Objective: To investigate the frequency of genetic diagnoses among infants with critical congenital heart disease (CHD) using a comprehensive cardiovascular genetics approach and to identify genotype-phenotype correlations.
Study design: A retrospective chart review of patients evaluated by cardiovascular genetics in a pediatric cardiac intensive care unit from 2010 to 2015 was performed. Infants with CHD who were <1 month of age were included. CHD was classified using structured phenotype definitions. Cardiac and non-cardiac phenotypes were tested for associations with abnormal genetic testing using chi-squared and Fisher exact tests.
Results: Genetic evaluation was completed in 293 infants with CHD, of whom 213 had isolated CHD (iCHD) and 80 had multiple congenital anomalies (MCA). Overall the yield of abnormal genetic testing was 26%. The MCA cohort had a greater yield of genetic testing (39%) than the iCHD cohort (20%) (odds ratio 2.7). Utilizing a non-hierarchical CHD classification and excluding 22q11.2 deletion and common aneuploidies, right ventricular obstructive defects were associated with abnormal genetic testing (P = .0005). Extracardiac features associated with abnormal genetic testing included ear, nose and throat (p=0.003) and brain (p=0.0001) abnormalities. A diagnosis of small for gestational age or intrauterine growth retardation was also associated with abnormal genetic testing (p=0.0061), as was presence of dysmorphic features (p=0.0033, odds ratio 3.5). Nondysmorphic infants with iCHD or MCA had similar frequencies of abnormal genetic testing.
Conclusion: The present study provides evidence to support a comprehensive cardiovascular genetics approach in evaluating infants with critical CHD while also identifying important genotype-phenotype considerations.