CORRELATION BETWEEN CARDIAC INVOLVEMENT AND CTG TRINUCLEOTIDE REPEAT LENGTH IN MYOTONIC-DYSTROPHY

Objectives. Because sudden death due to complete atrioventricular (AV) block or ventricular arrhythmias is the most dramatic event in myoton ic dystrophy, we assessed the relation of cardiac disease to cytosine- thymine-guanine (CTG) triplet mutation in adults affected with myotoni c dystrophy. Background. The myotonic dystrophy mutation, identified a s an unstable deoxyribonucleic acid (DNA) sequence (CTG) prone to incr ease the number of trinucleotide repeats, produces clinical manifestat ions of the disease in skeletal muscle, the heart and many organ syste ms. Methods. Forty-two adult patients underwent electrocardiography an d echocardiography; in addition, signal-averaging electrocardiography was performed in 22, and 24-h Holter monitoring was recorded in 32. Th e diagnosis was established by neurologic examination, electromyograph y, muscle biopsy and DNA analysis. The patients were then classified i nto three subgroups on the basis of the number of CTG trinucleotide re peat expansions: E(1) = 18 patients with 0 to 500 CTG repeats; E(2) = 12 patients with up to 1,000 repeats; E(3) + E(4) = 10 patients with u p to 1,500 repeats and 2 patients with >1,500 repeats. Results. The in cidence of normal electrocardiographic (EGG) results was found to be s ignificantly different in the three subgroups (55%, 50%, 17% in E(1), E(2), E(3) + E(4), respectively, p = 0.04), with the highest values in the group with fewer repeat expansions. The incidence of complete lef t bundle branch block was also significantly different among the group s (5% in E(1), 0% in E(2), 42% in E(3) + E(4) p = 0.01) and was direct ly correlated with the size of the expansion. A time domain analysis o f the signal-averaged ECG obtained in 12 patients in E(1), 4 in E(2), 5 in E(3) and 1 in E(4) showed that abnormal ventricular late potentia ls were directly correlated with CTG expansion (33% in E(1), 75% in E( 2), 83% in E(3) + E(4), p = 0.05). Moreover, the incidence of ventricu lar couplets or triplets showed a positive correlation with size of CT G expansion (0 in E(1), 0 in E(2), 29% in E(3) + E(4) chi square 0.02) . Conclusions. Our findings suggest that the involvement of specialize d cardiac tissue, accounting for severe AV and intraventricular conduc tion defects, is related to CTG repeat length. In addition, the presen ce of abnormal late potentials directly correlates to CTG expansion. A bnormal late potentials, caused by slowed and fragmented conduction th rough damaged areas of myocardium, represent a substrate for malignant reentrant ventricular arrhythmias. In the future, therefore, molecula r analysis of DNA should identify patients with cardiac disease at hig h risk for development of AV block or Lethal ventricular arrhythmias.