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Utility of genetic evaluation in infants with congenital heart defects admitted to the cardiac intensive care unit
Author(s) -
AhrensNicklas Rebecca C.,
Khan Shama,
Garbarini Jennifer,
Woyciechowski Stacy,
D'Alessandro Lisa,
Zackai Elaine H.,
Deardorff Matthew A.,
Goldmuntz Elizabeth
Publication year - 2016
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.37891
Subject(s) - medicine , genetic testing , medical genetics , exome sequencing , etiology , population , pediatrics , neonatal intensive care unit , bioinformatics , genetics , pathology , biology , mutation , environmental health , gene
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.