMI despite mild CHF symptoms, and recurrent episodes of syncope due to ventricular tachycardia (VT), his pacemaker was upgraded to a biventricular pacemaker-defibrillator at age 53. The treatment resulted in a remarkable improvement of LVEF (from 35% to 56%), a decrease in end-diastolic LV volume (from 140 ml to 99 ml) and VT suppression. Analysis of the lamin A/C gene revealed a two base-pair deletion mutation, c.908 909delCT, which leads to a frame-shift resulting in a truncated protein (a.C303fs/25). All the affected members were positive for the mutation. Thus, we identified a lamin A/C mutation in a large family with DCM and conduction disease. Given the underlying conduction abnormality and higher rate of life-threatening tachyarrhythmias in lamin A/C-related cardiomyopathy, cardiac resynchronization therapy with a defibrillator in an early stage of CHF would merit an improved cardiac performance along with the added potential of preventing SCD.