Abstract
Background: Left ventricular noncompaction (LVNC) is a rare cardiomyopathy, long QT syndrome (LQTS) is a rare ion channel disease, and simultaneous occurrence of both is even rarer. Further clinical reports and studies are needed to identify the association between LVNC and LQTS and the underlying mechanism. Methods and Results: A 26-year-old primigravida was referred at 25 weeks gestation for prenatal echocardiography due to fetal bradycardia detected during the routine ultrasound examination. The echocardiographic findings were consistent with biventricular noncompaction cardiomyopathy (BVNC) with pulmonary stenosis and suspected LQTS. After detailed counseling, the couple decided to terminate the pregnancy, and subsequent postmortem examination confirmed BVNC and pulmonary stenosis. Then, A trio (fetus and the parents) whole-exome sequencing (WES) and copy number variation sequencing (CNV-seq) were performed. CNV-seq identified no aneuploidy or pathogenic CNV. A de novo missense variant in KCNH2 (NM_000238.3:c.1847A > G,p.Tyr616Cys) was identified by WES. This KCNH2 missense mutation was classified as pathogenic according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology variant interpretation guidelines. Conclusion: We report the first prenatal case of KCNH2 mutation presenting with LVNC combined with bradycardia and second-degree 2:1 atrioventricular block. Importantly, this case reminds clinicians to systematically search ion channel gene mutations in patients with LVNC and arrhythmia.