Cardiomyopathy with an LMNA Genetic Variant Affecting Three Consecutive Generations: A Case Series

Abstract

We report the case of a family afflicted with cardiac laminopathy who showed atrial fibrillation (AF) and complete atrioventricular block across three generations. Implantable cardioverter defibrillators (ICDs) implantation, or cardiac resynchronization therapy (CRT) were delivered to the three patients (proband; 61 years old, proband's mother: 84 years old, and proband's daughter; 38 years old) to prevent sudden cardiac death or suppress heart failure progression. A novel frameshift mutation (LMNA Exon 9: c.1550dupA;p. N518Efs*34) was found in all three cases through genetic testing, and this mutation may potentially result in the relatively late appearance of a phenotype of left ventricular systolic dysfunction.

Keywords: LMNA cardiomyopathy; atrial fibrillation; atrioventricular block; implantable cardioverter defibrillator; sudden cardiac death.

Figure 1.

(A) The family pedigree of laminopathy. The arrow indicates the proband. The filled circles indicate the affected family members. The “+” symbols indicate carriers of the LMNA variant. NPs indicate the individuals who did not take genetic testing. (B) Ventricular fibrillation recorded using intracardiac electrocardiogram. (C) A 12-lead ECG on admission. (D) Echocardiographic findings of the four-chamber (left) and short-axis (right) views at diastole (upper) and systole (lower).

Figure 2.

(A) Twelve-lead ECG before cardiac resynchronization therapy. (B) Twelve-lead ECG after cardiac resynchronization therapy. (C) Chest radiography after biventricular pacemaker implantation. (D) Echocardiographic findings of the four-chamber (left) and short-axis (right) views at diastole (upper) and systole (lower).

Figure 3.

(A) Twelve-lead ECG on admission. (B) Echocardiographic findings of the four-chamber (left) and short-axis (right) views at diastole (upper) and systole (lower). (C) Chest radiography on admission. (D) Twelve-lead ECG after catheter ablation for atrial fibrillation. (E) Voltage map of the left atrium (Red, green, yellow, and blue areas show low voltage zone, and purple area shows normal voltage zone). AP depicts anteroposterior; ECG: electrocardiogram, LIPV: left inferior pulmonary vein, LSPV: left superior pulmonary vein, PA: posteroanterior, RSPV: right superior pulmonary vein, RIPV: right inferior pulmonary vein. (F) Sanger sequencing of the proband and family members. Red arrows indicate the inserted A overlapped with G.