Twins are traditionally classified as monozygotic (identical) or dizygotic (fraternal). Monozygotic twinning results in genetically identical individuals, whereas dizygotic twins share approximately 50% of their DNA sequence identity, as do full siblings. Sesquizygosity is a third form of twinship, in which individuals share between 50% and 100% of genetic identity. Doctors in Brisbane, Australia have discovered what they say is the world’s second case of sesquizygotic twins — and the first to be identified during pregnancy. The now four-year-old boy and girl are monozygotic on their mother’s side sharing 100% of their mother’s DNA, but are like siblings on their father’s side, sharing only a proportion of their father’s DNA.

“It is likely the mother’s egg was fertilized simultaneously by two of the father’s sperm before dividing,” said University of Queensland’s Professor Nicholas Fisk, who led the fetal medicine team that cared for the mother and twins in 2014.

“The mother’s ultrasound at six weeks showed a single placenta and positioning of amniotic sacs that indicated she was expecting identical twins.”

“However, an ultrasound at 14 weeks showed the twins were male and female, which is not possible for identical twins.”

Sesquizygotic twins were first reported in the United States in 2007. Those twins came to doctors’ attention in infancy after one was identified with ambiguous genitalia.

On investigation of mixed chromosomes, doctors found the boy and girl were identical on their mother’s side but shared around half of their paternal genome.

The Brisbane twins shared about 78% of their paternal DNA.

“If one egg is fertilized by two sperm it results in three sets of chromosomes, one from the mother and two from the father,” said Dr. Michael Gabbett, a clinical geneticist at the Queensland University of Technology.

“Three sets of chromosomes are typically incompatible with life and embryos do not usually survive.”

“In the case of the Brisbane sesquizygotic twins, the fertilized egg appears to have equally divided up the three sets of chromosomes into groups of cells which then split into two, creating the twins.”

“Some of the cells contain the chromosomes from the first sperm while the remaining cells contain chromosomes from the second sperm, resulting in the twins sharing only a proportion rather 100% of the same paternal DNA.”

An analysis of worldwide twin databases pointed to just how rare sesquizygotic twins are.

“We at first questioned whether there were perhaps other cases which had been wrongly classified or not reported, so examined genetic data from 968 fraternal twins and their parents,” Professor Fisk said.

“However we found no other sesquizygotic twins in these data, nor any case of semi-identical twins in large global twin studies.”

“We know this is an exceptional case of semi-identical twins. While doctors may keep this in mind in apparently identical twins, its rarity means there is no case for routine genetic testing.”

A case report on the Brisbane twins was published in the New England Journal of Medicine.

_____

Michael T. Gabbett et al. 2019. Molecular Support for Heterogonesis Resulting in Sesquizygotic Twinning. N Engl J Med 380: 842-849; doi: 10.1056/NEJMoa1701313