Co-Phenotype of Left Ventricular Non-Compaction Cardiomyopathy and Atypical Catecholaminergic Polymorphic Ventricular Tachycardia in Association With R169Q, a Ryanodine Receptor Type 2 Missense Mutation.
2020
BACKGROUND: Left ventricular non-compaction (LVNC) is a cardiomyopathy characterized by prominent trabeculae and intertrabecular recesses. We present the cases of 3 girls with the sameryanodine receptor type 2(RYR2) mutation who had phenotypes of both catecholaminergic polymorphic ventricular tachycardia (CPVT) and LVNC .Methods and Results:Clinical characteristics and genetic background of the 3 patients were analyzed retrospectively. Age at onset was 5, 6, and 7 years, respectively. Clinical presentation included syncope during exercise in all 3 patients and cardiac arrest in 2 patients. LVNC diagnosis was confirmed on echocardiography according to previously defined criteria. Exercise stress testing provoked ventricular arrhythmia in two of the patients. Beta-blockers (n=3) and flecainide (n=2) were given, and an implantable cardioverter defibrillator was used in 1 patient. Genotyping identified the sameRYR2-R169Q missense mutation and no other CPVT- or LVNC-related gene mutations. Functional analysis of the mutation using HEK293 cells with single-cell Ca(2+)imaging and [(3)H]ryanodine binding analysis, indicated a gain of function: a reduced threshold for overload-induced Ca(2+)release from the sarcoplasmic reticulum and increased fractional Ca(2+)release. CONCLUSIONS: The rare association of LVNC and CPVT phenotypes withRYR2mutations is less likely to be coincidental. Screening for life-threatening arrhythmias using exercise or pharmacologic stress tests is recommended in LVNC patients to prevent sudden cardiac death in those with preserved LV function.
Keywords:
- Ryanodine receptor
- Phenotype
- Missense mutation
- Internal medicine
- Sudden cardiac death
- Diabetes mellitus
- Catecholaminergic polymorphic ventricular tachycardia
- Medicine
- Left Ventricular Non-Compaction Cardiomyopathy
- Cardiology
- Exercise-induced syncope
- Flecainide
- Implantable cardioverter-defibrillator
- Ryanodine receptor 2
- Cardiomyopathy
- gene mutation
- Correction
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