INVESTIGATION OF CHROMOSOMAL AND SUBCHROMOSOMAL ABNORMALITIES IN FETUSES WITH CONGENITAL HEART DEFECTS
Main Article Content
Abstract
Objective: To describe chromosomal and submicroscopic abnormalities in fetuses with congenital heart defects (CHDs) or high-risk cardiac ultrasound markers detected at Hanoi Medical University Hospital.
Methods: A cross-sectional study was conducted on 60 pregnant women whose fetuses were diagnosed with CHDs or clinically significant cardiac ultrasound markers. All cases underwent amniocentesis followed by genetic analysis using both karyotype and copy number variation sequencing (CNVseq) at Hanoi Medical University Hospital from 2022 to 2024. Fetuses were classified according to specific types of cardiac anomalies.
Results: The mean maternal age was 31.3 ± 5.9 years and mean gestational age at diagnosis was 19 weeks 3 days. Common cardiac findings included ventricular septal defect (18.3%), tetralogy of Fallot (13.3%), conotruncal defects (10.0%), aortic arch anomalies (8.3%), left ventricular outflow tract obstruction (5.0%), and high-risk echogenic intracardiac focus (25.0%). The combined detection rate was 48.3% (29/60). Karyotype identified abnormalities in 38.3% of cases, including two balanced translocations and one marker chromosome undetectable by CNVseq. CNVseq detected 43.3% and identified six additional pathogenic copy number variants (10.0%) missed by karyotype. The highest detection rate was in the high-risk EIF group (80.0%), with 22q11.21 deletion being the most common pathogenic CNV.
Conclusion: Congenital heart defects are strongly associated with genetic abnormalities. Conotruncal and great vessel anomalies are primarily linked to subchromosomal abnormalities detectable by CNVseq, while karyotype remains essential for identifying balanced rearrangements and marker chromosomes. Combined use of both methods maximizes prenatal genetic diagnostic yield in fetuses with cardiac abnormalities.
Keywords
Chromosomal abnormalities, subchromosomal abnormalities, congenital heart defects, prenatal diagnosis, CNVseq, karyotype
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References
2. Liu Y, Chen S, Zühlke L, et al. Global birth prevalence of congenital heart defects 1970–2017: updated systematic review and meta-analysis of 260 studies. International Journal of Epidemiology. 2019;48(2):455-463.
3. Pierpont ME, Brueckner M, Chung WK, et al. Genetic basis for congenital heart disease: revisited. A scientific statement from the American Heart Association. Circulation. 2018;138(21):e653-e711.
4. Wapner RJ, Martin CL, Levy B, et al. Chromosomal microarray versus karyotyping for prenatal diagnosis.
5. New England Journal of Medicine. 2012; 367(23): 2175-2184.
6. Wang Y, Cao L, Liang D, et al. Prenatal chromosomal microarray analysis in fetuses with congenital heart disease: a prospective cohort study. American Journal of Obstetrics and Gynecology. 2018;218(2):244.e1-244.e17.
7. Hillman SC, McMullan DJ, Hall G, et al. Use of prenatal chromosomal microarray: prospective cohort study and systematic review and meta-analysis. Ultrasound in Obstetrics & Gynecology. 2013;41(6):610-620.
8. Bùi Hải Nam, Trần Danh Cường và cộng sự. Bất thường nhiễm sắc thể ở thai nhi có dị tật tim mạch phát hiện trên siêu âm. Tạp chí Phụ sản. 2018;16(1):52-57.
9. Trương Thanh Vị, Đỗ Thị Mỹ Khanh, Cao Hữu Thịnh và cộng sự. Khảo sát bất thường di truyền bằng các kỹ thuật chẩn đoán trước sinh trên thai nhi mắc tim bẩm sinh tại Bệnh viện Từ Dũ. Tạp chí Y học Việt Nam. 2023;529(1):278-283.
10. Society for Maternal-Fetal Medicine (SMFM); Prabhu M, Kuller JA, Biggio JR. SMFM Consult Series #57: Evaluation and management of isolated soft ultrasound markers for aneuploidy in the second trimester. American Journal of Obstetrics and Gynecology. 2021;225(4):B2-B15.
11. American College of Obstetricians and Gynecologists Committee on Genetics. Committee Opinion No. 581: The use of chromosomal microarray analysis in prenatal diagnosis. Obstetrics & Gynecology. 2013;122(6):1374-1377.