Genetic testing practices in infants with congenital heart disease

Clinical genetic testing is expanding rapidly, but the application of new testing has not been reported in an unselected, comprehensive congenital heart disease (CHD) patient population. This study aims to identify cytogenetic testing practices and diagnostic yield in infants with CHD as an important first step toward understanding clinical utility of dedicated cytogenetic testing. We hypothesized that chromosome microarray analysis (CMA) would identify genetic abnormalities underlying both syndromic and isolated CHD.

This is a single institution retrospective study that characterizes cytogenetic testing practices and diagnostic yield for all cytogenetic testing in each infant identified with CHD over a 32-month period. CHD was classified by type, complexity, and presence or absence of extracardiac anomalies.

Among the 1087 infants identified with CHD by echocardiogram, 277 infants (25%) had some form of cytogenetic testing, including karyotype, fluorescence in situ hybridization, and/or CMA. Forty-one percent of infants who had cytogenetic testing had more than one test. CMA was performed in 121 patients (11%), and abnormalities (both clinically significant and variants of unknown significance) were identified in 35/121 (29%). Forty-nine percent of CMA abnormalities were in patients with apparently isolated nonsyndromic CHD.

This single institution study identified that only 25% of infants with CHD underwent cytogenetic testing, indicating possible underutilization of testing in this age group. The high multiple testing rate indicates a need for improved guidelines for cost effective testing approaches. The diagnostic yield in this study suggests that CMA is a particularly useful first screening test when a specific syndrome is not clinically identifiable. Larger studies investigating cardiac lesion-specific diagnostic yield in isolated CHD are warranted.