Identical twins are formed from two different eggs and two different sperm

Doctors have documented what they say is only the world's second known case of "semi-identical" twins.

The boy and the girl, now four, from Brisbane, in Australia, are identical on their mother's side.

But they share only a proportion of their father's DNA - placing them, genetically, somewhere between fraternal and identical twins.

Experts say the phenomenon is extremely rare - embryos such as these often do not survive.

• The twins who have different dads - BBC News
• Semi-identical twins discovered

Prof Nicholas Fisk, who led the team that cared for the mother and twins at the Royal Brisbane and Women's Hospital in 2014, said the discovery was made through a routine pregnancy scan.

It is the first time semi-identical twins have been identified during pregnancy.

The first-time mother was 28 at the time and had conceived naturally, doctors said.

The case is being reported on in The New England Journal of Medicine.

"The mother's ultrasound at six weeks showed a single placenta and positioning of amniotic sacs that indicated she was expecting identical twins," Prof Fisk said.

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

How did it happen?

Identical, or monozygotic, twins occur when a single egg, fertilised by a single sperm, divides and makes two babies.

These twins will be the same sex and share the same genes and physical features.

Non-identical, or dizygotic, twins occur when two separate eggs are fertilised, each by a different sperm, and develop in the womb at the same time.

These twins can be the same or different sexes and are no more alike than any brother or sister, despite being born together.

In this case of semi-identical, or sesquizygotic, twins, the egg is thought to have been fertilised simultaneously by two sperm before it divided.

If one egg is fertilised by two sperm, it results in three sets of chromosomes, rather than the standard two - one from the mother and two from the father.

And, according to researchers, three sets of chromosomes are "typically incompatible with life and embryos do not usually survive".

The identity of the twins has not been revealed.

What causes twins?

Non-identical twins are more common than identical twins and are much more likely to run in families.

Older mothers are also more likely to have non-identical twins because they are more likely to release more than one egg during ovulation.

Infertility treatment - IVF - can increase the chance of twins, as more than one embryo may be put into the womb.

According to the Twins and Multiple Births Association (Tamba), about 12,000 twin births occur each year in the UK.

'Exceptional case'

The first documented case of half-identical twins was in the US in 2007.

Prof Fisk said an analysis of worldwide twin databases highlighted just how rare sesquizygotic twins were.

He and his colleagues examined genetic data from 968 fraternal twins, as well as a number of large global studies, but found no other case of sesquizygotic twins.

"We know this is an exceptional case of semi-identical twins," Prof Fisk added.

"While doctors may keep this in mind in apparently identical twins, its rarity means there is no case for routine genetic testing."

Twins that look exactly alike are typically referred to as "identical" twins. However, a more accurate term is "monozygotic." Monozygotic twins share almost exactly the same genes as they are formed from the same embryo. Learn more about monozygotic twins, including how they are formed and other interesting twin facts.

How Are Monozygotic Twins Formed?

Monozygotic twins happen when a single fertilized egg divides into two. From there, two embryos grow into two babies. Monozygotic ("mono" means one and "zygote" means fertilized egg) is the term used to describe this process.

This type of twin formation begins when one sperm fertilizes one egg (oocyte). As the fertilized egg (called a zygote) travels to the uterus, the cells divide and grow into a blastocyst. In the case of monozygotic twins, the blastocyst then splits and develops into two embryos.

In contrast, dizygotic (fraternal) twins form when two separate eggs are released and fertilized by two sperm. Then those resulting embryos develop at the same time, but individually. Dizygotic twins are common with fertility treatments that cause multiple eggs to be released or more than one embryo to be transferred into the uterus.

What Are My Chances of Having Twins?

Why Do Monozygotic Twins Occur?

Overall twinning rates (monozygotic plus dizygotic) vary globally. In the United States, for example, the rate of twin births has declined in the last few decades and monozygotic twins make up a small percentage of the overall twin birth rate.

However, most of the variation is due to differences in dizygotic twin rates. The rate of monozygotic twins is very consistent around the world: about 3 to 5 in every 1,000 twin births.

In some tribal and isolated populations, monozygotic twins seem to run in the family or in the greater tribe. It remains unknown if genetics are at play or the environment, but it's likely that something in the environment triggers the split, or it occurs randomly.

What About Family History?

Contrary to popular belief, the chances of having monozygotic twins are most often not related to your family history. If there is more than one set of identical twins in a family, it is probably due to luck or external environmental factors. Some genetic mutations have been identified that increase the chance of monozygotic twins, but these are very rare.

However, dizygotic twins do run in families. This is mainly thought to be due to genes that increase the number of eggs released.

Higher Frequency with IVF

Interestingly, in vitro fertilization (IVF) appears to increase the likelihood of having monozygotic twins.

IVF research has given us some insight into how identical twins form. IVF embryos are more likely than naturally conceived embryos to split into identical twins. A fertility doctor can transfer just one embryo—in hopes of reducing the risk of non-identical twins—but identical twins may still occur, and more frequently than in the general population.

In normal embryo development, a fluid-filled cavity grows inside the embryo. This is known as the blastocoel. Also inside the embryo is a collection of cells known as the inner cell mass, which is a collection of cells that will eventually form the fetus.

During IVF, the blastocoel may collapse on itself. While this typically destroys the embryo, sometimes the embryo survives, causing the inner cell mass to split into two. The two inner cell masses lead to the development of twins.

The embryo is initially kept in an artificial solution in the lab. While scientists have done their best to make this environment as close to natural as possible, it isn't exactly the same environment as inside a woman’s reproductive system. Perhaps this solution increases the risk of collapse.

Opinions differ on when to transfer the embryo into the woman’s uterus. It seems that transferring the embryo later may slightly increase the odds of identical twinning.

Understanding IVF Treatment Step By Step

The Genetics of Twinning

It was once thought that monozygotic twins shared the exact same DNA. But this isn’t true because every time cells split, there is a chance of mutations, starting as early as the first split. This is one reason why identical twins are at an increased risk of congenital diseases.

After one split, individual cell masses continue splitting on their own. With every split, there is another chance of mutation. Usually, by birth, the genes of twins are extremely similar but not identical. Over time, genetic dissimilarities continue to increase. This is due to epigenetics—the way the environment changes how our DNA is expressed.

Some studies have found that slight DNA differences are more common in older identical twins than in very young identical twins. Spending more time apart in different environments is a likely contributor.

Even though monozygotic twins look alike and share similar characteristics, they are not clones. The two embryos have the same genetic components to start, but slight differences develop over time.

Identical Twins…But Different Sexes?

When twins are born with genetically different sexes (one twin is genetically male and the other is genetically female) they are usually dizygotic. Monozygotic twins are typically born as the same genetic sex.

However, while it's extremely rare, it is possible for monozygotic twins to be two different sexes. This goes back to the idea that genetic mutations can occur from the very first split.

If an egg carries two X chromosomes (when a normal egg should carry just one X chromosome) and is fertilized with a Y sperm, you can get an XXY embryo. This is also known as Klinefelter syndrome.

However, what happens if that XXY embryo splits into monozygotic twins? You can end up with one twin with XX expression (female), and the other with XY (male). This situation is so rare that it has only been described in medical literature four times.

There is another (rare) way to have identical twins of different sexes. If you have an egg with one X chromosome, and sperm with a Y chromosome, you would typically get a boy (XY). Normally, if this embryo split into twins, you’d get identical twin boys. However, it’s possible for one twin to result with only the X chromosome (usually written as XO), and the other XY.

Thus, one twin will be a girl (with the congenital disorder known as Turner syndrome), and the other twin will be a boy. All this said, these situations are so rare that it's safe to assume that 99.999% of boy-girl twins are not monozygotic twins.

Pregnancy and Congenital Abnormalities

Semi-Identical and Conjoined Twins

A rare form of monozygotic twins is semi-identical or half-twins, which occurs when two separate sperm fertilize one egg. This is another situation where you can get two sexes, but these are not truly “identical” twins since you started with two and not one sperm fertilizing the egg.

The first case was only identified by researchers in 2007, and another was found in 2014. In these rare cases, scientists hypothesized that the egg was fertilized by two separate sperm.

At first glance, it appeared that the twins would be identical, but they were born as genetically different sexes. When the twins' DNA was examined more closely, it became apparent that each twin actually had both XX (female) and XY (male) chromosomes.

Conjoined twins are another rare form of monozygotic twinning, where the twins do not fully separate when the zygote splits. They may share multiple organs. Most conjoined twins die in utero or are stillborn.

Monozygotic Twins in the Womb

Most of the time, monozygotic twins have separate amniotic sacs but share one placenta. The technical term for this is monochorionic-diamniotic (or Mo-Di), and it occurs between 60% and 70% of the time with monozygotic twins.

Sharing one placenta increases risks to the pregnancy, due to the possibility of twin-to-twin transfusion syndrome. The pregnancy must be watched very carefully if Mo-Di twins are diagnosed.

Another possibility is for the twins to each have their own placenta and amniotic sac. This is known as dichorionic-diamniotic (or Di-Di) twins. The risks in a Di-Di pregnancy are lower than with a Mo-Di pregnancy. There is a misconception that Di-Di twins are always fraternal (non-identical), but this is not true. About 30% of monozygotic twins are Di-Di.

The riskiest combination is when twins share one amniotic sac and one placenta. This only occurs in monozygotic twins and never with non-identical twins.

This is known as monochorionic-monoamniotic (Mo-Mo) twins, and it is relatively rare, occurring in only 5% of twin pregnancies. With Mo-Mo twins, the biggest risk is that the babies can become entangled in the umbilical cords. There is also a risk of twin-to-twin transfusion syndrome and a higher risk of prematurity.

Early studies found that only 50% of Mo-Mo twins survived, but later studies have found more encouraging results, with the perinatal (the period immediately before and after birth) mortality rate closer to 20%.

Determining Whether Twins Are Identical

The only way to be sure about zygosity is with a DNA test. If the twins have the same DNA markers, they are most likely monozygotic. If they have different markers, they are dizygotic.

The genetic similarities in the DNA of monozygotic twins explain why they look remarkably similar and can even share similar traits, interests, behaviors, and personalities. Monozygotic twins will also have the same blood type.

Sometimes, zygosity can be determined during pregnancy, but it depends on the timing of the split. Some monozygotic twins develop with a single, shared placenta and are enclosed in a single chorion or amnion. Healthcare providers can look for these telltale signs on an ultrasound, but it's not definitive of monozygotic twins.

Amniocentesis can also be used to determine twin zygosity before birth, but it is an invasive procedure and is not generally part of routine prenatal care.

There is some research looking into using less-invasive prenatal DNA testing to determine twin zygosity. Talk to your OBGYN or your child's pediatrician about DNA testing options.

Your twins are probably not monozygotic/identical if...

• They are boy/girl twins
• They have different blood types
• They look very different

Your twins might be monozygotic/identical if...

• They are the same sex and look very similar
• They shared one placenta

Your twins are monozygotic/identical if...

• DNA testing confirms they are identical
• They shared one amniotic sac

"Identical" Twins Are Individuals

DNA tests can be used to compare the twins' genetic markers and confirm that they are monozygotic. However, genetics do not determine everything about a person. For example, research has shown that monozygotic twins do not necessarily have the same genetic risk factors for disease.

Furthermore, identical twins do not have the same fingerprints. While the patterns are similar, they are not exactly alike. A set of identical twins is still made up of two separate people. Environmental influences, epigenetic differences, and life experiences make each twin a unique individual.

Can two different sperm form twins?

Can you have twins with one egg and two sperm?

What happens if two different sperm fertilize the same egg?

How is identical twins formed?