Chromosomal Microarray Analysis for the Fetuses with Aortic Arch Abnormalities and Normal Karyotype

Abstract

Background: Aortic arch abnormalities (AAA) are abnormal embryologic developments of the aorta and its branches. Their outcomes often depend on their association with other congenital diseases and genetic testing results. Objective: This study aimed to evaluate the yield of chromosomal microarray analysis (CMA) in fetuses with different patterns of AAA and normal karyotype. Methods: Data from 158 pregnancies referred for prenatal CMA testing due to fetal AAA were obtained between April 2016 and April 2019. Fetuses with isolated AAA, AAA accompanied by soft ultrasound markers, and AAA with other ultrasound malformations were classified into groups A, B, and C, respectively. Cases with detectable karyotype aberrations were excluded from the study. Results: Twenty cases (12.7%) of submicroscopic anomalies were detected in 158 cases with normal karyotype, comprising 16 cases (10.1%) of clinically significant variants, two cases (1.3%) of variants of unknown significance, and two variants (1.3%) that were likely benign. Microdeletion of 22q11.2 accounted for 25% (4/16) of the clinically significant variants. The overall incremental yields by CMA in group A, group B, and group C were 1.8%, 2.3%, and 24.1%, respectively. Except for double aortic arch, the incremental yield of clinical significant findings for each type of AAA in group C was much higher than that in group A and group B. In group A, a clinically significant variant was only detected in one fetus with right aortic arch (RAA) (1.8%, 1/57). Conclusions: In addition to 22q11.2 microdeletion, many other clinically significant submicroscopic variants are present in fetuses with AAA, especially in fetuses with other ultrasound malformations. Although CMA is always recommended in the presence of any malformation in many countries, our results suggest insufficient evidence to recommend CMA in fetuses with isolated AAA, except for isolated RAA.