Partial atrioventricular canal defect and aortic coarctation associated with variants in GDF1 and NOTCH1 genes: A case report

Background: A peculiar subgroup of patients with partial or complete atrioventricular canal defect exhibits a spectrum of left-sided obstructions including right ventricular dominance and aortic coarctation. The association of atrioventricular canal defect with left-sided obstructions is found in several genetic syndromes; however, the molecular basis of nonsyndromic atrioventricular canal defect with aortic coarctation is still poorly understood. Although some candidate genes for nonsyndromic atrioventricular canal defect are known, a complex oligogenic inheritance determined in some cases by the co-occurrence of multiple variants has also been hypothesized.

Case report: We describe a nonsyndromic infant with mesocardia with viscero-atrial situs solitus, partial atrioventricular canal defect, mild right ventricular dominance, and coarctation of the aorta. Next generation sequencing genetic testing revealed variants in two genes, GDF1 and NOTCH1, previously reported in association with atrioventricular canal defect and left-sided obstructive lesions, respectively.

Conclusion: The present report could support the hypothesis that the co-occurrence of cumulative variants may be considered as genetic predisposing risk factor for specific congenital heart defects.