Discordance between ultrasound and cell free DNA screening for monosomy X

Cell free DNA (cfDNA) testing has evolved as an important tool in prenatal screening for trisomy 21. It can also be used in screening for monosomy X. We perform a systemic review to determine the detection and false positive in screening for monosomy X and demonstrate a case that offers two possible explanations for the lower screening performance compared to trisomy 21.

A 31-year-old primigravida was referred to us due to an abnormal cfDNA test indicating monosomy X. However, the genitalia was male. An amniocentesis was done that indicated 46,X,idic(Y)(q11.21). SNP array analysis confirmed the Ypter-q11.21 duplication. A phenotypically normal male baby was born at 40 weeks. Postnatal karyotyping of several pregnancy tissues was carried out. While in most samples the karyotype was 46,X,idic(Y)(q11.21), in the four placenta samples and in the amniotic membranes there was mosaicism of 46,X,idic(Y)(q11.21) and 45,X.

A search of the Medline and Embase database was done for articles about screening for monosomy X by cfDNA. We performed a systematic review to assess the detection and false-positive rate.

Seven studies fulfilled the inclusion criteria. In summary, there were 153 pregnancies with monosomy X and 4116 euploid ones. The detection and false-positive rate was 94.1 and 0.53 %.

Although the performance of cfDNA in prenatal screening for monosomy X is better than any other screening test, it is not comparable with invasive testing. One should be aware of the limitations especially if the ultrasound examination is contradictory with the cfDNA results.