Characterization of cardiac involvement in children with LMNA-related muscular dystrophy

Figures

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  FIGURE 1. (A): Timeline of major and minor events in pediatric patients with lamin-related muscular dystrophy defined on the basis of age. Atrial arrhythmias, asystole/atrial standstill, and malignant arrhythmias preceded structural and cardiac functional abnormalities (DCM criteria or depressed LVEF). Median time values are represented by vertical grey line when required. DCM and LVEF are represented by a dot. Pacemaker are represented by a star. Arrhythmias and ICD are represented by an inverted triangle. Gait loss and NIMV are represented by a square, and death are represented by a cross. When required, minimum to maximum range age is represented in grey box and whiskers. Abbreviations: LVEF, left ventricular ejection fraction. (B): Timeline of major and minor events in pediatric patients with lamin-related muscular dystrophy defined on the basis of enrollment (time 0 is the time of enrollment represented by a vertical blue dotted line). Median time values are represented by a vertical grey line. DCM and LVEF are represented by a dot, pacemaker is represented by a star, arrhythmias and ICD are represented by an inverted triangle and death is represented by a cross. Abbreviations: LVEF,…

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  FIGURE 2. (A): comparison of values at enrollment and at last follow-up; LVEF values (%). Patients are represented as black dots at enrollment, and triangles represent patients at last follow-up. Red triangles show patients requiring an ICD (gray device represented in the graphic). Cardiomyopathy is represented by a heart. Black lines link the same patient in the two different moments of follow-up. (B): comparison of values at enrollment and at last follow-up; four-chamber GLS values (%). Patients are represented as black dots at enrollment and triangles at last follow-up. Red triangles show patients requiring an ICD (gray device represented in the graphic). Cardiomyopathy is represented by a heart. Black lines link the same patient in the two different moments of follow-up.

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  FIGURE 3. (A) Four-chamber GLS values (%) compared with LVEF values (%) for each patient at enrollment. At enrollment, despite normal LVEF (>55%), values below 20.6% are detected (20.6% is the mean normal value published in children). These LVEF values show a decreasing trend at last follow-up (B).

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  FIGURE 4. Three ECG traces from the ILR. (A) Atrial fibrillation (blue arrows) and a ventricular extrasystole (red arrow). (B) Ventricular tachycardia, VF, and asystole from a pediatric patient diagnosed with EDMD. (C) Sinus pause and asystole in a 3-year-old patient.

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  FIGURE 5. Phenotype–genotype graphic correlation. A schematic representation of the LMNA gene is shown. Top, major cardiac events, followed by rare pathogenic/likely pathogenic LMNA variants identified in our patients with the corresponding amino acid or nucleotide changes. Bottom, structural protein: the coil 1A–1B and coil 2A–2B constituting the ⍺-helical rod domain. Abbreviations: DCM, dilated cardiomyopathy; ICD, implantable cardioverter defibrillator; PM, pacemaker; NLS, nuclear location signal; Ig, immunoglobulin.