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Cadherin 2-Related Arrhythmogenic Cardiomyopathy: Prevalence and Clinical Features
Alice Ghidoni1, Perry M Elliott2, Petros Syrris2
1Center for Cardiac Arrhythmias of Genetic Origin (A.G., M.-C.K., P.J.S., L.C.), Istituto Auxologico Italiano, IRCCS, Milan, Italy.
Circulation. Genomic and Precision Medicine
|February 10, 2021
Summary
Arrhythmogenic cardiomyopathy (ACM) can be caused by pathogenic variants in the nondesmosomal CDH2 gene. This study found CDH2 variants in 1.2% of ACM patients, who predominantly experienced ventricular arrhythmias rather than heart failure.
Area of Science:
- Cardiovascular Genetics
- Inherited Cardiac Diseases
- Molecular Cardiology
Background:
- Arrhythmogenic cardiomyopathy (ACM) is an inherited heart condition characterized by fibrofatty ventricular replacement.
- Desmosomal gene variants explain up to 60% of ACM cases.
- The role of nondesmosomal genes, like CDH2, in ACM is increasingly recognized.
Purpose of the Study:
- To determine the prevalence of pathogenic variants in the CDH2 gene in patients diagnosed with ACM.
- To characterize the clinical features and outcomes of ACM patients with CDH2 variants.
Main Methods:
- Genetic screening of CDH2 in 500 unrelated ACM patients negative for variants in known ACM genes.
- Next-generation or Sanger sequencing for CDH2 variant identification.
- Clinical evaluation and cascade screening in families of CDH2-positive probands.
Main Results:
- Pathogenic or likely pathogenic CDH2 variants were identified in 1.2% (6/500) of the studied ACM cohort.
- A total of 24 individuals (9 probands and 15 family members) with CDH2 variants were analyzed.
- Ventricular arrhythmias occurred in 83% of CDH2-positive subjects, while heart failure was rare (8.3%).
Conclusions:
- CDH2 pathogenic variants represent a significant, previously under-recognized genetic cause of ACM.
- ACM associated with CDH2 variants presents with a high burden of ventricular arrhythmias.
- Heart failure is an uncommon clinical manifestation in CDH2-related ACM.
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