Genetic analysis of mosaic tetrasomy 9p syndrome diagnosed prenatally： A case report and literature review

Background　Mosaic tetrasomy 9p syndrome is a rare chromosomal disorder with high phenotypic heterogeneity. Most cases are accompanied by multiple malformations or developmental delay, while cases with normal phenotypes are rare. Objective　To explore the strategies for prenatal genetic diagnosis, phenotypic heterogeneity, and factors related to prognosis in mosaic 9p tetrasomy syndrome, thereby providing important references for clinical genetic counseling and pregnancy decisionmaking. Methods　A retrospective analysis was performed on the prenatal testing data (non-invasive prenatal testing NIPT, chromosomal microarray analysis CMA of amniotic fluid, chromosomal karyotyping of amniotic fluid cells, fluorescence in situ hybridization FISH of interphase amniotic fluid cells), fetal ultrasound findings, postnatal umbilical cord blood karyotyping data of a 35-year-old pregnant woman (G2P1), and 2-year follow-up data of the pediatric patient. Relevant reports were also reviewed and discussed. Results　The pregnant woman was 35 years old. At 15 weeks of gestation, NIPT indicated a duplication of approximately 39.16 Mb in the 9p24.3 - p13.1 region. At 19 weeks, CMA of amniotic fluid revealed a low-level mosaic duplication of 38.5 Mb in the 9p24.3 - p13.1 region in the fetus. Karyotype analysis of cultured amniotic fluid cells showed no chromosomal abnormalities. At 23 weeks, interphase FISH using 9pter/9qter probes on amniotic fluid cells detected that about 8% of the cells contained four copies of the 9pter probe signal and two copies of the 9qter probe signal. At 33 weeks of gestation, ultrasound showed a left choroid plexus cyst measuring 0.6 cm × 0.5 cm × 0.5 cm. A follow-up ultrasound at 35 weeks revealed no significant structural abnormalities. The patient delivered a phenotypically normal male infant at 38+5 weeks of gestation. Cord blood karyotype analysis showed mosaic 9p tetrasomy with a mosaicism rate of 46%. At a 2-year follow-up, the child remained phenotypically normal, with normal psychomotor development. Conclusion　The prognosis of mosaic tetrasomy 9 syndrome is significantly heterogeneous. Even with a high proportion of abnormal cells in umbilical cord blood (46%), normal phenotypes can still be observed. Comprehensive prenatal evaluation combining NIPT, CMA, FISH, chromosomal karyotyping, and ultrasound examination can reduce the risk of missed diagnosis and misdiagnosis of mosaic tetrasomy 9p syndrome and provide important evidence for clinical genetic counseling and pregnancy management.