Use of Clinical Exome Sequencing in Isolated Congenital Heart Disease.

Abstract

A newborn boy was transferred to our hospital with antenatal diagnosis of complex congenital heart disease (CHD) that included hypoplastic left heart syndrome with mitral atresia, aortic stenosis, double-outlet right ventricle, and normally related great arteries. Antenatal screening including maternal integrated prenatal screening and anatomy scan at 19 weeks was normal. Diagnosis was confirmed at a fetal echocardiogram performed at 23-weeks gestation because of a paternal family history of CHD. This included a history of ventricular septal defect and pulmonary stenosis in 33-year-old father who had cardiac surgery at 4 years of age, tetralogy of Fallot in the paternal uncle, and unspecified valve surgery in the paternal grandmother. The 33-year-old mother had a history of uterine fibroids, no history of CHD, and no previous pregnancy losses. The parents were nonconsanguineous. Figure 1 shows the family pedigree. Figure 1. Family pedigree showing affected members (black color). HLHS indicates hypoplastic left heart syndrome; PS, pulmonary stenosis; TOF, tetralogy of Fallot; and VSD, ventricular septal defect. Following delivery at 39+3 weeks, the patient underwent staged palliation including a Norwood procedure at 1 day of age and a superior cavopulmonary connection at 6 months of age. At age 7 months, he had an episode of duskiness during physical therapy at home followed by bradycardia with poor perfusion, which required urgent hospitalization and institution of extracorporeal membrane oxygenation. The baby was transitioned to a right ventricular assist device on day 5 of extracorporeal membrane oxygenation. Unfortunately, on day 10 after device implantation, he had an extensive proximal left middle cerebral artery infarct with significant cortical and white matter loss. Mechanical circulatory support was withdrawn, and the patient passed away. Genetic evaluation was performed during the first hospitalization. No dysmorphic features were identified in the patient or his father, and chromosomal microarray showed a normal 46, XY male …