Introduction
Prenatal cell-free DNA (cfDNA) screening is commonly used to assess the risk of chromosome abnormalities in a fetus. Although not designed to detect maternal genetic conditions, it can incidentally identify both constitutional and somatic maternal abnormalities. Here, we present a clinical case in which a 33.8Mb Xq deletion was identified in the mother secondary to prenatal testing of her fetus.

Case Presentation
A 24-year-old G1P0000 woman with no significant personal or family medical history underwent prenatal cfDNA screening, which indicated a high risk for an X chromosome abnormality with segmental loss. Ultrasound evaluation performed at 13w3d of gestation showed normal fetal development. On the same day, chorionic villus sampling (CVS) was performed. Aneuploidy FISH screening showed normal signal patterns for chromosomes 13, 18, 21, X, and Y. Chromosomal microarray (CMA) on the same specimen was suggestive of a low-level (<5%) mosaic deletion of a large portion of Xq. Due to the low level of this deletion, we were unable to determine exact breakpoints; however, the deletion appeared to be at least 20 Mb in size. Given that cells with large Xq deletions are not viable (and thus usually lethal in males) and that maternal cell contamination was noted during CMA analysis, we suspected this abnormality of maternal origin.

 

Diagnostic Workup
Subsequent maternal chromosome and CMA analysis confirmed a 33.8 Mb Xq deletion [46,X,del(X)(q21q23).arr[GRCh37] Xq21.1q23(77986149_111789348)x1]. This deleted interval includes at least 96 OMIM genes, many of which are associated with X-linked disorders.  Females with large Xq deletions, such as this one, are generally unaffected due to preferential inactivation of the abnormal X chromosome; however, some female carriers may exhibit features associated with these conditions. Additionally, the identification of this Xq deletion has important reproductive implications. Large Xq deletions with proximal breakpoints from Xq21.1 to Xq25 are associated with a risk of premature ovarian failure. Additionally, this mother carries a 50% risk of passing on the deletion in each pregnancy. Female offspring would be likely asymptomatic, assuming favorable X-inactivation, while male offspring would be affected or non-viable. Of note, all subsequent ultrasound evaluations showed normal fetal development. A baby boy was born at 30w0d with no major health concerns.

Conclusion
This case highlights that prenatal screening and testing can incidentally identify clinically significant maternal conditions. These findings have implications not only for informed reproductive decisions but may also directly affect parental health management and prompt genetic testing for other at-risk relatives. Additionally, this case underscores the importance of carefully interpreting prenatal mosaic results within the context of biological mechanisms, in conjugation with diagnostic testing, ultrasound findings, and other clinical data.