Two siblings with early repolarization syndrome: clinical and genetic characterization by whole-exome sequencing

Figures

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  Figure 1. Pedigree and 12-lead electrocardiograms of the two siblings with early repolarization syndrome. (A) The index patient is marked with an arrow. Men are denoted by squares and women by circles. Solid symbols indicate individuals with early repolarization syndrome. Plus symbols next to each individual indicate carrier of the novel ANK3 H2245R variant; minus symbol indicates wild type. (B) Diagnostic inferior early repolarization pattern with high Jp amplitudes of ≥0.35 mV, slurred QRS and horizontal ST-segments in the index patient’s brother. (C) Diagnostic inferolaterlal early repolarization pattern in the index patient with maximal J peak (Jp) amplitudes of 0.20–0.25 mV and slurred QRS in lateral leads.

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  Figure 2. Electrical storm with dynamic early repolarization. Continuous electrocardiographic tracings from the telemetry monitor in the index patient: lead II demonstrates a distinct inferior J-wave with pause-dependent augmentation (red circles) and a monomorphic short-coupled premature ventricular complex triggering polymorphic ventricular tachycardia that rapidly degenerates into ventricular fibrillation. A further increase of the J-wave amplitude (red circles) precedes recurrent ventricular fibrillation. Following each defibrillation there is instantaneous ventricular fibrillation recurrence after four, respectively, two normal beats triggered by the very first monomorphic premature ventricular complex, resulting in three ventricular fibrillation episodes within 30 s. After this last defibrillation, the patient remained in ongoing VF for >1 h due to intractable ventricular fibrillation while being protected by venoarterial extracorporeal membrane oxygenation (VA-ECMO).

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  Figure 3. Termination of electrical storm and suppression of early repolarization. (A) Continuous electrocardiographic tracings from the telemetry monitor in the index patient: prior to the external shock shown isoproterenol was given for 2 min during ongoing ventricular fibrillation. Isoproterenol resulted in successful defibrillation, suppression of the early repolarization pattern (red circle) and of the ventricular fibrillation trigger (note absence of short-coupled premature beats). (B) Synopsis of electrical storm in the index patient: Conventional anti-arrhythmic drugs failed and, by slowing heart rate, retrospectively even increased the number of ventricular fibrillation episodes. Isoproterenol led to sinus tachycardia and suppression of any further ventricular fibrillation episode. VA-ECMO, venoarterial extracorporeal membrane oxygenation.

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  Figure 4. Alignment with ClustalW of the ANK3 protein in the region of the variant p. H2245R. The histidine at this position is conserved in fish, birds, mammals, marsupials and human.