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Myotonic dystrophy type 1 (DM1) is the most common form of muscular dystrophy affecting adults. The genetic basis of DM1 consists of a mutational expansion of a repetitive trinucleotide sequence (CTG). The number of triplets expansion divides patients in four categories related to the molecular changes (E1, E2, E3, E4). The pathogenic mechanisms of multi-systemic involvement of DM1 are still unclear. DM1 has been suspected to be due to premature aging, that is known to be sustained by increased free radicals levels and/or decreased antioxidants activities in neurodegenerative disorders. Recently, the gain-of-function at RNA level hypothesis has gained great attention, but oxidative stress might act in the disease progression. We have investigated 36 DM1 patients belonging to 22 unrelated families, 10 patients with other myotonic disorders (OMD) and 22 age-matched healthy controls from the clinical, biochemical and molecular point of view. Biochemical analysis detected blood levels of superoxide dismutase (SOD), malonilaldehyde (MDA), vitamin E (Vit E), hydroxyl radicals (OH) and total antioxidant system (TAS). Results revealed that DM1 patients showed significantly higher levels of SOD (+40%; MAL (+57%; RAD 2 (+106%; and TAS (+20%; than normal controls. Our data support the hypothesis of a pathogenic role of oxidative stress in DM1 and therefore confirm the detrimental role played by free radicals in this pathology and suggest the opportunity to undertake clinical trials with antioxidants in this disorder.

The autonomic nervous system has been evaluated in myotonic dystrophy with contradictory results and its relationship with heart disturbances remains unclear. Twenty-three patients with myotonic dystrophy type 1 were investigated by a battery of six cardiovascular autonomic tests and power spectral analysis of heart rate variability. Although 15 patients (65%) revealed abnormal or borderline results in some tests, only one patient had a definite autonomic damage, as indicated by two or more abnormal tests. As a group, myotonic dystrophy type 1 patients showed a significant reduction of heart rate variability during deep breathing (P < 0.0001). The exclusive involvement of parasympathetic tests suggests that a mild vagal dysfunction occurs in some myotonic dystrophy type 1 patients. The results indicate that such autonomic abnormalities are not: (1) part of a peripheral neuropathy; (2) related to cytosine-thymine-guanine repeat size or breathing pattern. Power spectral analysis showed a reduction of supine low-frequency band, which is, but not exclusively, a marker of sympathetic activity. It was inversely correlated to disease duration (P < 0.04), suggesting a progression as the disease advances. A low-frequency power, recorded after standing, was significantly associated (P < 0.02) with presence of heart involvement. Our findings suggest that a mixed, especially parasympathetic, autonomic dysfunction may occur in myotonic dystrophy type 1, although it is not a major finding. It could play a role in the occurrence of cardiac abnormalities, or increase the risk of sudden cardiovascular events.