2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-QTc Prolongation in Rett Syndrome: Correlation with Genotype

QTc Prolongation in Rett Syndrome: Correlation with Genotype

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Rett syndrome (RTT) is a neurodevelopmental disorder associated with mutations in the MECP2 gene. Patients with RTT often experience abnormal electrocardiogram (ECG) and cardiac rhythm patterns, including a prolonged corrected QT interval (QTc), which increases the risk of sudden death. The purpose of this study was to investigate the relationship between QTc prolongation and specific mutation types in the MECP2 gene in a large cohort of RTT patients.<br /><br />The study analyzed data from the US Rett Natural History Study (RNHS) Cohort, which included 554 females and 2 males with RTT. The 15 most common single MECP2 gene mutations were evaluated, and ECG records were examined to determine the prevalence of prolonged QTc.<br /><br />The findings showed that 31% of all RTT patients in the cohort had at least one recorded ECG with prolonged QTc. Among patients with the R255X mutation, which was the most common mutation in the cohort, 41.8% had at least one recorded ECG with prolonged QTc. Statistically significant associations were found between the R255X mutation and prolonged QTc.<br /><br />The study supports current recommendations for baseline ECG and annual follow-up ECG in RTT patients and emphasizes the importance of closely monitoring medications in these patients. Patients with the R255X mutation should be given particular attention due to the presence of QTc prolongation.<br /><br />One limitation of the study was the absence of ECG records for many patients in the RNHS cohort. Future research should explore the association of prolonged QTc with age, clinical severity score, and concomitant medications.<br /><br />In conclusion, this study found a significant association between the R255X mutation in the MECP2 gene and prolonged QTc in RTT patients. These findings provide important insights into the cardiac manifestations of RTT and highlight the need for continued monitoring and intervention in this patient population.

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Presenting Author - Evdokia Angelidis, rising MD; Co-Author - Arthur A. Beisang, MD; Co-Author - Timothy A. Benke, MD PhD; Co-Author - Daniel G. Glaze, MD; Co-Author - Richard H. Haas, MD; Co-Author - Peter T. Heydemann, MD; Co-Author - Mary D. Jones, MD; Co-Author - Jane B. Lane, RN, BSN; Co-Author - David N. Lieberman, MD, PhD; Co-Author - Eric D. Marsh, MD, PhD; Co-Author - Jeffrey L. Neul, MD PhD; Co-Author - Sarika U. Peters, PhD; Co-Author - Robin C. Ryther, MD, PHD; Co-Author - Steven A. Skinner, MD; Co-Author - Shannon M. Standridge, DO, MPH; Co-Author - Walter E. Kaufmann, MD; Co-Author - Alan K. Percy, MD; Co-Author - Caroline B. Buchanan, MD;

Meta Tag

X-Inactivation/X-Linked Disease

Genotype-Phenotype Correlations

Databases

Congenital Anomaly

Chromosomal Abnormalities

Cardiovascular System

Cardiac/circulatory disorders

Co-Author Caroline B. Buchanan, MD

Co-Author Alan K. Percy, MD

Co-Author Walter E. Kaufmann, MD

Co-Author Shannon M. Standridge, DO, MPH

Co-Author Steven A. Skinner, MD

Co-Author Robin C. Ryther, MD, PHD

Co-Author Sarika U. Peters, PhD

Co-Author Jeffrey L. Neul, MD PhD

Co-Author Eric D. Marsh, MD, PhD

Co-Author David N. Lieberman, MD, PhD

Co-Author Jane B. Lane, RN, BSN

Co-Author Mary D. Jones, MD

Co-Author Peter T. Heydemann, MD

Co-Author Richard H. Haas, MD

Co-Author Daniel G. Glaze, MD

Co-Author Timothy A. Benke, MD PhD

Co-Author Arthur A. Beisang, MD

Presenting Author Evdokia Angelidis, rising MD

Keywords

Rett syndrome

neurodevelopmental disorder

MECP2 gene

abnormal electrocardiogram

prolonged corrected QT interval

sudden death risk

mutation types

RTT patients

prevalence of prolonged QTc

R255X mutation