Quantitative fluorescent polymerase chain reaction versus cytogenetics: Risk-related indication and clinical implication of nondetected chromosomal disorders

Background: The rapid detection of aneuploidies by quantitative fluorescent polymerase chain reaction (QF-PCR) allows reliable prenatal diagnosis of trisomies 21, 18, and 13. Discussion has been raised as to whether single QF-PCR could be an alternative to traditional cytogenetic karyotyping for certain referral categories. Objective: To evaluate an indication-based classification of cases at risk of missing clinically relevant chromosomal disorders by QF-PCR. Methods: From October 1999 to November 2003, 4,682 of 14,123 patients referred for amniocentesis decided to have QF-PCR as a rapid adjunct to conventional cytogenetic evaluation. Patients were classified according to the risk of missing chromosomal abnormalities by QF-PCR based on anamnestic risk and ultrasound prior to amniocentesis. The results in these two defined categories were compared in relation to the clinical significance of cytogenetic results. Results: QF-PCR and conventional cytogenetic analysis had concordant results in 4,617 of 4,682 (98.6%) cases. Thirty-six of 110 (32.2%) clinically significant chromosomal abnormalities were missed by QF-PCR. Patients classified not to be at risk of missing chromosomal abnormalities using QF-PCR had a residual risk of 1/166 (0.6%) for chromosomal distortions of clinical significance. Conclusion: Classification by anamnestic and sonographic data does not specifically identify patients at risk of structural abnormalities. Clinical relevance of the nondetected anomalies essentially justifies traditional karyotyping regardless of risk classification. Copyright (c) 2006 S. Karger AG, Basel.