Pathologic whole exome sequencing analysis in fetuses with minor sonographic abnormal findings and normal chromosomal microarray analysis: case series

Background: No current data exists regarding the occurrence of pathological results when using Whole Exome Sequencing (WES) analysis in a subgroup of fetuses with minor abnormalities and normal Chromosomal Microarray Analysis (CMA) results. Objective: Our study aimed to report our experience with in-utero WES abnormal results, found in fetuses with minor anomalies after a normal CMA result. Methods: A retrospective study conducted in a single tertiary center, during four years, included collating data regarding fetuses with minor structural abnormalities, normal CMA results, and abnormal triple WES test results. Results: Eleven fetuses were included in the study. Eight were with cardiovascular and lymphatic drainage alterations. Two fetuses developed late third-trimester macrocephaly (head circumference ≥ +2 standard deviations), and one fetus had unilateral mildly short and bowed femur bone. In seven cases (63.6%) the parents opted to terminate the pregnancy as a result of the WES analysis results. Conclusion: Our case series raises the possibility that fetuses with even minor structural alterations and normal CMA results can have genetic variants revealable only by WES analysis which can provide critical information regarding pregnancy management.