Severe cardiac conduction disease associated with titin gene mutation

Area of Science:

• Pediatric Cardiology
• Clinical Genetics
• Molecular Cardiology

Background:

• Heart block is a rare pediatric condition with diverse etiologies.
• The genetic basis of heart block in children is not fully understood.
• Titin (TTN) mutations are known causes of various cardiac conditions, but not previously linked to pediatric heart block.

Observation:

• A 9-year-old female with leukodystrophy and a family history of atrial fibrillation presented with syncope.
• The patient exhibited significant conduction abnormalities, including complete heart block (CHB).
• She required pacemaker implantation due to the severity of her cardiac condition.

Findings:

• Genetic testing revealed a pathogenic mutation in the TTN gene.
• This TTN mutation is strongly suspected to be the cause of the patient's cardiac conduction disease.
• This represents the first reported association between pathogenic TTN mutations and pediatric CHB.

Implications:

• This case suggests a potential genetic link between TTN mutations and conduction system disease in children.
• Broadening genetic testing to include TTN mutations may be beneficial for pediatric patients with heart block, especially those with a family history.
• Further research is warranted to confirm the association and elucidate the mechanism by which TTN mutations cause CHB.