The Use of Comparative Genomic Hybridization and Fluorescent In Situ Hybridization in Postmortem Pathology Investigation of Congenital Malformations

Chromosomal abnormalities are an important cause of multiple congenital anomalies (MCA). However, conventional cytogenetic analysis using culture is unsuccessful in 10% to 40% of the cases. The purpose of this study was to examine if retrospective chromosomal analysis was possible on paraffin-embedded autopsy material with new techniques, including comparative genomic hybridization (CGH) and fluorescent in situ hybridization (FISH). We investigated 92 patients, including 71 patients with MCA, 17 patients with an isolated congenital anomaly, and 4 normal controls, by conventional CGH analysis and/or FISH. The karyotype was known in 52 cases, of which 26 patients were normal and 26 had chromosomal anomalies. Comparative genomic hybridization or FISH confirmed all but 2 cases, which were not interpretable. In 40 patients the karyotype was unknown but could be analyzed successfully in 36 cases (90%) by CGH. In this series, we found 1 additional chromosomal aberration, 45,X (Turner syndrome). Furthermore, we examined the postmortem material of 12 patients by FISH, confirming a known abnormal karyotype in 9 patients, an abnormal karyotype found by CGH in 1 case, and confirming DiGeorge syndrome (22q11 deletion) in twins. Comparative genomic hybridization and FISH are reliable techniques with which to perform retrospective genetic analysis on paraffin-embedded autopsy material.