title: Evaluation of QTc in Rett syndrome: Correlation with age, severity, and genotype.
abstract: Rett syndrome (RTT) is caused by MECP2 mutations, resulting in various neurological symptoms. Prolonged corrected QT interval (QTc) is also reported and is a speculated cause of sudden death in RTT. The purpose of this study was to correlate QTc in RTT patients with age, clinical severity, and genotype. 100 RTT patients (98 females, 2 males) with MECP2 mutations underwent baseline neurological evaluation (KKI-RTT Severity Scale) and QTc measurement (standard 12 lead electrocardiogram) as part of our prospective natural history study. Mean QTc of the cohort was 422.6 msec, which did not exceed the normal values for age. 7/100 patients (7%) had QTc prolongation (>450 msec). There was a trend for increasing QTc with age and clinical severity (P = 0.09). No patients with R106C, R106W, R133C, R168*, R270*, R294*, R306C, R306H, and R306P mutations demonstrated QTc prolongation. There was a relatively high proportion of QTc prolongation in patients with R255* mutations (2/8, 25%) and large deletions (1/4, 25%). The overall presence of QTc prolongation did not correlate with mutation category (P = 0.52). Our findings demonstrate that in RTT, the prevalence of QTc prolongation is lower than previously reported. Hence, all RTT patients warrant baseline ECG; if QTc is prolonged, then cardiac followup is warranted. If initial QTc is normal, then annual ECGs, particularly in younger patients, may not be necessary. However, larger sample sizes are needed to solidify the association between QTc and age and clinical severity. The biological and clinical significance of mild QTc prolongation above the normative data remains undetermined.
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Jane
authors.initials: J
authors.lastname: Crosson
authors.affiliation: Department of Neurology, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Siddharth
authors.identifier: http://orcid.org/0000-0001-7008-1879
authors.initials: S
authors.lastname: Srivastava
authors.affiliation: Department of Neurogenetics, Kennedy Krieger Institute, Baltimore, Maryland.|Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Genila M
authors.initials: GM
authors.lastname: Bibat
authors.affiliation: Department of Neurogenetics, Kennedy Krieger Institute, Baltimore, Maryland.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Neurogenetics, Kennedy Krieger Institute, Baltimore, Maryland.
authors.forename: Aditi
authors.initials: A
authors.lastname: Kantipuly
authors.affiliation: Department of Neurogenetics, Kennedy Krieger Institute, Baltimore, Maryland.|Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland.|Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Constance
authors.initials: C
authors.lastname: Smith-Hicks
authors.affiliation: Autism & Developmental Institute, Geisinger Health System, Lewisburg, Pennsylvania.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Myers
authors.affiliation: Johns Hopkins Biostatistics Center, Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Abanti
authors.initials: A
authors.lastname: Sanyal
authors.affiliation: Johns Hopkins Biostatistics Center, Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Gayane
authors.initials: G
authors.lastname: Yenokyan
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Joel
authors.initials: J
authors.lastname: Brenner
authors.affiliation: Department of Neurogenetics, Kennedy Krieger Institute, Baltimore, Maryland.|Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland.|Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Sakkubai R
authors.initials: SR
authors.lastname: Naidu
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D016757:Death, Sudden, Cardiac; D004562:Electrocardiography; D005260:Female; D005838:Genotype; D006329:Heart Conduction System / Q000503:physiopathology; D006801:Humans; D007223:Infant; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D009154:Mutation; D015518:Rett Syndrome / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2
keywords: QTc prolongation; Rett syndrome; genotype