International Triadin Knockout Syndrome Registry

Area of Science:

• Cardiology
• Genetics
• Rare Diseases

Background:

• Triadin knockout syndrome (TKOS) is a rare inherited arrhythmia syndrome.
• It is caused by recessive null mutations in the TRDN gene, affecting cardiac triadin.
• Previous studies identified extensive T-wave inversions and exercise-induced cardiac arrest in affected children.

Purpose of the Study:

• To establish and describe the International Triadin Knockout Syndrome Registry.
• To collect and analyze clinical and genetic data from patients with genetically proven TRDN null mutations.
• To better understand the disease spectrum and outcomes of TKOS.

Main Methods:

• Established the International Triadin Knockout Syndrome Registry.
• Collected clinical and genetic data via an online REDCap survey.
• Included patients with genetically confirmed homozygous/compound heterozygous TRDN null mutations.

Main Results:

• The registry includes 21 patients from 16 families.
• 95% of patients experienced cardiac arrest or syncope by age 3.
• T-wave inversions (84%) and QT prolongation (53%) were common; 74% had recurrent cardiac events despite treatment.

Conclusions:

• TKOS is a potentially lethal disease with characteristic ECG findings and early-onset arrhythmias.
• TRDN genetic testing is recommended for unexplained cardiac arrest in children.
• The registry aims to facilitate understanding and future gene therapy trials for TKOS.