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BackgroundCongenital heart disease (CHD) can occur as part of a genetic syndrome or as an isolated defect and genetic factors contribute to a majority of cases. Early diagnosis of syndromic CHD improves outcome but can be clinically challenging in the first year of life. Chromosome microarray analysis can identify causes of both syndromic and isolated CHD. The objectives of this study were to determine the diagnostic yield for chromosome microarray analysis and compare genetic testing practices among infants with CHD.Methods and ResultsA retrospective chart review was performed for infants with CHD identified by echocardiogram. CHD was classified using the National Birth Defects Prevention Study system, which takes intoaccount complexity, CHD type, and extracardiac phenotype. Of 1087 infants with CHD, 277(25%) had karyotype, FISH and/ or chromosome microarray analysis. Of the 121 patients (11%)who had chromosome microarray analysis, genetic abnormalities were identified in 35 (29%)infants, including 16 isolated CHD and 19 non isolated CHD. Striking was the number of infants that received no genetic testing, and the inconsistent genetic testing practices. Infants with CHD do not receive consistent genetic testing, even though abnormalities were identified ininfants with a variety of phenotypes.ConclusionsThe majority of infants with CHD do not undergo genetic testing, and only a small proportionreceives chromosome microarray analysis. The frequency of abnormal chromosome microarrayanalysis results did not differ by CHD complexity or the presence of extracardiac malformations, suggesting chromosome microarray analysis is warranted for first-line testing for infants withCHD. Chromosome microarray abnormalities of unknown significance present opportunities to identify novel causes of CHD and define disease etiology. Given the likelihood of an uncertain result, expertise is required for clinical interpretation and genetic counseling.