Residual risk of fetal cytogenetic abnormalities in interphase fluorescence in situ hybridization for amniocytes in second trimester: analysis of 2 837 cases

Abstract

Objective To evaluate the residual risk (i.e. failure risk in detecting aneuploidies abnormalities except for chromosome 13, 18, 21, X and Y) of cytogenetic abnormalities using interphase fluorescence in situ hybridization (FISH) for the second-trimester amniocytes. Methods The results of interphase FISH and conventional karyotyping of 2 837 consecutive amniotic fluid specimens were analyzed retrospectively. Probes for chromosomes 13, 18, 21, X and Y were used. The detection rate and residual risk for interphase FISH were calculated for the following three major clinical indications for prenatal diagnosis (advanced maternal age, abnormal maternal serum screening indicating an increased risk for trisomy 18 or trisomy 21, and ultrasound abnormalities). Results Consecutive interphase FISH and karyotyping of second-trimester amniocytes for prenatal diagnosis were performed from January 1, 2010 to July 31, 2013. Among the 2 837 cases, 85 (3.0%) cases with abnormal karyotypes were found, including 73 cases of aneuploidies involving chromosome 13, 18, 21, X and Y, which were considered detectable by interphase FISH; 12 cases of chromosomal anomalies, other than aneuploidies of chromosome 13, 18, 21, X and Y, were diagnosed after karyotyping and were not detected by interphase FISH, including six cases of balanced rearrangements, five cases of imbalanced rearrangements, and one case of pseudomosaic of trisomy 20. Of these 12 chromosomal anomalies, three cases of imbalanced rearrangements involving chromosome 21 showed positive FISH results, and the other nine cases showed negative FISH results among which four case of hereditary balanced rearrangemerts and two cases of novel balanced rearrangements. The total detection rate for interphase FISH was 89.4% (76/85), the misdiagnosis rate of chromosome abnormalities was 14.1%(12/85), and the residual risk was 0.43% (12/2 761) following interphase FISH of the second-trimester amniocytes. Conclusions Interphase FISH is a useful adjunct to conventional karyotyping, but should not be regarded as a replacement for karyotyping as too many structural chromosomal abnormalities will be missed. Providing patients with a detection rate and residual risk during counselling may help them understand the advantages and limitations of interphase FISH in their prenatal diagnostic evaluation. Key words: In situ hybridization, fluorescence; Chromosome aberrations; Prenatal diagnosis; Pregnancy trimester, second; Amniotic fluid