Post‐mortem rapid aneuploidy testing for holoprosencephaly

Background Abortion and fetal death are common in fetuses with holoprosencephaly, so genetic examinations often have to be made in a post‐mortem setting. The efficiency of the conventional karyotyping using cultured fibroblasts in these situations is limited due to frequent culture failure. In the current study, archived cases of holoprosencephaly, where post‐mortem genetic evaluation was requested and sufficient frozen material was available, were reevaluated using the quantitative fluorescence polymerase chain reaction (QF‐PCR) technique. Methods Testing for aneuploidies of chromosomes 13, 15, 16, 18, 21, 22, X, and Y with the QF‐PCR technique was carried out on DNA isolated from archived frozen chorionic villi in seven cases of holoprosencephaly. Results QF‐PCR was successful in all seven cases. Two cases of trisomy 13, two cases of triploidy, and one case of trisomy 18 was found meaning a 71% diagnostic yield. The success rate of QF‐PCR (100%, 7/7) was superior compared to conventional karyotyping (43%, 3/7). Conclusions Rapid aneuploidy testing using the QF‐PCR technique is a simple, reliable, time‐ and cost‐effective method sufficient to conclude the etiologic investigation in the majority of holoprosencephaly cases post‐mortem.