Cytoband (10q21.3 human CTNNA3) & (mouse 10qB4 Ctnna3).
Here I present: “Arrhythmogenic Right Ventricular Dysplasia-13“, Victor McKusick, Mendelian Inheritance in Man’, 1966. 致心律不整性右室發育不良。icd10=I42.8
INTRODUCTION.
Arrhythmogenic right ventricular dysplasia (ARVD) is characterized by progressive fibrofatty myocardial replacement, primarily of the right ventricle. The main clinical features are structural and functional abnormalities of the ventricles, electrocardiographic depolarization/repolarization changes, reentrant arrhythmias, and sudden death.
Arrhythmogenic right ventricular dysplasia (ARVD) is an inherited cardiomyopathy in which the muscle of the right ventricle (RV) is gradually replaced by fibrofatty tissue, creating areas of electrical instability that can trigger ventricular arrhythmias and sudden cardiac arrest, especially in young athletes.
Pathophysiology.
Progressive loss of right ventricular cardiomyocytes.
Replacement by fatty and fibrous tissue, particularly in the “triangle of dysplasia”:
RV inflow tract,
RV outflow tract (RVOT),
RV apex
Caused primarily by mutations in desmosomal proteins that anchor cardiac cells together:
PKP2 (plakophilin-2)
DSP (desmoplakin)
DSG2 (desmoglein)
JUP (plakoglobin)
Mechanical stress (such as athletic training) accelerates cell detachment and death.
Clinical Features.
Symptoms:
Palpitations
Syncope (especially exercise-induced)
Exertional dizziness
Sustained or non-sustained ventricular tachycardia
Sudden cardiac arrest
Signs.
T-wave inversions in V1–V3
Epsilon waves (late potentials at the end of QRS; specific but not always present)
PVCs with left bundle branch block (LBBB) morphology, reflecting RV origin
Diagnosis.
1. Imaging
Cardiac MRI: gold standard
RV dilation
Regional wall motion abnormalities
Fatty infiltration or fibrosis
Echocardiography
RV angiography (less common now)
2. Electrocardiography
Epsilon waves
T-wave inversion V1–V3
Ventricular tachycardia with LBBB morphology
3. Genetic Testing
Pathogenic variants in desmosomal genes support the diagnosis.
4. Electrophysiology
Signal-averaged ECG showing late potentials
EP study.
Genetics & Inheritance.
Usually autosomal dominant with variable penetrance.
Family screening is recommended for first-degree relatives.
There is evidence that arrhythmogenic right ventricular dysplasia-13 (ARVD13) is caused by heterozygous mutation in the alpha-T catenin (CTNNA3) gene encoded on cytoband 10q21.3 and genomic coordinate 10:65,912,423 in humans.
Alpha-T catenin (CTNNA3) is a cell adhesion molecule. In intercalated discs of the heart, CTNNA3 is a component of a unique hybrid adhering junction, or area composita, that contains proteins associated with both desmosomes and adherens junctions.
