Cytogenetics and Molecular Investigations detect a Mosaic Variant of Turner Syndrome only Suspected by Non-Invasive Prenatal Testing: Two Case Reports with Negative Ultrasound Examinations

Abstract

Prenatal testing has been moving towards non-invasive methods to determine fetal risk for genetic disorders. Numerous studies have focused the attention on common trisomies; although the detection rate (DR) for trisomy 21 is high (over 95%), the accuracy regarding the DR for trisomies 13 and 18 has come under scrutiny. The testing has been applied to sex chromosome aneuploidies, but many studies have shown that it is not as effective as it is for common trisomies. Although non-invasive prenatal test (NIPT) has become a standard screening procedure for all pregnant women, invasive sampling procedures remain important in confirming NIPT-positive findings. In the present study, we report discordant results of Turner syndrome (TS) mosaicism between NIPT and karyotyping. A 35-year-old pregnant woman underwent NIPT, and a probable risk for Xp deletion was indicated. Subsequently, amniocentesis was performed. The karyotype was identified as mos 45,X [28]/46,X,i(X)(q1.0)[5]. In the second case, a 33-year-old woman underwent amniocentesis after a positive NIPT that indicated a probable risk for monosomy X. The result was mos 45,X [8]/46,XY[8]. Since NIPT is a screening test, the possibility of false-positive or false-negative results should always be considered. We underline the importance of pre/post detailed counseling. Furthermore, women with abnormal NIPT results should undergo immediate amniocentesis that remains the only tool for a correct diagnosis of sex chromosome aneuploidies.

Keywords: Counselling; Turner syndrome; mosaicism; non-invasive prenatal test; prenatal diagnosis.

Figure 1:

Chromosome microarray analysis on amniotic cells. The results demonstrated a single copy gain of 52.27 Mb on the Xp arm.

Figure 2:

GTG-banding showed a karyotype of 46,X,i(X)(q10).

Figure 3:

FISH for interphase nuclei from the amniotic fluid. A positive SRY signal indicated by the red light is found at the terminal Y p-arm. The centromere of the X chromosome is shown by the green light. Interphase nuclei: the one with one green signal and the other with red and green signals.