FINAL DIAGNOSIS: MYOTONIC DYSTROPHY
Myotonic dystrophy is the most common adult muscular dystrophy with a prevalence of 1 in 8000. There are three forms of the disease: congenital, which is symptomatic at birth or in the first year of life with respiratory or feeding difficulties; classic, with onset between 10 and 60 years; and minimal, with onset after 50 years and only manifesting cataracts, myotonia and a mild degree of muscle weakness. The gene defect is an expanded CTG trinucleotide repeat within the non-coding portion of the DM-1 gene which is located on chromosome 19 and codes for the myotonin-kinase protein. It has been shown that there is a reduction in transcripts of this gene in patients with disease that is tissue specific, affecting especially muscle, liver, and brain. Muscular weakness is apparent early in the neck muscles and distal limb muscles with weakness of the wrist extensors, finger flexors and intrinsic hand muscles. The palate, tongue, and pharyngeal muscles are also involved, producing a dysarthric speech and swallowing problems. The proximal muscles remain stronger throughout the course. Effects of the disease can be seen by age 5, through the phenomenon of myotonia. Myotonia is demonstrated by percussing the thenar eminence which results in a slow relaxation of hand grip followed by a forced voluntary closure. In addition to the effects on muscles there may also be cataracts, intellectual changes, hypersomnia, gonadal atrophy, insulin resistance, decreased esophageal and colonic motility, and cardiac disturbances. Some of these complications were seen in this patient with cataracts, slight gonadal atrophy, decreased esophageal motility, and cardiac disturbances.
Manifestations of the disease in the heart are common, with studies showing an overall incidence of ECG abnormalities ranging from 37 to 80%. The His-Purkinje system is primarily involved with prolongation of the PR interval, QRS duration, and His bundle to ventricle (HV) interval. Left and right bundle branch block are seen in equal numbers and vary from 5 to 25%. In one study the HV interval was increased in 56% of cases and the PR interval in 21-40%. Sinus bradycardia has been documented in 5 to 25%. Tachyarrhythmias are also described with atrial flutter and fibrillation found in up to 25%. Histologic changes can be seen in the conduction system. A study of 12 autopsy cases by Nguyen et al. found fibrosis in the sinus node in 6 cases, AV node in 7, AV bundle in 8, branches in 10, and ventricular myocardium in 11. There was fatty infiltration in the sinus node in 2 cases, AV node in 2, AV bundle in 6, bundle branches in 1 and ventricular myocardium in 9. Atrophy and lymphocyte infiltration were also seen in some cases. The most feared complication of these conduction defects is sudden death, which occurs infrequently. Symptoms of myocardial disease are less common than the conduction defects, although dilated cardiomyopathy has been well documented. In a review of 23 autopsy cases, cardiomegaly was noted in 8 (35%). Biventricular hypertrophy and four chamber dilation were found in 3 (25%) of 12 cases in a study by Nguyen et al., and there was no evidence of ischemia or other causes for the cardiomyopathy. Echocardiography has also shown mitral valve prolapse in 25-40% of patients. Thus, this patient had the more typical disease manifestations with right and left bundle branch block, AV block, and mitral regurgitation, but also had dilated cardiomyopathy which is less common. He also manifested histologic changes in the SA and AV nodes similar to those seen in autopsy series.
Correlation between disease severity and number of trinucleotide repeats is inconclusive. One study of 14 patients showed no correlation and another of 42 patients showed correlation with left bundle branch block and other ECG findings. A recent study of 24 myotonic dystrophy patients by Marchini, et al. with CTG repeats ranging from 50 to 2200 showed no correlation with the presence of muscular atrophy, respiratory insufficiency, cardiac abnormalities, diabetes, cataracts, sleep disorders, or hypogonadism. There was correlation with age of onset, muscular disability, intellectual quotient, and short term memory.
Contributed by David Newton, MD and Edward C. Klatt, MD