Mechanisms and management of the heart in myotonic dystrophy

Abstract

Myotonic dystrophy (DM) is the most common form of adult onset muscular dystrophy and is caused by expansion of short nucleotide repeats that, in turn, produce toxic RNA aggregates within cells. DM is multisystemic, and the heart is primary site of pathology. DM patients exhibit cardiac conduction disorders including atrial fibrillation, atrio-ventricular heart block and ventricular arrhythmias. DM patients are also at risk for cardiomyopathy and congestive heart failure. Myotonic dystrophy is also characterized by myotonia, muscle weakness, and profound fatigue. The management of these symptoms requires input from the cardiologist and a team approach to minimize the debilitating aspects of the disorder and optimize cardiac function.

Conflict of interest statement

Competing Interests: None

The authors have no competing interests to declare.

Figures

Figure 1

A. DM1 is caused by an expansion in a CTG repeat on chromosome 19. Expansion to more than 100 copies is pathogenic. B. A CCTG repeat is expanded on chromosome 3 in DM2. C. Transcription of the repeated DNA sequences leads to RNA that forms hairpin structures that in turn bind splicing factors within the nucleus. D. Sequestration of the splicing factors CUBGP and MBNL lead to abnormal splicing of target genes. Abnormal splicing of the chloride channel gene (CLCN1) leads to myotonia. Abnormal splicing of TNNT2 contributes to cardiomyopathy.

Figure 2

Shown is an EKG from a 22 year old male with DM1 immediately post exercise showing exercise-induced atrial fibrillation.

Figure 3

Shown is an EKG from a 54 year old female with DM2 who experienced syncope and had ventricular tachycardia on noninvasive monitoring. An ICD was placed.

Figure 4

Proposed algorithm for cardiovascular management in DM. PM, pacemaker; ICD, implantable cardioverter defibrillator; WMA, wall motion abnormality; LGE, late gadolinium enhancement; BB, beta blocker; ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; CAD, coronary artery disease.