Evaluation of QTc in Rett syndrome: Correlation with age, severity, and genotype

Jane Crosson, Siddharth Srivastava, Genila M. Bibat, Siddharth Gupta, Aditi Kantipuly, Constance Smith-Hicks, Scott M. Myers, Abanti Sanyal, Gayane Yenokyan, Joel Brenner, Sakkubai R. Naidu

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1495-1501
Number of pages7
JournalAmerican Journal of Medical Genetics, Part A
Volume173
Issue number6
DOIs
StatePublished - Jun 2017

Keywords

  • QTc prolongation
  • Rett syndrome
  • genotype

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Evaluation of QTc in Rett syndrome: Correlation with age, severity, and genotype'. Together they form a unique fingerprint.

Cite this