Trans-2,3-enoyl-CoA reductase-like-related catecholaminergic polymorphic ventricular tachycardia in a child: Clinical course and management outcomes

ABSTRACT

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare but potentially fatal inherited arrhythmia. We report a 7-year-old child with CPVT associated with a homozygous trans-2,3-enoyl-CoA reductase-like c.730 + 1G>C variant. To our knowledge, this variant has not been previously reported in the indexed peer-reviewed literature. Prophylactic implantation of an implantable cardioverter defibrillator before symptom onset proved lifesaving during a subsequent ventricular fibrillation episode despite beta-blocker therapy.

CASE REPORT

A 7-year-old child was referred for evaluation because of a family history of sudden cardiac death (SCD). The child’s older brother died at 6 years of age after being found unresponsive in bed. Autopsy reported SCD. The family history is summarized in the pedigree [Figure 1].

Figure 1.

Pedigree of Patient A

Routine laboratory tests were normal. Resting ECG was unremarkable; after brief exertion, QTc was borderline. Exercise treadmill testing reached a peak HR of 146 bpm without ventricular ectopy. Echocardiography showed increased LV trabeculation (NC/C 1:1.5–1.8 in the apical segment); cardiac MRI confirmed trabeculation without meeting diagnostic criteria for LV noncompaction. A 24-h Holter ECG showed moderate QTc prolongation. However, a subsequent 3-day Holter recorded paired polymorphic premature ventricular complexes following sinus tachycardia up to 165 bpm, triggered by emotional stress.

Whole-exome sequencing identified a homozygous splice-site variant in trans-2,3-enoyl-CoA reductase-like (TECRL) (NM_001010874.5): c.730 + 1G>C. In silico prediction (SpliceAI) suggested exon skipping. Both parents were heterozygous carriers [Figure 2].

Figure 2.

Sanger sequencing results showing the nucleotide substitution c.730 + 1G>C in the trans-2,3-enoyl-CoA reductase-like gene in the deoxyribonucleic acid of the patient’s mother (a) and father (b)

TECRL transcripts were not detected in RNA isolated from the whole blood of the proband, the proband’s mother, or a healthy control, suggesting that TECRL expression in peripheral blood leukocytes may be very low.

Given the family history, genotype, and stress-induced polymorphic ventricular ectopy, the patient was diagnosed with TECRL-associated catecholaminergic polymorphic ventricular tachycardia (CPVT). Nadolol was initiated (1.2 mg/kg/day). An implantable cardioverter defibrillator (ICD) was implanted because of the malignant phenotype reported for TECRL-related disease and limited evidence for beta-blocker efficacy in this setting. The ICD was programmed for rapid ventricular fibrillation (VF) detection and shock therapy, balancing timely treatment with minimization of inappropriate therapies.

Five months later, while running, the patient developed syncope during VF. The ICD delivered an appropriate shock, terminating VF [Figure 3].

Figure 3.

Implantable cardioverter defibrillator (ICD) data fragment: ventricular fibrillation successfully terminated by an ICD shock

Left cardiac sympathetic denervation (LCSD) was subsequently performed. No further arrhythmic events have occurred during 3 years of follow-up.

DISCUSSION

Currently, published clinical data on TECRL-associated disease remain limited: approximately 20 patients from 12 families have been reported. Most affected individuals carry biallelic (homozygous or compound heterozygous) variants; however, CPVT-like phenotypes in heterozygous carriers have also been described.[1] Reported presentations overlap features of primary electrical heart disease, most notably long QT syndrome and CPVT, suggesting a recognizable combined phenotype.[2,3]

Here, we describe a patient with a strong family history of SCD who was identified before clinical presentation. The phenotype showed elements of both long QT syndrome and CPVT. Notably, exercise testing remained negative for ventricular ectopy despite maximal effort, which is atypical for classic CPVT. In CPVT, ventricular arrhythmias often appear at heart rates around 110–120 bpm, whereas TECRL-associated disease may have a higher threshold.[4]

Moderate QTc prolongation is reported in most cases.[3,4] Although some values were obtained post-resuscitation, persistent QTc prolongation after adrenergic stimulation (isoproterenol/adrenaline) resembles long QT syndrome patterns.[5]

Echocardiography in our patient revealed increased LV trabeculation, consistent with previous observations in patients with CPVT.[6,7] The coexistence of CPVT and increased LV trabeculation or noncompacted cardiomyopathy is observed in certain RYR2 gene variants, such as R169Q variant.[6] The cellular mechanisms contributing to both structural and electrical abnormalities in these patients are an active area of research. The presence of increased trabeculation in patients with TECRL variants may suggest a role of Ca2+ dysregulation in the pathogenesis of both structural and rhythm abnormalities.[8]

According to the literature, beta-blocker therapy was prescribed to all patients following in-hospital evaluation.[2,3,4,5] Overall efficacy appears limited, with some suggestion of better outcomes on nadolol.[5,9] In our patient, VF occurred despite nadolol, consistent with the literature indicating a persistently high arrhythmic risk on beta-blocker monotherapy in TECRL-associated disease.[10] Verapamil was not used in this patient; given limited TECRL-specific data and standard CPVT management principles, we prioritized a nonselective beta-blocker.

LCSD may represent a useful adjunct, given its established efficacy in CPVT and certain types of long QT syndrome.[11] In our case, no arrhythmic events occurred over 3 years after LCSD. Nevertheless, in the absence of robust long-term data in TECRL-associated disease, ICD implantation remains central for SCD prevention, particularly when pharmacotherapy alone may be insufficient.

This case highlights the significant arrhythmogenic risk associated with TECRL gene variants in CPVT, underscoring the limited efficacy of beta-blocker therapy and the critical role of ICD implantation for preventing life-threatening events, even in asymptomatic patients. These findings emphasize the need for vigilant management and further research into optimal treatment strategies for patients with TECRL gene variants.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.