FLUORESCENT IN-SITU HYBRIDIZATION UTILIZATION FOR HIGH-RISK PRENATAL-DIAGNOSIS - A TRADE-OFF AMONG SPEED, EXPENSE, AND INHERENT LIMITATIONSOF CHROMOSOME-SPECIFIC PROBES

OBJECTIVE: The development of fluorescent in situ hybridization chromo some-specific probes has allowed the use of new fetal tissue collectio n techniques, such as fetal cells in maternal blood and coelocentesis - both of which, with current techniques, cannot generate complete kar yotypes. We evaluated chromosome-specific probes for additional potent ial limitations in the setting of a high-risk prenatal diagnosis cente r. STUDY DESIGN: The last 24 months of fetal karyotypes from our prena tal cytogenetics laboratory were analyzed for those abnormalities that should be detectable by chromosome-specific probes and those that wou ld likely be missed. RESULTS: In 6006 karyotypes 207 (3.4%) abnormalit ies were found, of which 104 were common trisomies, 12 triploidies, an d 19 monosomies that would have been detected with current probe combi nations (13, 18, 21, X, and Y) (135/207, 65.2%). Seventy-two abnormali ties (35%) represented other trisomies (16/207, 7.7% for 9, 12, 15, 16 ) and rearrangements (inversions, translocation markers were 56/207, 2 7.1%), which would have been missed. CONCLUSIONS: Use of current fluor escent in situ hybridization chromosome-specific probes protocols woul d 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 pro bes 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 b e questioned until its sensitivity is expanded to identify more subtle and less common chromosomal abnormalities.