Fluorescent in situ hybridization utilization for high-risk prenatal diagnosis: a trade-off among speed, expense, and inherent limitations of chromosome-specific probes.

Abstract

The development of fluorescent in situ hybridization chromosome-specific probes has allowed the use of new fetal tissue collection techniques, such as fetal cells in maternal blood and coelocentesis--both of which, with current techniques, cannot generate complete karyotypes. We evaluated chromosome-specific probes for additional potential limitations in the setting of a high-risk prenatal diagnosis center. The last 24 months of fetal karyotypes from our prenatal cytogenetics laboratory were analyzed for those abnormalities that should be detectable by chromosome-specific probes and those that would likely be missed. In 6006 karyotypes 207 (3.4%) abnormalities were found, of which 104 were common trisomies, 12 triploidies, and 19 monosomies that would have been detected with current probe combinations (13, 18, 21, X, and Y) (135/207, 65.2%). Seventy-two abnormalities (35%) represented other trisomies (16/207, 7.7% for 9, 12, 15, 16) and rearrangements (inversions, translocation markers were 56/207, 27.1%), which would have been missed. Use of current fluorescent in situ hybridization chromosome-specific probes protocols would have detected only 65% of chromosome abnormalities in our high-risk population. Incomplete ascertainment must be weighed against the cost and speed of fluorescent in situ hybridization chromosome-specific probes when comparing it with traditional karyotyping. Although this new technique may prove useful in low-risk screening programs (fetal cells in maternal blood), its current use in high-risk populations should be questioned until its sensitivity is expanded to identify more subtle and less common chromosomal abnormalities.