A 21-year-old woman was referred for genetic counselling following an abnormal non-invasive prenatal test (NIPT) on maternal request at gestational week 10, which indicated monosomy X. A combined first trimester screening for aneuploidies at 12 weeks of gestation was normal with low risk of trisomy 13,18 and 21. The nuchal translucency thickness was normal (1.5 mm). Chorionic villus sampling was performed at week 13 and revealed a decreased Y chromosome ratio consistent with monosomy X in 43% of the cells, raising the possibility of confined placental mosaicism. To clarify if the mosaicism was present in the fetus, amniocentesis was performed at week 16. Micro-array of the fetal cells revealed fetal monosomy X mosaicism consistent with the presence of two cell lines present 65% 45,X and 35% 46,XY.

An anomaly scan at week 16 showed normal male genitalia, and no signs of Turner stigmata on ultrasound (figure 1). Genetic counselling was provided, and possible scenarios of fetal affection was discussed with the parents, including risk of ambiguous gender, male fetus with possible infertility or female gender with TS.

A second-trimester scan at week 20 confirmed normal fetal growth and anatomy of a male fetus. Fetal growth restriction was identified at gestational week 29 and the fetus remained growth restricted (ranging between -27% to -17%) until birth. The fetus was delivered by caesarean section in gestational week 36+3 due to flow class 1-2 in the umbilical artery, reduced fetal movements and pathological CTG.

The boy was born with a birth weight of 2445 grams. The postnatal examination was normal, and male genitalia appeared normal with both testes present in the scrotum.

Counselling of parents following prenatal diagnosis of 45,X/46,XY mosaicism is difficult. The prognosis is highly variable and the degree of mosaicism in amniotic fluid is a poor predictor of outcome⁵. In addition, current evidence on outcome is highly diverging whether they are based on prenatal or postnatal diagnosis²⁶⁷.

In retrospective studies of outcome in prenatally diagnosed 45,X/46,XY fetuses, approximately 89-95 % of the fetuses have normal appearance of the male genitalia, and only 5-10 % have ambiguous or female genitalia⁵⁶⁸. However, the studies also report high rates of abortion (up to 83%), which is either due to termination of pregnancy or to fetal loss possibly due to a more severe phenotype⁵⁸⁹. In contrary, large retrospective studies of monosomy X mosaicism 45,X/46,XY have demonstrated that up to 50% of cases are diagnosed postnatally¹⁰. Most of these cases are found due to either short stature in childhood or infertility in adulthood⁷¹¹¹². Hence, postnatal detection of monosomy X mosaicism may reflect cases with milder phenotypes¹⁰. In cases with 45,X/46,XY with normal external male genitalia, up to 27% have abnormal gonadal tissue with increased risk of carcinoma even before puberty⁵¹⁰. In contrary, other

studies report that the majority of cases with 45,X/46,XY have sufficient gonadal function to achieve spontaneous puberty, but may require fertility treatment later in life⁷.   

The marked variation in phenotypic appearance and the diversity in outcome in previous studies make prenatal assessment and counselling complex, since there is no consistent correlation between karyotype and phenotype. This case is noteworthy since the fetus, despite a high percentage of monosomy X cells, had no structural abnormalities and normal development of male genitalia.

This case contributes to the broader understanding of the diagnostic complexities and dilemmas in genetic counselling following a prenatal diagnosis of monosomy X mosaicism in 45,X/46,XY fetuses.