Description:
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<jats:bold>Introduction:</jats:bold>
Arrhythmogenic cardiomyopathy (ACM) resulting from variants in the desmosomal gene desmoplakin (DSP) is typically an adult onset disorder. Here, we describe penetrance, expression and outcomes of DSP-associated ACM in children.
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<jats:bold>Methods:</jats:bold>
Patients aged ≤21 years with pathogenic/likely pathogenic variants in DSP were included. Penetrance was defined by:(i) ECG: T-wave inversion V4-V6; mean QRS amplitude <0.5mV in limb leads.(ii) Arrhythmia: >500 VPBs/24 hours, non-sustained or sustained ventricular arrhythmia (VA)(iii) LV dysfunction (EF<50%)(iv) Sub-epicardial late gadolinium enhancement (LGE). The cardiac phenotype was defined as primarily RV, isolated LV (left dominant) or biventricular. Myocardial inflammation was defined as chest pain with elevated troponin ± ST segment changes. A composite primary outcome was sustained VA, death or transplant.
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<jats:bold>Results:</jats:bold>
We identified 24 patients (67% female) inclusive of 8 probands and 16 family members. Variants were truncating in 22 and missense in 2; a second variant occurred in 4. Presenting symptoms were cardiac arrest (1); myocardial inflammation (3) with cardiac arrest (1), sustained VA (1), dyspnea (2), syncope (1), palpitations (1).
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<jats:p>ACM was penetrant in 17 (71%), with expression first evident at 15.2±3.3 years. The cardiac phenotype was left dominant (12) and biventricular (5). Isolated RV disease was not seen. Penetrant features were:(i) ECG: transient T-wave inversion in 1 (6%) and QRS amplitude <0.5mV in 6 (35%). (ii) Arrhythmia in 14 (82%) evident at presentation in 13 (92%) and an isolated finding in 2. (iii) LV dysfunction in 10 (59%; EF 35 ± 12%) evident at presentation in 9. (iv) Sub-epicardial LGE in 13 (76%) evident at presentation in 12 (92%) and an isolated finding in 2. Over 3.4±3.2 years, 6 (35%; 4 probands and 2 family members) reached the primary outcome; sustained VA at presentation (3), sustained VA (2), transplant (1). Myocardial inflammation occurred in 5 (21%), 2 of whom reached the primary outcome but this was not significant (p=0.79).</jats:p>
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<jats:bold>Conclusions:</jats:bold>
DSP-mediated ACM may be fully penetrant in children affecting both probands and family members. VA and subepicardial LGE are prominent early features of disease and pediatric surveillance should reflect these findings.
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