Utility of Genetic Evaluation in Infants with Congenital Heart Defects Admitted to the Cardiac Intensive Care Unit

被引:32
作者
Ahrens-Nicklas, Rebecca C. [1 ]
Khan, Shama [2 ]
Garbarini, Jennifer [3 ]
Woyciechowski, Stacy [1 ]
D'Alessandro, Lisa [4 ]
Zackai, Elaine H. [1 ]
Deardorff, Matthew A. [1 ]
Goldmuntz, Elizabeth [5 ]
机构
[1] Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA
[2] Rutgers Robert Wood Johnson Med Sch, Div Maternal Fetal Med, New Brunswick, NJ USA
[3] Recombine LLC, Philadelphia, PA USA
[4] Texas Childrens Hosp, Div Pediat Cardiol, Houston, TX 77030 USA
[5] Childrens Hosp Philadelphia, Div Cardiol, 34th St & Civ Ctr Blvd, Philadelphia, PA 19104 USA
关键词
congenital heart defects; genetic testing; cardiac intensive care; clinical genetics; genome wide array; GREAT-ARTERIES; DISEASE; MUTATIONS; TRANSPOSITION;
D O I
10.1002/ajmg.a.37891
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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. Agenetic 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. (C) 2016 Wiley Periodicals, Inc.
引用
收藏
页码:3090 / 3097
页数:8
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