Cardiac Dysrhythmias, Cardiomyopathy and Muscular Dystrophy in Patients with Emery-Dreifuss Muscular Dystrophy and Limb-Girdle Muscular Dystrophy Type 1B

Abstract

Emery-Dreifuss muscular dystrophy (EDMD) and limb-girdle muscular dystrophy type 1B (LGMD1B) are characterized by cardiac dysrhythmias, late-onset cardiomyopathy, slowly progressive skeletal myopathy and contractures of the neck, elbows and ankles. The causative mutation is either in the emerin gene (X-linked recessive EDMD) or lamin A/C gene (autosomal dominant EDMD2 or LGMD1B). We report three cases of EDMD, EDMD2 and LGMD1B. A 14-yr-old boy showed limitation of cervical flexion and contractures of both elbows and ankles. Sinus arrest with junctional escape beats was noted. He was diagnosed as X-linked recessive EDMD (MIM 310300). A 28-yr-old female showed severe wasting and weakness of humeroperoneal muscles. Marked limitation of cervical flexion and contractures of both elbows and ankles were noted. Varying degrees of AV block were noted. She was diagnosed as autosomal dominant EDMD2 (MIM 181350). A 41-yr-old female had contractures of both ankles and limb-girdle type muscular dystrophy. ECG revealed atrial tachycardia with high grade AV block. She was diagnosed as autosomal dominant LGMD1B (MIM 159001). Cardiac dysrhythmias in EDMD and LGMD1B include AV block, bradycardia, atrial tachycardia, atrial fibrillation, and atrial standstill, causing sudden death necessitating pacemaker implantation. Cardiologists should know about these unusual genetic diseases with conduction defects, especially in young adults.

Lamin A/C haploinsufficiency causes dilated cardiomyopathy and apoptosis-triggered cardiac conduction system disease

“…Although a skeletal myopathy predominates in two of these disorders, some patients develop cardiac electrophysiologic disease, progressive left ventricular dysfunction and heart failure (11). Electrophysiologic defects usually precede DCM (12), and may be the only manifestation of cardiac involvement (13)]. Electrophysiologic abnormalities include sinus node dysfunction, progressive atrioventricular (AV) block, paroxysmal atrial fibrillation and ventricular arrhythmias [9,10,14].…”

“…Several mutations which should produce null alleles cause Emery-Dreifuss muscular dystrophy. While most missense mutations associated with these cardiac phenotypes are predicted to encode dominant negative alleles, at least one mutation [17] predicted to produce haploinsufficiency, causes familial DCM and conduction system disease [8,9,10,12,13].…”

Ventricular Arrhythmia in X-linked Emery-Dreifuss Muscular Dystrophy: A Lesson from an Autopsy Case

“…However, when we look into the previous studies, cardiac function in EDMD patients varies from normal to severe depression of ejection fraction at less than 20% (2,14,15). Whether the fatal arrhythmia in this case was caused by the arrhythmogenesis of degenerated cardiomyocytes or secondly through impaired cardiac function is still unknown, however, there is no doubt that myocardial fibrosis played a critical role in the development of the arrhythmia.…”

“…Cardiac involvement is the most critical manifestation of the two diseases, and it usually becomes evident as contractures and muscle weakness progress. Conduction abnormalities are often observed as ranging from sinus bradycardia, to prolongation of PR interval, to complete atrioventricular block, and thus pacemaker implantation has been encouraged to prevent sudden death (1,2,5).…”

“…It is characterized by the presence of slow, progressive muscle wasting and weakness, early contractures, and cardiacconductive disturbances (1)(2)(3)(4). Pacemaker implantation is encouraged to prevent sudden death from atrioventricular block or from sick sinus syndrome (1,2,5). In this case report, we present an autopsy of an X-linked EDMD patient who died from ventricular arrhythmia despite undergoing a previous pacemaker implantation.…”