Prenatal diagnosis, genetic analysis, and pregnancy outcomes of fetuses with mosaic isodicentric Y chromosomes

Abstract Background Isodicentric Y chromosomes [idic(Y)] are frequently detected in patients with disorders of sex development (DSDs). However, prenatal cases are rarely reported. We performed comprehensive prenatal diagnostic evaluations in three fetuses with mosaic idic(Y) and followed up on pregnancy outcomes to explore the genotype-phenotype correlation. Methods Amniotic fluid cells from three fetuses were subjected to karyotyping and chromosomal microarray analysis (CMA), with confirmation by fluorescence in situ hybridization (FISH) and real-time quantitative PCR (qPCR). Subsequently, parental karyotypes were analyzed using peripheral blood samples to assess inheritance (de novo vs. inherited). Results All three fetuses exhibited mosaic 45,X with idic(Y) karyotypes, which exhibited distinct breakpoints (Yp11.32, Yq11.221, and Yq11.223). Two fetuses had additional 46,XY cell lines. The SRY gene was retained in all cases. In Fetus 1, the AZF region was intact, whereas in Fetus 2 and Fetus 3, AZFb + c and AZFc were deleted. Fetus 1 was born alive following genetic counseling. Notably, a right adrenal neuroblastoma was detected during late gestation and successfully resected postnatally. The other two pregnant women elected for pregnancy termination. Conclusion The integration of multiple technologies is essential for accurate prenatal diagnosis in cases of mosaic idic(Y). Our findings, including the rare association with neuroblastoma, contribute new insights into the phenotypic spectrum of this condition. Long-term follow-up and multidisciplinary clinical management are crucial for optimizing outcomes in live-born patients.