Twin

Monozygotic ("identical") twins

A twin is one of two offspring produced in the same pregnancy.^[1] Twins can either be monozygotic (in common parlance, "identical"), meaning that they develop from one zygote that splits and forms two embryos, or dizygotic ("fraternal") because they develop from two separate eggs that are fertilized by two separate sperm.

In contrast, a fetus which develops alone in the womb is called a singleton, and the general term for one offspring of a multiple birth is multiple. It is theoretically possible for two singletons to be identical if all 23 chromosomes in both gametes from the mother and father were to be exact matches from one birth to the next. While this is statistically improbable (less than one in one billion-billion-billion chance) under natural conditions, a controlled pairing may someday be possible.

Statistics

The twin birth rate in the United States is almost 16 twin sets (or 32 twins) per 1,000 live births,^[2] while the Yoruba have the highest rate of twinning in the world, at 45-50 twin sets (or 90-100 twins) per 1,000 live births,^[3]^[4]^[5] possibly because of high consumption of a specific type of yam containing a natural phytoestrogen which may stimulate the ovaries to release an egg from each side.^[6]^[7]

The world's highest rates of twinning are found across Central Africa, where there are 18-30 twin sets (or 37-62 twins) per 1,000 live births.^[8] In Latin-America and South Asia and South-East Asia the lowest rates are found; only 6-9 twin sets per 1,000 live births. North-America and Europe have intermediate rates of 9–16 twin sets per 1,000 live births.^[8]

Due to the limited size of the mother's womb, multiple pregnancies are much less likely to carry to full term than single births, with twin pregnancies lasting only 37 weeks (3 weeks less than full term) on average.^[9]

Families with Twins have a higher chance of producing more twins than families without twins.

Zygosity

Zygosity is the degree of identity in the genome of twins. There are five common variations of twinning. The three most common variations are all dizygotic (fraternal):

Male–female twins are the most common result, 50 percent of dizygotic twins and the most common grouping of twins.
Female–female dizygotic twins (sometimes called "sororal twins")
Male–male dizygotic twins

The other two variations are monozygotic ("identical") twins:

Female–female monozygotic twins
Male–male monozygotic twins (least common)
Male-female "monozygotic" twins are possible, but exceedingly rare (but see below)

Among non-twin births, male singletons are slightly (about five percent) more common than female singletons. The rates for singletons vary slightly by country. For example, the sex ratio of birth in the US is 1.05 males/female,^[10] while it is 1.07 males/female in Italy.^[11] However, males are also more susceptible than females to death in utero, and since the death rate in utero is higher for twins, it leads to female twins being more common than male twins.

Fraternal/Sororal (dizygotic) twins

Eight-month-old sororal twin girls napping

Fraternal or dizygotic (DZ) twins (also referred to as "non-identical twins", "dissimilar twins", "biovular twins", and, in cases 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.

Dizygotic twins, like any other siblings, have an extremely small chance of having the same chromosome profile. Like any other siblings, dizygotic twins may look similar, particularly given that they are the same age. However, dizygotic twins may also look very different from each other. They may be of different sexes or the same sex. The same holds true for brothers and sisters from the same parents, meaning that fraternal and/or sororal twins are simply siblings who happen to be the same age.

Studies show that there is a genetic basis for dizygotic twinning. However, it is only their mother that 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.^[6]

Dizygotic twins are also more common for older mothers, with twinning rates doubling in mothers over the age of 35.^[12] With the advent of technologies and techniques to assist women in getting pregnant, the rate of fraternals has increased markedly.

Monozygotic ("identical") twins

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 (MZ) or identical twins occur when a single egg is fertilized to form one zygote (hence, "monozygotic") which then divides into two separate embryos.

Mechanism

Regarding spontaneous or natural monozygotic twinning, a recent theory posits that monozygotic twins are formed after a blastocyst essentially collapses, splitting the progenitor cells (those that contain the body's fundamental genetic material) in half, leaving the same genetic material divided in two on opposite sides of the embryo. Eventually, two separate fetuses develop.^[13] Spontaneous division of the zygote into two embryos is not considered to be a hereditary trait, but rather a spontaneous or random event.^[12]^[14]

Monozygotic twins may also be created artificially by embryo splitting. It can be used as an expansion of IVF to increase the number of available embryos for embryo transfer.^[15]

Incidence

Monozygotic twinning occurs in birthing at a rate of about three in every 1000 deliveries worldwide.^[14]

The likelihood of a single fertilization resulting in monozygotic twins is uniformly distributed in all populations around the world.^[12] 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^[16] and up to over 20 in some Central African countries.^[8] The exact cause for the splitting of a zygote or embryo is unknown.

In-vitro fertilization techniques are more likely to create dizygotic twins. Only about three pairs of twins per 1,000 deliveries occur as a result of natural conception, while for IVF deliveries, there are nearly 21 pairs of twins for every 1,000.^[17]

Genetic and epigenetic similarity

Monozygotic twins are genetically identical and they are always the same sex unless there has been a mutation during development. The children of monozygotic twins test as half-siblings (or full siblings, if monozygotic twin sisters reproduce with monozygotic twin brothers), rather than first cousins. On rare occasions, monozygotic twins may express different phenotypes, 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's syndrome zygote splitting unevenly.^[18]^[19]

Monozygotic twins actually have only nearly identical DNA, and differing environmental influences throughout their lives affect which genes are switched on or off. This is called epigenetic modification. A study of 80 pairs of human twins ranging in age from three to 74 showed that the youngest twins have relatively few epigenetic differences. The number of epigenetic differences between "identical" twins 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.^[20] However, certain characteristics become more alike as twins age, such as IQ and personality. This phenomenon illustrates the influence of genetics in many aspects of human characteristics and behavior.^[21]^[22]^[23]

Phenotype similarity

Contrary to common opinion, monozygotic twins are not always of the same phenotypical sex. There have been described cases where monozygocity resulted in 46,XO (i.e. female with Turner syndrome) and 46,XY (i.e. male). This is thought to be due to unequal distribution of zygotic protoplasm. However, as a rule, traits and physical appearances of MZ twins are very similar.

Monozygotic twins do generally look alike, although they do not have the same fingerprints (which are environmental as well as genetic). As they mature, monozygotic twins often look less alike or more alike because of lifestyle choices or external influences.

Semi-identical twins

Half-identical or semi-identical twins (also referred to as "half twins") are the result of a very rare form of twinning in which the twins inherit exactly the same genes from their mother but different genes from their father. Although examples of half-identical twins have been found, the exact mechanism of their conception is not well-understood, but could theoretically occur in polar body twinning where sperm cells fertilize both the ovum and the second polar body.

This situation is not the same as the common form of fraternal twinning, in which two genetically different ova are fertilized by two genetically different sperm. In this case, the ova are genetically identical.

Types

There are two mechanisms by which this might happen:

Polar twins (or "polar body twins"), where two sperm fertilize an ovum, one of the two fertilizing a polar body;^[24] or where an ovum splits into identical copies, one containing a polar body, prior to fertilization, allowing it to be fertilized by two different sperm.^[25]^[26]
Sesquizygotic twins, where two sperm fertilize the one ovum, forming a triploid, and then splitting.^[27]

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 likely a polar body twin. The authors were unable to predict whether a healthy fetus could result from a polar body twinning.^[28] In 2003 a study argued that many cases of triploidity arise from semi-identical twinning.^[29] In 2007, a study reported a case of a pair of living twins, one a hermaphrodite and one a phenotypical male. The twins were both found to be chimeras and to share all of their maternal DNA but only half of their father's DNA. 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.^[30]

Degree of separation

Various types of chorionicity and amniosity (how the baby's sac looks) in monozygotic (one egg/identical) twins as a result of when the fertilized egg divides

The degree of separation of the twins in utero depends on if and when they split into two zygotes. Dizygotic twins were always two zygotes. Monozygotic twins split into two zygotes at some time very early in the pregnancy. The timing of this separation determines the chorionicity and amniocity (the number of sacs) of the pregnancy. Dichorionic twins either never divided (i.e.: were dizygotic) or they divided within the first 4 days. Monoamnionic twins divide after the first week.

In very rare cases, twins become conjoined twins. Furthermore, there can be various degrees of shared environment of twins in the womb, potentially leading to pregnancy complications.

It is a common misconception that two placentas means twins are dizygotic. But if monozygotic twins separate early enough, the arrangement of sacs and placentas in utero is indistinguishable from dizygotic twins.

Type	Description	Day
Dichorionic-Diamniotic	Normally, twins have two separate (di- being a numerical prefix for two) chorions and amniotic sacs, termed Dichorionic-Diamniotic or "DiDi". It occurs in almost all cases of dizygotic twins (except in very rare cases of fusion between their blastocysts^[31] ), in 99.7% of all pregnancies,^[32] and in 18–36%^[33] (or around 25%^[31]) of monozygotic (identical) twins. DiDi twins have the lowest mortality risk at about 9 percent, although that is still significantly higher than that of singletons.^[34]	Dichorionic-Diamniotic twins form when splitting takes place by the third day after fertilization.^[31]
Monochorionic-Diamniotic	Monochorionic twins share the same placenta. Monochorionic twins generally have two amniotic sacs (called Monochorionic-Diamniotic "MoDi"), which occurs in 60–70% of the pregnancies with monozygotic twins.^[33] Monochorionic-Diamniotic twins are almost always monozygotic, with a few exceptions where the blastocysts have fused.^[31]	Days 4-8
Monochorionic-Monoamniotic	When the division of the developing zygote into 2 embryos occurs, 99% of the time it is within 8 days of fertilization Sometimes, monochorionic twins also share the same amnion. This situation occurs in 1–2% of monozygotic twin pregnancies.^[33] Monoamniotic twins are always monozygotic.^[35] The survival rate for monoamniotic twins is somewhere between 50%^[35] to 60%.^[36] Consequently, if twins are monoamniotic that means that the two babies will be sharing a placenta and as a result, due to the small capacity of sharing a sac, the umbilical cord has an increased chance of being tangled around the babies. Because of this, there is an increased chance that the newborns may be miscarried or suffer from cerebral palsy due to the lack of oxygen.	Monoamniotic twins occur when the split takes place after the ninth day after fertilization.^[31]
Conjoined twins	When the division of the developing zygote into 2 embryos occurs, 99% of the time it is within 8 days of fertilization. Mortality is highest for conjoined twins due to the many complications resulting from shared organs.	If the division of the zygote occurs later than the 12 days then conjoined twins are usually the result.

Demographics

A recent study has found that insulin-like growth factor present in dairy products may increase the chance of dizygotic twinning. Specifically, the study found that vegan mothers (who exclude dairy from their diets) are one-fifth as likely to have twins as vegetarian or omnivore mothers, and concluded that "Genotypes favoring elevated IGF and diets including dairy products, especially in areas where growth hormone is given to cattle, appear to enhance the chances of multiple pregnancies due to ovarian stimulation."^[37]

From 1980–97, the number of twin births in the United States rose 52%.^[38] This rise can at least partly be attributed to the increasing popularity of fertility drugs like Clomid and procedures such as in vitro fertilization, which result in multiple births more frequently than unassisted fertilizations do. It may also be linked to the increase of growth hormones in food.^[37]

Ethnicity

About 1 in 90 human births (1.1%) results from a twin pregnancy.^[39] The rate of dizygotic twinning varies greatly among ethnic groups, ranging as high as about 45 per 1000 births for the Yoruba to 10% for Linha São Pedro, a tiny Brazilian settlement which belongs to the city of Cândido Godói.^[40] In Cândido Godói, one in five pregnancies have resulted in twins.^[41] The Argentine historian Jorge Camarasa has put forward a theory that experiments of the Nazi doctor Josef Mengele could be responsible for the high ratio of twins in the area.^[42] 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.^[43] A high twinning rate has also been observed in other places of the world, including Igbo-Ora in Nigeria^[44] and Kodinji in India.^[45]

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 monozygous. 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.^[46]

Predisposing factors

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. This can vary depending on what types of fertility treatments are used. With in vitro fertilization (IVF), this is primarily due to the insertion of multiple embryos into the uterus. Some other treatments such as the drug Clomid can stimulate a woman to release multiple eggs, increasing the likelihood of multiples.

Delivery interval

A 15-year German study^[47] of 8,220 vaginally delivered twins (that is, 4,110 pregnancies) in Hesse yielded a mean delivery time interval of 13.5 minutes.^[48] The delivery interval between the twins was measured as follows:

Within 15 minutes: 75.8%
16-30 minutes: 16.4%
31-45 minutes: 4.3%
46-60 minutes: 1.7%
Over 60 minutes: 1.8% (72 instances)

The study stated that the occurrence of complications "was found to be more likely with increasing twin-to-twin delivery time interval" and suggested that the interval be kept short, though it noted that the study did not examine causes of complications and did not control for factors such as the level of experience of the obstetrician, the wish of the women giving birth, or the "management strategies" of the procedure of delivering the second twin.

Complications of twin pregnancy

Vanishing twins

Main article: Vanishing twin

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 has died very early in the pregnancy and has not been detected or recorded.^[49] Early obstetric ultrasonography exams sometimes reveal an "extra" fetus, which fails to develop and instead disintegrates and vanishes. This is known as vanishing twin syndrome.

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

Conjoined twins

Main article: Conjoined twin

Conjoined twins (or the deprecated term "Siamese twins") are monozygotic twins whose bodies are joined together during pregnancy. This occurs where the single zygote of MZ twins fails to separate completely, and the zygote starts to split after day 12^[31] following fertilization. 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 or liver.

Chimerism

Main article: Chimera (genetics)

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.

Parasitic twins

Main article: Parasitic twin

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 medically dealt with.

Partial molar twins

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.

Miscarried twin

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 than the vanishing twin syndrome.

Low birth weight

Twins typically suffer from the lower birth weights and greater likelihood of prematurity that is more commonly associated with the higher multiple pregnancies.

Twin-to-twin transfusion syndrome

Main article: Twin-to-twin transfusion syndrome

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.

Human twin studies

Main article: Twin study

Jewish twins kept alive to be used in Mengele's medical experiments.

Twin studies are utilized in an attempt to determine how much of a particular trait is attributable to either genetics or environmental influence. These studies compare monozygotic and dizygotic twins for medical, genetic, or psychological characteristics to try to isolate genetic influence from epigenetic and environmental influence. Twins that have been separated early in life and raised in separate households are especially sought-after for these studies, which have been used widely in the exploration of human nature. However, the utility and accuracy of these twin studies has been called into question and remains controversial. Classical twin studies have are now being supplemented with molecular genetic studies which identify individual genes.

Unusual twinnings

Among dizygotic twins, in rare cases, the eggs are fertilized at different times with two or more acts of sexual intercourse, either within one menstrual cycle (superfecundation) or, even more rarely, later on in the pregnancy (superfetation). This can lead to the possibility of a woman carrying fraternal twins with different fathers (that is, half-siblings). 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 Germany in 2008 to a white father from Germany and a black mother from Ghana.^[50]

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.

Among monozygotic twins, in extremely rare cases, twins have been born with different sexes (one male, one female). The probability of this is so vanishingly small (only 3 documented cases^[51]) that multiples having different sexes is universally accepted as a sound basis for a clinical determination that in utero multiples are not monozygotic. When monozygotic twins are born with different sexes it is because of chromosomal birth defects. In this case, although the twins did come from the same egg, it is incorrect to refer to them as genetically identical, since they have different karyotypes.

Semi-identical twins

Monozygotic twins can develop differently, due to different genes being activated.^[52] More unusual are "semi-identical twins". These "half-identical twins" are hypothesized to occur when an unfertilized egg cleaves into two identical attached ova and which are viable for fertilization. Both cloned ova are then fertilized by different sperm and the coalesced eggs undergo further cell duplications developing as a chimeric blastomere. If this blastomere then undergoes a twinning event, two embryos will be formed, each of which have different paternal genes and identical maternal genes.

This results in a set of twins with identical genes from the mother's side, but different genes from the father's side. Cells in each fetus carry genes from either sperm, resulting in chimeras. This form had been speculated until only recently being recorded in western medicine.^[53]^[54]^[55]

Twin calves of the Hereford breed

Animal twins

Twins are common in many animal species, such as cats, sheep, ferrets and deer. The incidence of twinning among cattle is about 1–4%, and research is under way to improve the odds of twinning, which can be more profitable for the breeder if complications can be sidestepped or managed. A female calf that is the twin of a bull becomes partially masculinized and is known as a freemartin. The nine-banded armadillo (Dasypus novemcinctus) has identical twins (usually four babies) as its regular reproduction and not as exceptional cases.^[56]^[57]

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