Detecting genomic imbalances in prenatal diagnosis: main hurdles and recent advances

Chromosome analysis from cells obtained by either amniocentesis or chorionic villi sampling has allowed for the detection of large clinically consequential genetic imbalances throughout the genome for several decades. The newer technologies of fluorescence in situ hybridization, quantitative fluorescence polymerase chain reaction (QF-PCR) and multiplex ligation-dependent probe amplification have provided a more rapid and less expensive focused detection of the most common clinically significant chromosome aneuploidies. Array comparative genomic hybridization (CGH) has recently proved invaluable for the detection of genetic imbalances in the postnatal population. Recent studies on the utility and feasibility of array CGH on prenatal samples indicate this technology will increase the detection of clinically significant genomic abnormalities. Advances have also occurred in the use of cell-free fetal nucleic acids in maternal serum for screening of common aneuploidies.

Within this review, we discuss the utility of each of these technologies, the role they currently play, and the authors' opinions on the future direction of prenatal genetic testing for chromosomal imbalances.

QF-PCR and array CGH are likely to play significant roles in the future of prenatal diagnostics as they are more specifically targeted for the individual clinical indications. More studies are needed to determine the appropriate use of fetal cell-free nucleic acids in maternal serum.