Non-Invasive Screening Test Paradox in a Case Born with Mixed Gonadal Dysgenesis (45,X/46,Xy)

Noninvasive prenatal testing (NIPT) is commonly used to screen for fetal trisomy 13, 18, and 21 and often for sex chromosomal aneuploidies (SCAs). Although the testing is also used for sex chromosomal aneuploidies, it is not as efficient as it is for common trisomies. In this particular study, we present a case for whom the NIPT diagnosis was originally 45,X and who was diagnosed with mixed gonadal dysgenesis 45,X/46,XY after birth. A 38-year-old [G3P3] pregnant woman underwent NIPT at 15 weeks’ gestation and was found to be at probable risk for 45,X. Because cordocentesis is an invasive procedure, the pregnant woman did not want to undergo cordocentesis. Consequently, postnatal cytogenetic analysis was performed and the baby’s karyotype was shown to be 45,X/46,X,+mar?. No numerical and/or structural anomalies were observed in the karyotypes of parents and siblings. Based on the microarray analysis of the analyzed sample, one copy of the X chromosome was detected in all cells and the presence of one copy of the Y chromosome was detected in a ~40% mosaic state: arr(X) x1,(Y)x1[0.4]. SRY gene duplication on Y chromosome was confirmed by fluorescence in situ hybridization (FISH) and microarray analysis. The patient’s clinical examination showed ambiguous genitalia (clitoromegaly) and dysmorphic facial features. The baby underwent surgery for aortic coarctation. The results were consistent with a genetic diagnosis of 45,X/46,XY mixed gonadal dysgenesis. Genetic counselling was offered to the family. In conclusion, NIPT still has potential limitations in correctly identifying sex chromosomes and mosaicism that may mislead clinicians and families.