Rett syndrome is a severe neurodevelopmental disorder of unknown aetiology. A prolonged QT interval has been described previously in patients with Rett syndrome. To investigate QT prolongation and the presence of cardiac tachyarrhythmias in Rett syndrome electrocardiography and 24 hour Holter monitoring were performed prospectively in a cohort of 34 girls with Rett syndrome. The corrected QT value was prolonged in nine patients. Compared with a group of healthy controls of a similar age range, the patients with Rett syndrome had significantly longer corrected QT values. Clinical severity was not a predictor for prolonged QT intervals in the Rett syndrome cohort. The prolonged QT syndrome is a serious and potentially lethal cardiac disorder and should be considered in all girls with Rett syndrome.