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The objective of the present study was the evaluation of heart rate variability, a marker of autonomic activity, in females affected by classic Rett syndrome and atypical variants for a possible explanation of the higher risk for sudden death observed in these subjects. Our study showed that girls with classic Rett syndrome had significantly lower heart rate variability and longer corrected QT intervals than in atypical Rett syndrome and age-matched healthy girls. Reduction of heart rate variability progresses with age and with the clinical stage of the syndrome. These results suggest the possible role of the progressive cardiac dysfunction in the sudden death associated with Rett syndrome. 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