Chromosome abnormality are common genetics disorders causing spontaneous abortion, fetus aberration or birth defects6, 7. However, there are no effective methods to treat this kind of abnormal chromosome disorders. Nowdays with the rapid development of technology, amniocentesis and subsequent karyotype analysis is the gold standard for prenatal disgnosis, which is an important way to confirm and prevent aberrant pregnancies8, 9. Chromosome mosaicism would cause varying degrees of fetal abnormalities according to the mosaic propotion. Sex chromosome mosaicism will lead to hermaphroditism and psychiatric disorders10.
Early work indicated that sex chromosome mosaic is the most common type of mosaicism, which involved either a loss or gain of one sex chromosome, with the proportion of nearly a half of all kinds of mosaicism, including sex chromosome mosaicism, autosomal mosaicism and marker chromosome mosaicism1. Out of the 14046 cases of fetal karyotype analysis, 46 fetus were found sex chromosome mosaicism, the sex chromosome mosaicism proportion is 0.327%, which is a little lower than that of others’ research in China reported in 201811.
For all these 46 cases, their prenatal diagnostic indications are different, a half of them were the numerical abnormality of sex chromosome by NIPT, which could increase the sex chromosome mosaicism proportion among general pregnant women, because of the high accuracy rate of NIPT. 26% of the 46 pregnant women were grouped into high-risk serum screening, other high risk indications are less than or only 8.7%. In lights with these findings, we would summarize that of the proportion of sex chromosome mosaicism is less than 0.327% of all the pregnant women in China. So when they had high risk in the numerical abnormality of sex chromosome by NIPT, they must perform the amniocentesis to get accurate cytogenetic diagnosis to exclude sex chromosome abnormality due to its definite pathogenicity.
Among these mosaic cases, 45,X(Turner Syndrome) is the most common chromosome abnormality. 31 out of 46 were 45, X mosaicism, which usually causes infertility, cardiac and kidney malformation, and ear and hearing problems12. Sex chromosome trisomies mosaicism, including 47,XXY, 47,XXX, 47,XYY, that is an extra X or Y chromosome in karyotype, are less than 45,X mosaicism.
47,XXY(Klinefelter syndrome) usually leads to varying clinical manifestation, like infertility, small testes, and problems with psychological development, lower IQ, and delayed speech development13. 47,XXX(Triple X) girls are at high risks for difficulties in language, neuromotor and learning skills and behavior problems14. 47,XYY usually shows worldwide attention deficit hyperactivity disorder symptoms, comprised language development, phychotic disorder15, 16. Among all these mosaicisms, only one fetus have 48,XXXX mosaicism karyotype. It was reported that girls with tetrasomy X had dysmorphic facial features, varying degrees of cognitive dysfunction, speech and language disorders and skeletal and connective tissue disorders17. There are sex chromosomal or autosomal structure abnormality for 6 cases, including inversion, translocation, isochromosome, dicentric X chromosome. One case is the short arm of chromosome 22 increased with the length of the body stalk (22sptk+), which is normal chromosome variation.
It has been indicated that Turner syndrome, Klinefelter syndrome, and 45,X mosaicism were main factors associated with parental dicisions to terminate an affected pregnancy18. In our study, most pregnant women prenatal diagnosed 45,X/46,XX mosaicisms choose to abort their pregnancies, except one case with 45,X[5]/46,XX[95] karyotype, because of high proportion of normal karyotype. However, as regard to 45,X/46,XY karyotype,when the proportion of 46,XY was higher than 80%, almost all women choose to continue the pregnancy. This may be due to the traditional Chinese demand for boys. Especially for one pedigree the abnormal karyotype was 45,X/46,XX, and the mosaic proportion was 46% and 54%, respectively, the family urged to continue the pregnancy even the doctor adviced them to abort.
If the karyotypes of the three sex chromosomes(47,XXX,47,XXY,47,XYY) are chimeric with the normal two sex chromosomes(46,XX,46,XY), pregnant women usually choose to induce labor,but when the proportion of normal karyotypes are higher than 80%,pregnant women would continue the pregnancies. When the karyotypes of the chimeras are all abnormal karyotypes, that is, either the number or structure of sex chromosomes are abnormal or the structure of autosomes is abnormal, pregnant women would choose to induce labor. When there are three types of karyotypes in the chimera, pregnant women choose to induce labor. Three pedigrees lost contact, and we could not know their choices.
In lights with these findings, we would suggest the fetus with mosaic sex chromosome karyotype abort their pregnancies if the abnormal karyotype was higher than 80%.
However, there are many potential factors associated with parental decisions regarding abnormal sex chromosome pregnancy in our research, we just did a simple follow-up, more studies need to be explored.
Concluding, if the pregnant women have clear incidences of prenatal diagnosis, they had better to follow the doctors' advices to conduct prenatal cytogenetic diagnosis. Prenatal cytogenetic diagnosis by amniocentesis is an accurate and convenient method and helps to avoid the delivery of fetuses with chromosomal diseases and reduce the risk of fetal malformation.