Twin

Adult fraternal twins

Despite being dizygotic (fraternal) twins, Naomi (left) and Lisa-Kaindé Diaz share similar looks.

Two fraternal twin brothers have commonalities.

Dizygotic (DZ) or fraternal twins (also referred to as "non-identical twins", "dissimilar twins", "biovular twins", and, informally in the case of females, "sororal twins") usually occur when two fertilized eggs are implanted in the uterus wall at the same time. When two eggs are independently fertilized by two different sperm cells, fraternal twins result. The two eggs, or ova, form two zygotes, hence the terms dizygotic and biovular. Fraternal twins are, essentially, two ordinary siblings who happen to develop in the womb together and who are born at the same time, since they arise from two separate eggs fertilized by two separate sperm, just like ordinary siblings. This is the most common type of twin.[20]

Dizygotic twins, like any other siblings, will practically always have different sequences on each chromosome, due to chromosomal crossover during meiosis. Dizygotic twins share only 50 percent of each other's genes, which resemble amongst siblings that are conceived and born at different times. Like any other siblings, dizygotic twins may look similar, particularly as they are the same age. However, dizygotic twins may also look very different from each other (for example, be of opposite sexes).

Studies show that there is a genetic proclivity for dizygotic twinning. However, it is only the mother who has any effect on the chances of having such twins; there is no known mechanism for a father to cause the release of more than one ovum. Dizygotic twinning ranges from six per thousand births in Japan (similar to the rate of monozygotic twins) to 14 and more per thousand in some African countries.[21]

Dizygotic twins are also more common for older mothers, with twinning rates doubling in mothers over the age of 35.[22] With the advent of technologies and techniques to assist women in getting pregnant, the rate of fraternals has increased markedly.

Monozygotic (MZ) or identical twins occur when a single egg is fertilized to form one zygote (hence, "monozygotic") which then divides into two separate embryos. The chances of having identical twins is relatively rare — around 3 or 4 in every 1,000 births.[23]

Regarding spontaneous or natural monozygotic twinning, a recent theory proposes that monozygotic twins are probably formed when a blastocyst contains two inner cell masses (ICM), each of which will lead to a separate fetus, rather than by the embryo splitting while hatching from the zona pellucida (the gelatinous protective coating around the blastocyst).[24]

Monozygotic twins may also be created artificially by embryo splitting. It can be used as an expansion of in vitro fertilization (IVF) to increase the number of available embryos for embryo transfer.[25]

Monozygotic twinning occurs in birthing at a rate of about 3 in every 1000 deliveries worldwide (about 0.3% of the world population).[26]

The likelihood of a single fertilization resulting in monozygotic twins is uniformly distributed in all populations around the world.[22] This is in marked contrast to dizygotic twinning, which ranges from about six per thousand births in Japan (almost similar to the rate of identical twins, which is around 4–5) to 15 and more per thousand in some parts of India[27] and up to over 20 in some Central African countries.[11] The exact cause for the splitting of a zygote or embryo is unknown.

IVF techniques are more likely to create dizygotic twins. For IVF deliveries, there are nearly 21 pairs of twins for every 1,000.[28]

Comparison of zygote development in monozygotic and dizygotic twins. In the uterus, a majority of monozygotic twins (60–70%) share the same placenta but have separate amniotic sacs. In 18–30% of monozygotic twins each fetus has a separate placenta and a separate amniotic sac. A small number (1–2%) of monozygotic twins share the same placenta and amniotic sac. Fraternal twins each have their own placenta and own amniotic sac.

Monozygotic twins are genetically nearly identical and they are always the same sex unless there has been a mutation during development. The children of monozygotic twins test genetically as half-siblings (or full siblings, if a pair of monozygotic twins reproduces with another pair or with the same person), rather than first cousins. Identical twins do not have the same fingerprints however, because even within the confines of the womb, the fetuses touch different parts of their environment, giving rise to small variations in their corresponding prints and thus making them unique.[29]

Monozygotic twins always have the same genotype. Normally due to an environmental factor or the deactivation of different X chromosomes in female monozygotic twins, and in some extremely rare cases, due to aneuploidy, twins may express different sexual phenotypes, normally from an XXY Klinefelter syndrome zygote splitting unevenly.[30][31][32]

Monozygotic twins, although genetically very similar, are not genetically exactly the same. The DNA in white blood cells of 66 pairs of monozygotic twins was analyzed for 506,786 single-nucleotide polymorphisms known to occur in human populations. Polymorphisms appeared in 2 of the 33 million comparisons, leading the researchers to extrapolate that the blood cells of monozygotic twins may have on the order of one DNA-sequence difference for every 12 million nucleotides, which would imply hundreds of differences across the entire genome.[33] The mutations producing the differences detected in this study would have occurred during embryonic cell-division (after the point of fertilization). If they occur early in fetal development, they will be present in a very large proportion of body cells.

Another cause of difference between monozygotic twins is epigenetic modification, caused by differing environmental influences throughout their lives. Epigenetics refers to the level of activity of any particular gene. A gene may become switched on, switched off, or could become partially switched on or off in an individual. This epigenetic modification is triggered by environmental events. Monozygotic twins can have markedly different epigenetic profiles. A study of 80 pairs of monozygotic twins ranging in age from three to 74 showed that the youngest twins have relatively few epigenetic differences. The number of epigenetic differences increases with age. Fifty-year-old twins had over three times the epigenetic difference of three-year-old twins. Twins who had spent their lives apart (such as those adopted by two different sets of parents at birth) had the greatest difference.[34] However, certain characteristics become more alike as twins age, such as IQ and personality.[35][36][37]

In January 2021, new research from a team of researchers in Iceland was published in the journal Nature Genetics suggesting that identical twins may not be quite as identical as previously thought. The four-year study of monozygotic (identical) twins and their extended families revealed that these twins have genetic differences that begin in the early stages of embryonic development.[38]

A 1981 study of a deceased triploid XXX twin fetus without a heart showed that although its fetal development suggested that it was an identical twin, as it shared a placenta with its healthy twin, tests revealed that it was probably a polar body twin. The authors were unable to predict whether a healthy fetus could result from a polar body twinning.[39] However, a study in 2012 found that it is possible for a polar body to result in a healthy fetus.[40]

In 2003, a study argued that many cases of triploidy arise from sesquizygotic (semi-identical) twinning.[41]

See Semi-identical (sesquizygotic) twins below, under Unusual twinnings.

A pair of female ere ibeji twin figures (early 20th-century) in the permanent collection of The Children's Museum of Indianapolis. The Yoruba people have the highest dizygotic twinning rate in the world.

About 1 in 90 human births (1.1%) results from a twin pregnancy.[51] The rate of dizygotic twinning varies greatly among ethnic groups, ranging as high as about 45 per 1000 births (4.5%) for the Yoruba to 10% for Linha São Pedro, a tiny Brazilian settlement which belongs to the city of Cândido Godói.[52] In Cândido Godói, one in five pregnancies has resulted in twins.[53] The Argentine historian Jorge Camarasa has put forward the theory that experiments of the Nazi doctor Josef Mengele could be responsible for the high ratio of twins in the area. His theory was rejected by Brazilian scientists who had studied twins living in Linha São Pedro; they suggested genetic factors within that community as a more likely explanation.[54] A high twinning rate has also been observed in other places of the world, including:

• Igbo-Ora in Nigeria[55]
• Kodinhi, located in Kerala, India[56]
• Mohammadpur Umri, located in Uttar Pradesh, India[57][58][59]

The widespread use of fertility drugs causing hyperovulation (stimulated release of multiple eggs by the mother) has caused what some call an "epidemic of multiple births". In 2001, for the first time ever in the US, the twinning rate exceeded 3% of all births. Nevertheless, the rate of monozygotic twins remains at about 1 in 333 across the globe.

In a study on the maternity records of 5750 Hausa women living in the Savannah zone of Nigeria, there were 40 twins and 2 triplets per 1000 births. Twenty-six percent of twins were monozygotic. The incidence of multiple births, which was about five times higher than that observed in any western population, was significantly lower than that of other ethnic groups, who live in the hot and humid climate of the southern part of the country. The incidence of multiple births was related to maternal age but did not bear any association to the climate or prevalence of malaria.[60][61]

Twins are more common in people of African descent.[62]

The predisposing factors of monozygotic twinning are unknown.

Dizygotic twin pregnancies are slightly more likely when the following factors are present in the woman:

• She is of West African descent (especially Yoruba)
• She is between the age of 30 and 40 years
• She is greater than average height and weight
• She has had several previous pregnancies.

Women undergoing certain fertility treatments may have a greater chance of dizygotic multiple births. In the United States it has been estimated that by 2011 36% of twin births resulted from conception by assisted reproductive technology.[63]

The risk of twin birth can vary depending on what types of fertility treatments are used. With in vitro fertilisation (IVF), this is primarily due to the insertion of multiple embryos into the uterus. Ovarian hyperstimulation without IVF has a very high risk of multiple birth. Reversal of anovulation with clomifene (trade names including Clomid) has a relatively less but yet significant risk of multiple pregnancy.

Researchers suspect that as many as 1 in 8 pregnancies start out as multiples, but only a single fetus is brought to full term, because the other fetus has died very early in the pregnancy and has not been detected or recorded.[67] Early obstetric ultrasonography exams sometimes reveal an "extra" fetus, which fails to develop and instead disintegrates and vanishes in the uterus. There are several reasons for the "vanishing" fetus, including it being embodied or absorbed by the other fetus, placenta or the mother. This is known as vanishing twin syndrome. Also, in an unknown proportion of cases, two zygotes may fuse soon after fertilization, resulting in a single chimeric embryo, and, later, fetus.

Chang and Eng Bunker, born in Siam (now Thailand) in 1811, were the origin of the term "Siamese twins".

Conjoined twins (or the once-commonly used term "siamese") are monozygotic twins whose bodies are joined together during pregnancy. This occurs when the zygote starts to split after day 12[43] following fertilization and fails to separate completely. This condition occurs in about 1 in 50,000 human pregnancies. Most conjoined twins are now evaluated for surgery to attempt to separate them into separate functional bodies. The degree of difficulty rises if a vital organ or structure is shared between twins, such as the brain, heart, liver or lungs.

A chimera is an ordinary person or animal except that some of their parts actually came from their twin or from the mother. A chimera may arise either from monozygotic twin fetuses (where it would be impossible to detect), or from dizygotic fetuses, which can be identified by chromosomal comparisons from various parts of the body. The number of cells derived from each fetus can vary from one part of the body to another, and often leads to characteristic mosaicism skin coloration in human chimeras. A chimera may be intersex, composed of cells from a male twin and a female twin. In one case DNA tests determined that a woman, Lydia Fairchild, mystifyingly, was not the mother of two of her three children; she was found to be a chimera, and the two children were conceived from eggs derived from cells of their mother's twin.[68]

Sometimes one twin fetus will fail to develop completely and continue to cause problems for its surviving twin. One fetus acts as a parasite towards the other. Sometimes the parasitic twin becomes an almost indistinguishable part of the other, and sometimes this needs to be treated medically.

A very rare type of parasitic twinning is one where a single viable twin is endangered when the other zygote becomes cancerous, or "molar". This means that the molar zygote's cellular division continues unchecked, resulting in a cancerous growth that overtakes the viable fetus. Typically, this results when one twin has either triploidy or complete paternal uniparental disomy, resulting in little or no fetus and a cancerous, overgrown placenta, resembling a bunch of grapes.

Occasionally, a woman will suffer a miscarriage early in pregnancy, yet the pregnancy will continue; one twin was miscarried but the other was able to be carried to term. This occurrence is similar to the vanishing twin syndrome, but typically occurs later, as the twin is not reabsorbed.

It is very common for twins to be born at a low birth weight. More than half of twins are born weighing less than 5.5 pounds (2.5 kg), while the average birth weight of a healthy baby should be around 6–8 pounds (3–4 kg).[69] This is largely due to the fact that twins are typically born premature. Premature birth and low birth weights, especially when under 3.5 pounds (1.6 kg), can increase the risk of several health-related issues, such as vision and hearing loss, mental disabilities, and cerebral palsy.[70] There is an increased possibility of potential complications as the birth weight of the baby decreases.

Twin-to-twin transfusion syndrome (TTTS) illustration of twins showing one fetus with exposure to more amniotic fluid while the other is "stuck" with the membrane tightly around itself.

Monozygotic twins who share a placenta can develop twin-to-twin transfusion syndrome. This condition means that blood from one twin is being diverted into the other twin. One twin, the 'donor' twin, is small and anemic, the other, the 'recipient' twin, is large and polycythemic. The lives of both twins are endangered by this condition.

Stillbirths occurs when a fetus dies after 20 weeks of gestation. There are two types of stillbirth, including intrauterine death and intrapartum death. Intrauterine death occurs when a baby dies during late pregnancy. Intrapartum death, which is more common, occurs when a baby dies while the mother is giving birth. The cause of stillbirth is often unknown, but the rate of babies who are stillborn is higher in twins and multiple births. Caesareans or inductions are advised after 38 weeks of pregnancy for twins, because the risk of stillbirth increases after this time.[71]

Heterotopic pregnancy is an exceedingly rare type of dizygotic twinning in which one twin implants in the uterus as normal and the other remains in the fallopian tube as an ectopic pregnancy. Ectopic pregnancies must be resolved because they can be life-threatening to the mother. However, in most cases, the intrauterine pregnancy can be salvaged.

This phenomenon is known as heteropaternal superfecundation. One 1992 study estimates that the frequency of heteropaternal superfecundation among dizygotic twins, whose parents were involved in paternity suits, was approximately 2.4%; see the references section, below, for more details.

Dizygotic twins from biracial couples can sometimes be mixed twins, which exhibit differing ethnic and racial features. One such pairing was born in London in 1993 to a white mother and Caribbean father.[78]

Among monozygotic twins, in extremely rare cases, twins have been born with different sexes (one male, one female).[79] When monozygotic twins are born with different sexes it is because of chromosomal defects. The probability of this is so small that multiples having different sexes is universally accepted as a sound basis for in utero clinical determination that the multiples are not monozygotic.

Another abnormality that can result in monozygotic twins of different sexes is if the egg is fertilized by a male sperm but during cell division only the X chromosome is duplicated. This results in one normal male (XY) and one female with Turner syndrome (45,X).[80] In these cases, although the twins did form from the same fertilized egg, it is incorrect to refer to them as genetically identical, since they have different karyotypes.

Monozygotic twins can develop differently, due to their genes being differently activated.[81] More unusual are "semi-identical twins", also known as "sesquizygotic". As of 2019, only two cases have been reported.[82][83] These "half-identical twins" are hypothesized to occur when an unfertilized egg cleaves into two identical attached ova, both of which are viable for fertilization. Both ova are then fertilized, each by a different sperm, and the coalesced zygotes undergo further cell duplications developing as a chimeric blastomere. If this blastomere then undergoes a twinning event, two embryos will be formed, with different paternal genetic information and identical maternal genetic information.

This results in a set of twins with identical gene sequence from the mother's side, but different sequences from the father's side. Cells in each fetus carry chromosomes from either sperm, resulting in chimeras. This form had been speculated until only recently being recorded.[84][85][86]

Twin calves of the Hereford breed in Miles City, Montana

In 2007, a study reported a case of a pair of living twins, which shared an identical set of maternal chromosomes, while each having a distinct set of paternal chromosomes, albeit from the same man, and thus they most likely share half of their father's genetic makeup. The twins were both found to be chimeras. One was an intersex XX, and one a XY male. The exact mechanism of fertilization could not be determined but the study stated that it was unlikely to be a case of polar body twinning.[84][87]

In 2019, a second case of sesquizygotic twins was reported and molecular evidence of the phenomenon was documented by Gabbett and Fisk.[82] In this case, the twins shared 100% of their maternal chromosomes and 78% of their paternal genomic information. The authors postulate two sperm from the same man fertilized an ovum simultaneously. The chromosomes assorted themselves through heterogonesis to form three cell lines. The purely paternal cell line died out due to genomic imprinting lethality, while the other two cell lines, each conisiting of the same maternal DNA but only 50% identical paternal DNA, formed a morula which subsequently split into twins [82][88]

Mirror image twins result when a fertilized egg splits later in the embryonic stage than normal timing, around day 9–12. This type of twinning could exhibit characteristics with reversed asymmetry, such as opposite dominant handedness, dental structure, or even organs (situs inversus).[89] If the split occurs later than this time period, the twins risk being conjoined. There is no DNA-based zygosity test that can determine if twins are indeed mirror image.[90] The term "mirror image" is used because the twins, when facing each other, appear as matching reflections.[91]