Sequizygotic twins: born from the same egg and two different sperms

A study published in February 2019 demonstrates the possibility that an oocyte can be fertilized by two different sperm cells to give rise to twins, more precisely  sequezygous twins.

In everyday life, twins can be homozygous / identical (in this case it is a single egg cell that is fertilized by a single sperm and the fertilized cell then divides into two distinct cells thus giving rise to two identical children), or they can be dizygotic twins /different, i.e. deriving from two distinct oocytes fertilized by one sperm each.

What has been described in the authoritative scientific journal  The New England Journal of Medicine is extraordinary, being a very rare event.

Sesquizygotic multiple pregnancy is an exceptional middle ground between monozygotic and dizygotic twins. Once the amniotic fluid taken from each amniotic sac was analysed, it was seen that the twins were identical on the maternal side but shared 78% of their paternal genome , which made them genetically intermediate between monozygotic and dizygotic: more precisely sequizygotic.

If monozygotic twins are genetically identical individuals (because they derive from a single sperm and oocyte), and dizygotic twins share about 50% of their DNA sequence, as do brothers (ie two single sperm fertilize two distinct oocytes); sequizygotes are a third form of twins, where individuals share between 50% and 100% of their DNA sequence.

The case in detail

During ultrasound scans performed in the first trimester of a 28-year-old woman in her first pregnancy, a diamniotic monochorionic placenta was noted at 6 weeks : one placenta and two amniotic sacs. Everything pointed to a pregnancy of monozygotic (identical) twins. At subsequent ultrasounds, therefore, either two males or two females were expected. Starting at 14 weeks of pregnancies, subsequent ultrasound scans showed sex discordance in structurally normal twins: one fetus appeared to be male and the other female.

How was this possible?

Checking all the ultrasounds done up to that moment, the monochorionic pregnancy was confirmed. Amniocentesis was performed during the second trimester to investigate the genetic heritage of the twins. Each parent provided written informed consent for genomic analyzes of each twin and for analysis of their own genome.

The analyzes confirmed a chimerism in both twins, ie the presence of both 46, XX and 46, XY in each twin.

Twin 1 was diagnosed with 46,XX / 46,XY chimerism in the ratio of 47:53 and of 90:10 in the other twin.

Non-invasive zygosity testing was performed by targeted sequencing of circulating fetal DNA in maternal plasma.

All the results obtained indicated that the twins were neither monozygotic nor dizygotic, but something in between, defined as sequizygotic.

Further genetic investigations confirmed that the twins were 100% identical on the maternal side and 77.7% on the paternal side.

In practice, each twin had three distinct haplotypes deriving from the maternal oocyte and two distinct sperm cells, one carrying the X chromosome and the other the Y chromosome.

Parents were informed of the risk of genital ambiguity and mixed gonadal dysgenesis . The pregnancy continued without problems up to 33 weeks when twin 1 was seen to have low amniotic fluid volume and showed reduced movement. An emergency caesarean section was performed and the twins had normal Apgar scores of 7 to 9 at birth. Histological analysis of the placenta confirmed diamniotic monochorionic placentation.

Postnatal examination and ultrasound of the genital tract confirmed twin 1 as phenotypically male and twin 2 as phenotypically female, with no evidence of sexual ambiguity.