Subclinical myocardial dysfunction in Rett syndrome

Claudio De Felice, Silvia Maffei, Cinzia Signorini, Silvia Leoncini, Stefano Lunghetti, Giuseppe Valacchi, Maurizio D'Esposito, Stefania Filosa, Floriana Della Ragione, Gianfranco Butera, Roberto Favilli, Lucia Ciccoli, Joussef Hayek

Research output: Contribution to journalArticlepeer-review


Aims: Rett syndrome (RTT) is a rare neurodevelopmental disorder frequently linked to methyl-CpG-binding protein 2 (MeCP2) gene mutations. RTT is associated with a 300-fold increased risk of sudden cardiac death. Rhythm abnormalities and cardiac dysautonomia do not to fully account for cardiac mortality. Conversely, heart function in RTT has not been explored to date. Recent data indicate a previously unrecognized role of MeCP2 in cardiomyocytes development. Besides, increased oxidative stress markers (OS) have been found in RTT. We hypothesized that (i) RTT patients present a subclinical biventricular dysfunction and (ii) the myocardial dysfunction correlate with OS. Methods and results: We evaluated typical (n = 72) and atypical (n = 20) RTT female and healthy controls (n = 92). Main outcome measurements were (i) echocardiographic biventricular systo-diastolic parameters; (ii) correlation between echocardiographic measures and OS levels, i.e. plasma and intra-erythrocyte non-protein-bound iron (NPBI) and plasma F2-Isoprostanes (F2-IsoPs). A significant reduction in longitudinal biventricular function (tricuspid annular plane systolic excursion, mitral annular plane systolic excursion, S′ of lateral and septal mitral annulus, S′ of tricuspidal annulus) was evidenced in RTT patients vs. controls. No significant changes in the LV ejection fraction were found. Peak-early filling parameters (E, E′ of lateral mitral annulus, E′ of tricuspidal annulus) and right ventricular systolic pressure were reduced. A-wave, E/A, and E/E′ were normal. OS markers were increased, but only F2-IsoPs correlated to LV systolic dysfunction. Conclusion: These data indicate a previously unrecognized subclinical systo-diastolic biventricular myocardial dysfunction in typical and atypical RTT patients. A reduced preload is evidenced. The biventricular dysfunction is partially related to OS damage. Published on behalf of the European Society of Cardiology. All rights reserved.

Original languageEnglish
Pages (from-to)339-345
Number of pages7
JournalEuropean Heart Journal Cardiovascular Imaging
Issue number4
Publication statusPublished - Apr 2012


  • Echocardiography
  • MeCP2
  • Myocardial function
  • Oxidative stress
  • Perfusion index
  • Rett syndrome

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Radiology Nuclear Medicine and imaging


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