The frequency of CNVs in a cohort population of consecutive fetuses with congenital anomalies after the termination of pregnancy

The implementation of molecular karyotyping has resulted in an improved diagnostic yield in the genetic diagnostics of congenital anomalies, detected prenatally or after the termination of pregnancy. However, the systematic epidemiologic ascertainment of copy number variations in the etiology of congenital anomalies has not yet been sufficiently explored.

Our systematic approach of ascertaining congenital anomalies resulted in explaining the etiology of congenital anomalies in 47% of fetuses after the termination of pregnancy. By using array comparative genomic hybridization, we found that copy number variations represent an important part in the etiology of multiple, as well as isolated congenital anomalies, which indicates the importance of analyzing copy number variations in the diagnostic approach of fetuses with congenital anomalies after the termination of pregnancy.

Consecutive fetuses, altogether 204, with major single or multiple congenital anomalies were ascertained by using the SLOCAT registry for the period from 2011 to 2015. After excluding aneuploidies by using conventional karyotyping or Quantitative Fluorescence-Polymerase Chain Reaction, array comparative genomic hybridization was performed for the detection of copy number variations.

We identified pathogenic or likely pathogenic copy number variations in 14 fetuses (6.8%); 2.9% in fetuses with isolated, and 3.9% in fetuses with multiple congenital anomalies. Additionally, aneuploidies and major structural chromosomal abnormalities were detected in 40.2%.