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Heterozygous desmoplakin (DSP) variants presenting with early onset cardiomyopathy and refractory ventricular

Akshay Mathavan1, Urszula Krekora2, Miguel Belaunzaran Dominguez1

  • 1Internal Medicine, University of Florida, Gainesville, Florida, USA.

BMJ Case Reports
|February 21, 2024
PubMed

Insights

Novel desmoplakin gene mutations cause arrhythmogenic cardiomyopathy, leading to early-onset heart dysfunction and severe ventricular arrhythmias. This genetic heart condition proved resistant to standard treatments.

Area of Science:

  • Cardiology
  • Genetics
  • Molecular Biology

Background:

  • Arrhythmogenic cardiomyopathy (ACM) is a non-ischaemic cardiomyopathy characterized by myocardial dysfunction and inherited conduction disease.
  • It predisposes individuals to malignant ventricular arrhythmias and sudden cardiac death.
  • Phenotypic presentation of ACM can be diverse, involving the left, right, or both ventricles.

Observation:

  • A subset of ACM is linked to mutations in desmosomes, crucial for myocardial structural and electrical integrity.
  • Mutations in the desmoplakin (DSP) gene, a key desmosome protein, are implicated in ACM development.
  • This report details a case of desmoplakin ACM due to novel heterozygous DSP mutations (c.1061T>C and c.795G>C).

Findings:

  • The patient presented with early-onset non-ischaemic cardiomyopathy and recurrent ventricular tachycardia.
  • The condition was refractory to multiple therapies, including antiarrhythmics, ablation, sympathectomy, and frequent implantable cardioverter-defibrillator shocks.
  • Novel heterozygous DSP mutations were identified as the underlying cause.

Implications:

  • This case highlights the role of DSP mutations in arrhythmogenic cardiomyopathy.
  • Understanding these genetic underpinnings is crucial for diagnosing and managing ACM.
  • Further research into DSP-related ACM may reveal novel therapeutic targets for refractory cases.

Keywords:
arrhythmiasgeneticsheart failurepacing and electrophysiology

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