When Yaakov and Aliza found out that they were expecting twins, they were overwhelmed and excited. But at the end of the first trimester, their joy turned into worry. Aliza had taken some standard prenatal tests, and instead of the usual “all-clear,” the doctor asked to meet with them. One of their babies showed signs of trisomy 13—an extra copy of her thirteenth chromosome.
The condition causes severe deformities that are incompatible with life. Most babies don’t survive to term, and for those who do, the average lifespan is less than two weeks.
It was essentially a death sentence.
In most cases, the parents of a trisomy 13 fetus can wait for the baby to be born. In this case, however, since Aliza was expecting twins, the doctor gave them only one option. They would have to abort one baby in order to save the other—and as soon as possible. Otherwise, the healthy baby might be affected.
Still, Aliza’s doctor was cautious. “It’s just an initial blood test, and with twins the numbers can sometimes get funny.” He recommended that she undergo chorionic villus sampling, or CVS, in which a few cells are removed from the placenta for DNA analysis.
Yaakov and Aliza researched the top maternal-fetal practices in New York and found one of the best doctors in the country, Dr. Andrei Rebarber. Dr. Rebarber had nearly 30 years of experience, offices all over the city, patients from all over the world—and a lot of experience with trisomy 13. They scheduled the test as early as they could and made the drive down from Monsey.
Yaakov was confident that the initial results had been a mistake and that everything would be fine. Aliza, though, was nervous—and for good reason. It can take weeks to get CVS test results back, but her preliminary results were available two days later. They were devastated to learn that baby B did have trisomy 13.
Yaakov and Aliza spent hours that night reading about trisomy 13 online, looking for a ray of hope, some cause for optimism. There wasn’t any. The next morning found them once again in Dr. Rebarber’s office. The preliminary results, he told them, were 99 percent accurate.
They jumped on that number—99 wasn’t 100! But even that sliver of hope was not to be their salvation.
“In less than 1 percent of cases,” the doctor explained, “the baby has a mosaic form of the condition, meaning that half the cells are healthy and half are affected. But even then the baby can’t live more than a few months. I would advise selective reduction—terminating baby B as soon as possible so that baby A isn’t affected. I’ve had Orthodox Jewish patients before, and I know that the rabbis permit it in such cases. Please consult with whomever you need to, and then call my office to schedule the procedure.”
Back in the car, a stunned Yaakov called his rav, who put them through to a rav who was an expert in these types of sh’eilos. It was late Friday afternoon, and time was of the essence. Any delay could be harmful to the other baby.
“In order to save the twin you can undergo the procedure,” the rav told them.
But it was too close to Shabbos, and Monday was a legal holiday. The soonest they could schedule the procedure was Tuesday.
It was a long, emotional weekend. They hadn’t yet shared the tragedy with anyone in their families and would have to say goodbye to their baby alone. Yaakov was in touch with his rebbe in Israel, who in turn consulted with the Amshinover Rebbe. He reminded them that “mei’ayin yavo ezri”— Hashem’s yeshuah [G-d's salvation] can come from ayin, nothingness.
[The publicly accessible article stops here. What follows is a summary of the remainder of the article which requires subscription.]
Yaakov and Aliza listened to music on their many trips for evaluation. One song became their anthem, “Hashem is found even in extreme concealment.”
By Tuesday morning Yaakov and Aliza had come to terms with their loss. They were comforted by the blessing of having one healthy child. Upon arrival at the doctor’s office, another ultrasound was done. The doctor upon viewing this told the couple that ordinarily a trisomy 13 fetus of this gestation would have abnormal growths on the spine, which were not there in the affected fetus. Dr. Rebarber suggested this might be a very rare case of mosaicism for trisomy 13, where chances for survival were still slim.
Four days later, the full genetics report from chorionic villus sampling returned, confirming mosaicism. Only 3/20 cells tested had trisomy 13. The usual trisomy 13 mosaic has fifty per cent of the cells affected.
Dr, Rebarber then suggested sampling cells from the amniotic fluid in the event that this was an extremely rare case where only the placenta had trisomy 13 cells.
On the night of Purim, as joyous Jewish holiday, Dr. Rebarber called to say, “It’s a Purim miracle. The trisomy is confined to the placenta. G-d willing, your baby will be all right. Enjoy the holiday.”
The remainder of the pregnancy was carefully monitored. Aliza gave birth to two healthy girls.
By Rabbi Yoel Gold
Hall AL, Drendel HM, Verbrugge JL, Reese AM, Schumacher KL, Griffith CB, Weaver DD, Abernathy MP, Litton CG, Vance GH. Positive cell-free fetal DNA testing for trisomy 13 reveals confined placental mosaicism. Genet Med. 2013 Sep;15(9):729-32. doi: 10.1038/gim.2013.26. Epub 2013 Mar 14. PMID: 23492874.
Purpose: We report on a case in which cell-free fetal DNA was positive for trisomy 13 most likely due to confined placental mosaicism. Cell-free fetal DNA testing analyzes DNA derived from placental trophoblast cells and can lead to incorrect results that are not representative of the fetus.
Methods: We sought to confirm commercial cell-free fetal DNA testing results by chorionic villus sampling and amniocentesis. These results were followed up by postnatal chromosome analysis of cord blood and placental tissue.
Results: First-trimester cell-free fetal DNA test results were positive for trisomy 13. Cytogenetic analysis of chorionic villus sampling yielded a mosaic karyotype of 47,XY,+13/46,XY. G-banded analysis of amniotic fluid was normal, 46,XY. Postnatal cytogenetic analysis of cord blood was normal. Karyotyping of tissues from four quadrants of the placenta demonstrated mosaicism for trisomy 13 in two of the quadrants and a normal karyotype in the other two.
Conclusion: Our case illustrates several important aspects of this new testing methodology: that cell-free fetal DNA may not be representative of the fetal karyotype; that follow-up with diagnostic testing of chorionic villus sampling and/or amniotic fluid for abnormal test results should be performed; and that pretest counseling regarding the full benefits, limitations, and possible testing outcomes of cell-free fetal DNA screening is important.
Hayata K, Hiramatsu Y, Masuyama H, Eto E, Mitsui T, Tamada S. Discrepancy between Non-invasive Prenatal Genetic Testing (NIPT) and Amniotic Chromosomal Test due to Placental Mosaicism: A Case Report and Literature Review. Acta Med Okayama. 2017 Apr;71(2):181-185. doi: 10.18926/AMO/54988. PMID: 28420901.
We experienced a case of advanced maternal age in which a fetus was found to be positive for trisomy 18 at re-examination following indeterminate non-invasive prenatal genetic testing (NIPT), the amniotic fluid chromosomal test revealed a normal karyotype, and confined placental mosaicism (CPM) was observed in an SNP microarray analysis of the placenta. The child was born with no defects or complications. In the present case, the result of the original NIPT at week 15 of pregnancy was indeterminate and the subsequent re-examination result was positive; since the definitive normal diagnosis was not reported until the latter half of week 21, the pregnant patient was subjected to psychological stress for a long period of time. The problem with NIPT is that most of the fetus-derived cell-free DNA in the maternal blood is not derived directly from the fetus but from the villus cells of the placenta, leading to indefinite diagnoses; for that reason, the pregnant patient was subjected to psychological stress for a long period of time. Of the 18,251 cases undergoing NIPT in the past 2 years in Japan, 51 had indeterminate results; this was the second case in which a subsequent re-examination gave a positive result for trisomy 18.
Liu XY, Zhang HG, Wang RX, Chen S, Yu XW, Liu RZ. Placental mosaicism for Trisomy 13: a challenge in providing the cell-free fetal DNA testing. J Assist Reprod Genet. 2014 May;31(5):589-94. doi: 10.1007/s10815-014-0182-7. Epub 2014 Feb 5. PMID: 24497298; PMCID: PMC4016375.
Purpose: We investigated the disagreement between the positive cell-free fetal DNA test for trisomy 13 and the standard cytogenetic diagnosis of one case.
Methods: Cell-free fetal DNA testing was performed by massively parallel sequencing. We used conventional cytogenetic analysis to confirm the commercial cell-free fetal DNA testing. Additionally, postnatal fluorescent in situ hybridization (FISH) testing was performed on placental tissues.
Results: The cell-free fetal DNA testing result was positive for trisomy 13. G-banded analysis of amniotic fluid was normal, 46, XY. FISH testing of tissues from four quadrants of the placenta demonstrated mosaicism for trisomy 13.
Conclusions: A positive cell-free fetal DNA testing result may not be representative of the fetal karyotype because of placental mosaicism. Cytogenetic analysis should be performed when abnormal cell-free fetal DNA test results are obtained.