[Application of chromosomal microarray analysis for fetuses with ventricular septal defects]

Area of Science:

• Medical Genetics
• Fetal Medicine
• Cardiology

Background:

• Ventricular septal defects (VSD) are common congenital heart anomalies.
• Identifying the genetic underpinnings of VSD is crucial for diagnosis and management.
• Previous genetic analyses may not have detected submicroscopic chromosomal imbalances.

Purpose of the Study:

• To investigate the genetic etiology of fetal VSD using chromosomal microarray analysis (CMA).
• To determine the diagnostic yield of CMA in fetuses with VSD, particularly those with normal karyotypes.
• To identify candidate genes associated with VSD.

Main Methods:

• A cohort of 248 fetuses with VSD was analyzed.
• Standard karyotyping was performed on all fetuses.
• Chromosomal microarray analysis (CMA) was applied to selected fetuses, including those with normal karyotypes.
• Follow-up of neonates until one year of age was conducted.

Main Results:

• Chromosomal abnormalities were detected in 24.2% of the 248 fetuses.
• CMA identified pathogenic copy number variations (CNVs) in 7.7% of fetuses with normal karyotypes.
• Several known microdeletion/microduplication syndromes and candidate genes associated with VSD were identified.
• Spontaneous closure was observed in 48.7% of VSDs with benign CNVs within the first year.

Conclusions:

• CMA significantly increases the detection rate of submicroscopic imbalances in fetuses with VSD.
• Whole-genome CMA is recommended for fetuses diagnosed with VSD and a normal karyotype.
• Nearly half of VSDs with benign CNVs may resolve spontaneously in infancy.