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. © 2016 Wiley Periodicals, Inc.
Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Rebecca C
RC
Ahrens-Nicklas
Division of Maternal Fetal Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey.
Shama
S
Khan
Recombine, LLC, Philadelphia, Pennsylvania.
Jennifer
J
Garbarini
Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Stacy
S
Woyciechowski
Division of Pediatric Cardiology, Texas Children's Hospital, Houston, Texas.
Lisa
L
D'Alessandro
Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Elaine H
EH
Zackai
Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Matthew A
MA
Deardorff
Division of Cardiology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Elizabeth
E
Goldmuntz
D059472:Exome / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D006330:Heart Defects, Congenital / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007362:Intensive Care Units; D008297:Male; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D012307:Risk Factors
cardiac intensive care; clinical genetics; congenital heart defects; genetic testing; genome wide array