CTG EXPANSION AND CARDIAC MANIFESTATION IN MYOTONIC DYSTROPHY

P. Melacini, E. Menegazzo*, C. Villanova, G. Novelli§, M.L. Mostacciuolo#, G. Rizzoli, M. Gennarelli§, G.F. Buja, M. Miorelli, C. Angelini*, B. Dallapiccola§, S. Dalla Volta.
Department of Cardiology, *Department of Neurology, #Department of Biology, University of Padova, §Department of Human Genetics, Tor Vergata University of Rome

The myotonic dystrophy (DM) mutation, identified as an unstable deoxyribonucleic acid (DNA) sequence prone to increase the number of trinucleotide repeats, produces clinical manifestations of the disease in the skeletal muscle, the heart and many organ systems.

Because sudden death due to complete atrioventricular (AV) block or ventricular arrhythmias is the most dramatic event in DM, we assessed the relation of cardiac disease to cytosine-thymine-guanine (CTG) triplet mutation in adult patients affected with DM 42 DM cases underwent electrocardiography, echocardiography, signal-averaging electrocardiography and 24-h Holter monitoring. The diagnosis was established by neurological examination, electromyography, muscle biopsy and DNA analysis. Patients were divided in 3 subgroups according to the entity of CTG expansions: E1 (CTG > 500 triplets), E2 (up to 1000 triplets), E3 + E4 (E3 = 1000 < CTG < 1500 triplets, E4 = CTG > 1500 triplets). The following variables were significantly different in the 3 subgroups:

 

E1
(18 pts)

E2
(12 pts)

E3 + E4
(10 + 2 pts)

b

EKG normal

55%

50%

17%*

0.39
cLBBB

5%

0%

42%**

10
ventricular late potentials

33%

70%

83%^

3.3
ventricular arrhythmias
(couplets and triplets)

0%

0%

29%§

---

cLBBB: complete left bundle branch block.

Mantel-Haenszel test: *:c 2 = 0.04, p for logistic trend > 0.04; **: c 2 = 0.01, p for logistic trend < 0.03; ^: c 2 = 0.04, p for logistic trend < 0.05; §: c 2 = 0.02. The age is not confounding factor.

Conclusion. Our findings suggest that the involvement of specialized cardiac tissue, accounting for severe AV and intraventricular conduction defects, is related to CTG repeat length. In addition, the presence of abnormal late potentials, caused by slowed and fragmented conduction through damaged areas of myocardium, represents a substrate for malignant reentrant ventricular arrhythmias. In the future, therefore, molecular analysis of DNA should identify patients with cardiac disease at high risk for development of AV block or lethal ventricular arrhythmias.

[Keywords: Myotonic Dystrophy, CTG / trinucleotide repeats, Arrhythmias]

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