title: Subclinical myocardial dysfunction in Rett syndrome.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Neonatal Intensive Care Unit, University General Hospital, Azienda Ospedaliera Universitaria Senese, Viale M. Bracci 16, Siena, Italy. geniente@gmail.com
authors: Claudio
authors: C
authors: De Felice
authors: Silvia
authors: S
authors: Maffei
authors: Cinzia
authors: C
authors: Signorini
authors: Silvia
authors: S
authors: Leoncini
authors: Stefano
authors: S
authors: Lunghetti
authors: Giuseppe
authors: G
authors: Valacchi
authors: Maurizio
authors: M
authors: D'Esposito
authors: Stefania
authors: S
authors: Filosa
authors: Floriana
authors: F
authors: Della Ragione
authors: Gianfranco
authors: G
authors: Butera
authors: Roberto
authors: R
authors: Favilli
authors: Lucia
authors: L
authors: Ciccoli
authors: Joussef
authors: J
authors: Hayek
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002648:Child; D016001:Confidence Intervals; D005260:Female; D006305:Health Status Indicators; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D009206:Myocardium / Q000473:pathology*; D018384:Oxidative Stress; D010092:Oximetry; D015518:Rett Syndrome / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D018570:Risk Assessment; D013223:Statistics as Topic; D014463:Ultrasonography
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2