Prenatal diagnosis of non-mosaic sex chromosome abnormalities: a 10-year experience from a tertiary referral center.

Objectives: The aim of this study was to explore the frequency and profile of non-mosaic sex chromosome abnormalities detected in prenatal diagnosis over the past 10 years.

Methods: We retrospectively reviewed pregnancies diagnosed with non-mosaic sex chromosome abnormalities between January 2012 and December 2021, using karyotyping and/or single nucleotide polymorphism (SNP) array. Maternal age, indications for testing, and outcomes were recorded.

Results: Traditional karyotyping identified 269 (0.90 %) cases of non-mosaic sex chromosome abnormalities among 29,832 fetuses, including 249 cases of numerical abnormalities, 15 unbalanced structural abnormalities, and 5 balanced structural abnormalities. The overall detection rate of common sex chromosome aneuploidies (SCAs) was 0.81 %, with 47,XXY, 47,XXX, 47,XYY, and 45,X accounting for 0.32 , 0.19, 0.17, and 0.13 % respectively. All showed a fluctuating upward trend over the study period, except for 45,X. During the first five years (2012-2016), the major indication for testing was advanced maternal age (AMA), followed by abnormal ultrasound, abnormal noninvasive prenatal testing (NIPT), and abnormal maternal serum screening (MSS). In the second five years (2017-2021), the most frequent indication was abnormal NIPT, followed by AMA, abnormal ultrasound, and abnormal MSS. Among the 7,780 cases that underwent SNP array in parallel, an additional 29 clinically significant aberrations were detected. The most frequent aberration was a microdeletion in the Xp22.31 region, which was associated with X-linked ichthyosis.

Conclusions: Fetal sex chromosome abnormalities are important findings in prenatal diagnosis. The application of NIPT and SNP array technology has greatly improved the detection of SCAs and submicroscopic aberrations associated with sex chromosomes.