A few years ago, Michael Gabbett got a call from a very confused ob-gyn. A woman had come in pregnant with twins who should have been identical—they shared a placenta, meaning they must have split from a single fertilized egg. But doctors could also see, as plain as day on the ultrasound, that one looked like a boy, and the other, a girl.
How could the twins be identical but different sexes? “My initial reaction was, ‘I think your ultrasound is wrong,’” says Gabbett, a clinical geneticist at Queensland University of Technology, in Australia. “They didn’t take too kindly to that.”
The sesquizygotic twins are likely the result of three separate events in the womb, each one rare by itself. First, an egg was fertilized by two sperm, one with an X chromosome, and one with a Y. The usual result is a fetus with three sets of chromosomes rather than the normal two. These fetuses do not survive.
In this case, however, a second unusual thing probably occurred. It seems that the three sets of chromosomes (egg, X sperm, and Y sperm) were able to sort themselves into three types of cells. Two of these cell types were more typical; they each contained one chromosome set from Mom (the X through the egg) and one from Dad (the X or Y from the sperm). The third type only had chromosomes from Dad, one from the X sperm and one from the Y sperm. This last type of cell cannot grow normally. But the two more typical cell types continued to divide and divide as a single ball.
Lastly, this ball of cells split to create two embryos. One grew in the womb to look like an ordinary girl, and the other like an ordinary boy.
Genetically, however, the twins were not so ordinary. The ball of cells had not split neatly into an XX and an XY embryo. The twins are actually chimeras, meaning they both have a mix of XX and XY cells in their body, but in different proportions. The one who looks like a boy has an XX:XY mix of 47:53; the girl has a mix of 90:10. In the 2007 case, one of the twins actually had ambiguous genitalia, which is what first tipped doctors off to something previously unknown about the twins.
Gabbett and his colleague wondered whether more sesquizygotic twins were out there, mistakenly classified as fraternal twins. Unless their DNA has been analyzed, the genetic subtleties are easy to miss. The team decided to analyze the DNA of 968 pairs of presumed fraternal twins and their parents, but they found no evidence of more sesquizygotic twins. It is indeed very rare, as the proposed biological mechanism would suggest. “You’ve got these three very unusual things happen,” Gabbett reiterates. “That’s why it’s so extraordinary.”
The twins in Australia are 4 years old now. One had an arm amputated shortly after birth due to a blood clot unrelated to her chimerism, and later had surgery for an ovarian abnormality that was related to chimerism. Otherwise, they are living healthy lives.
Michael Golubovsky, the biologist who had proposed a mechanism for sesquizygotic twins back in 1984, is not surprised to see a second case. He has also suggested that sesquizygotic twins who are not chimeras—that is, the initial embryo split neatly between two cell types—can exist. And he has proposed yet other scenarios too, in which one sperm divided before fertilization to create sesquizygotic twins.
“The whole process of fertilization is based on extraordinary molecular dialogue,” he wrote in an email. So many things can go awry—a missing chromosome there, an extra set here—and most of those fetuses are not viable. Some are born, with chromosomal abnormalities such as Down syndrome. And some, it appears, can be the result of two sperm fertilizing one egg, and you would never even know it from looking at the resulting children.
Life will find a way, even while deviating far from the standard formula of one egg plus one sperm equals one baby.