Challenges of diagnosis of long-QT syndrome in children

Area of Science:

• Cardiology
• Clinical Genetics
• Molecular Cardiology

Background:

• Long QT Syndrome (LQTS) is a cardiac channelopathy associated with risk of ventricular arrhythmias and sudden cardiac death.
• Long QT Syndrome type 1 (LQT1) is typically caused by mutations in the KCNQ1 gene.
• Accurate genetic diagnosis is crucial for risk stratification and management of LQTS patients.

Observation:

• A family with a clinical diagnosis of LQT1 presented with characteristic ECG findings, including polymorphic ventricular extrasystoles and non-sustained polymorphic ventricular tachycardia.
• Exertional ECG monitoring revealed polymorphic ventricular tachycardia, specifically torsade de pointes.
• Holter monitoring confirmed episodes of polymorphic ventricular extrasystolies and non-sustained polymorphic ventricular tachycardia.

Findings:

• Direct sequencing of KCNQ1, HERG, and SCN5A genes was performed on affected individuals.
• No mutations or polymorphisms were identified in the screened genes (KCNQ1, HERG, SCN5A).
• This genetic finding contrasts with the clinical diagnosis of LQT1.

Implications:

• The absence of mutations in common LQTS-associated genes highlights the potential for novel genetic variants or alternative etiologies in LQT1.
• Further investigation into less common genes or non-genetic factors may be warranted for this family.
• This case underscores the importance of integrating clinical, ECG, and genetic data for comprehensive LQTS diagnosis and management.