Noncompaction Cardiomyopathy, Sick Sinus Disease, and Aortic Dilatation: Too Much for a Single Diagnosis?

Area of Science:

• Cardiovascular Genetics
• Molecular Cardiology

Background:

• Mutations in the HCN4 gene are established causes of sick sinus syndrome (SSS).
• Recent studies suggest HCN4 mutations may be associated with a broader spectrum of cardiac abnormalities.

Observation:

• This report details three family members presenting with a complex cardiac phenotype.
• The affected individuals carried the pathogenic p.Gly482Arg variant in the HCN4 gene.

Findings:

• The identified HCN4 variant was associated with both sick sinus syndrome and a more complex phenotype.
• This phenotype included left ventricular noncompaction cardiomyopathy and aortic dilatation.

Implications:

• Genetic testing for HCN4 mutations should be considered in patients with unexplained SSS, noncompaction cardiomyopathy, or aortic dilatation.
• Understanding the genotype-phenotype correlation in HCN4 mutations is crucial for accurate diagnosis and management of affected families.