Utility of genetic evaluation in infants with congenital heart defects admitted to the cardiac intensive care unit.

Congenital heart defects (CHDs) are heterogeneous and present with a spectrum of severity, with roughly 25% of patients requiring intervention before age 1. The etiology of disease is unknown in many individuals; however, there is a rapidly expanding understanding of genetic risk factors that may contribute to pathogenesis. Through this work, we sought to evaluate the diagnostic yield of a clinical genetics evaluation and associated genetic testing among infants with critical CHDs. Furthermore, we aimed to both determine the utility of microarray and establish a strong baseline that can be used in future studies of the impact of exome sequencing in this population. We completed a retrospective chart review of 364 infants with CHDs admitted to the Cardiac Intensive Care Unit who underwent a clinical genetics evaluation. A genetic diagnosis was established in 25% of patients: 9% of infants were diagnosed prenatally, while 16% were diagnosed postnatally. Cardiac lesion subtype greatly influenced the diagnostic yield. On physical exam, the presence of dysmorphic features, as assessed by a clinical geneticist, was associated with a sevenfold increased likelihood of reaching a diagnosis. Directed by clinical acumen, diagnostic rates varied by testing modality with rates of 23% for karyotype, 12% for fluorescent in situ hybridization or multiplex-dependent ligation probe analysis, 9% for genome wide microarray, and 17% for targeted gene sequencing. Careful consideration of lesion subtype and physical exam findings clarify populations of infants with CHD that benefit from a genetics evaluation and inform an efficient testing paradigm.