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. 2023 Dec;14(6):446-452.
doi: 10.14740/cr1580. Epub 2023 Nov 3.

The Heart of Rett Syndrome: A Quantitative Analysis of Cardiac Repolarization

Michael P Collins  1   2 , Mark C Johnson  1 , Robin C Ryther  3 , Judith L Weisenberg  2 , Peter T Heydemann  4 , Colleen M Buhrfiend  4 , William A Scott  5 , Dallas M M Armstrong  5 , Haley M Kern  5 , Hoang H Nguyen  4   5
Affiliations

The Heart of Rett Syndrome: A Quantitative Analysis of Cardiac Repolarization

Michael P Collins et al. Cardiol Res. 2023 Dec.

Abstract

Background: Rett syndrome (RTT) is a developmental encephalopathy disorder that is associated with a high incidence of sudden death presumably from cardiorespiratory etiologies. Electrocardiogram (ECG) abnormalities, such as prolonged heart-rate corrected QT (QTc) interval, are markers of cardiac repolarization and are associated with potentially lethal ventricular arrhythmias. This study investigates the cardiac repolarization characteristics of RTT patients, including QTc and T-wave morphology characteristics.

Methods: A retrospective quantitative analysis on 110 RTT patients and 124 age and sex-matched healthy controls was conducted.

Results: RTT patients had longer QTc, more abnormal T-wave morphology, and greater heterogeneity of cardiac repolarization parameters compared to controls. Even RTT patients without prolonged QTc had more abnormal ECG and T-wave characteristics than controls. Among RTT patients, MECP2 patients had prolonged QTc compared to CDKL5 and FOXG1 patients. A subset of five RTT patients who died had normal QTc, but more abnormal T-wave morphology than the remaining RTT patients.

Conclusions: Cardiac repolarization abnormalities are present in RTT patients, even without long QTc. T-wave morphology is related to RTT genotype and may be predictive of mortality. These findings could be used to help the management and monitoring of RTT patients.

Keywords: Abnormal T wave; Cardiac repolarization; Electrocardiogram; Long QT; Rett syndrome; T-wave analysis; Ventricular repolarization.

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Conflict of interest statement

Each author declares that they do not have any competing interests pertaining to this study.

Figures

Figure 1
Figure 1
Depiction of the electrocardiographic measurements along with T-wave morphology characteristics seen in the study’s RTT patients. (a) Normal T wave. (b) Prolonged QT with prolonged JTp. (c) Asymmetric T wave. (d) Notched T wave. (e) Flat T wave. This ECG had the highest morphology combination score (MCS). ECG: electrocardiogram; RTT: Rett syndrome; JTp: time from the J point to the peak of the T wave.
Figure 2
Figure 2
Distribution of patients with and without repeated prolonged QTc on ECG by RTT genotype. The black bar is the percentage of patients with repeated prolonged QTc on ECG. The gray bar is the percentage of patients without repeated prolonged QTc (i.e., patients with only one prolonged QTc on ECG or patients with no prolonged QTc on ECG). For each column, the percentage of patients with repeated prolonged QTc and the percentage of patients without repeated prolonged QTc add up to 100%. Clinical: clinical RTT as defined in the text; Uncommon: identified mutations besides R106W, R133c, R168X, R255X, R270X, R294x, R306C, R306H, T158M; QTc: corrected QT; ECG: electrocardiogram; RTT: Rett syndrome.
See this image and copyright information in PMC

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