Karyotyping and Chromosomal Microarray Analysis in Women Requesting Amniocentesis for Isolated Sonographic Soft...

Chromosomal microarray analysis (CMA) has gained acceptance in prenatal diagnosis, gradually replacing the traditional cytogenetic analysis following amniocentesis or chorionic villi sampling due to its higher resolution than traditional cytogenetics.

The present study investigated the prevalence of major and sub-chromosomal abnormalities in fetuses with isolated ultrasound findings during routine anatomy scan or pregnancies of advanced maternal age after maternal request without medical indication.

Total number of 126 cases were included in total, consisted of two groups; the first group with isolated sonographic soft markers (84 fetuses) and the second group of advanced maternal age (42 fetuses). The group of isolated sonographic markers was further divided per anatomical system affected. The prevalence of genetic aberrations via QF-PCR and CMA was noted.

Clinically significant genetic abnormalities were detected in 12% of the first and 7% of cases in the second group. Interestingly, 40% and 67% of abnormal cases in the first and second group respectively, were identified only after CMA, and they would have missed diagnosis with standard karyotype or QF-PCR alone. Most genetic aberrations were detected in fetuses with findings in the central nervous, craniofacial, cardiovascular, and musculoskeletal system. Sub-microscopic chromosomal aberrations identified only after CMA were gathered in cases with short long bones and in one case with ventriculomegaly.

Even in pregnancies with a first trimester screening low risk result, the risk of identifying a clinically significant CMA aberration is considerable, when an isolated sonographic marker is identified later on in pregnancy or maternal age is advanced.