Abstract

ABSTRACT Background Dysmorphology evaluation is important for congenital heart disease (CHD) assessment, but there are no prior investigations quantifying the screening performance compared to standardized genetics evaluations. We investigated this through systematic dysmorphology assessment in CHD patients with standardized genetic testing in primarily pediatric patients with CHD. Methods Dysmorphology evaluations preceding genetic testing results allowed us to test for associations between dysmorphic status and genetic diagnoses while adjusting for extracardiac anomalies (ECAs). We use a test‐negative case–control design on a pediatric inpatient CHD cohort for our study. Results Of 568 patients, nearly 96% of patients completed genetic testing, primarily chromosome microarray (CMA) ± exome sequencing‐based genetic testing (493/568, 86.8%). Overall, 115 patients (20.2%) were found to have genetic diagnoses, and dysmorphic patients had doubled risk of genetic diagnoses, after ECA adjustment (OR = 2.10, p = 0.0030). We found that 7.9% (14/178) of ECA−/nondysmorphic patients had genetic diagnoses, which increased to 13.5% (26/192) in the ECA−/dysmorphic patients. Nearly 43% of ECA+/dysmorphic patients had genetic diagnoses (63/147). The positive predictive value of dysmorphic status was only 26.3%, and the negative predictive value of nondysmorphic status was 88.7%. Conclusions Dysmorphology‐based prediction of genetic disorders is limited because of diagnoses found in apparently isolated CHD. Our findings represent one of the only assessments of phenotype‐based screening for genetic disorders in CHD and should inform clinical genetics evaluation practices for pediatric CHD.