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Tuesday 29 June 2021

Types of twins

Scientists are very interested in twins because it helps us identify the differences between genetic and environmental factors that influence health and behaviour. As a result, there’s been a lot of research on them, and this has uncovered some unusual types of twinning… such as sesquizygotic twins.

MultipleParent via Wikipedia Commons.
Most twins are monozygotic (identical: they come from a single egg that split in two), or dizygotic (non-identical or fraternal: they come from two eggs that were released by their mother at the same time); however, a third category has been identified: sesquizygotic, or in-between twins. Identical twins are almost 100% genetically identical (although scientists have revealed they still have some genetic differences[1]! We’re not sure why, but mapping these differences could tell us about exactly when the parent egg split into two). Fraternal twins have around 50% of their DNA in common, just like any pair of siblings. Sure, there is some variation, but it’s very unusual to have twins with much more than 50% of their DNA in common, but much less than 100%... But this is exactly what has been found in sesquizygotic or semi-identical twins. Scientists think there must be some kind of explanation. However, they are so rare (or so rarely identified), we just don’t have the data to investigate. And if they do come about through some other mechanism, what is it[2]?

One theory is dispermic fertilisation[3][4], where an egg is fertilised by two sperm, and then splits, so each sperm ends up in a different twin, but the two share an egg. However, it is more normal if an egg is doubly fertilised that a second set of genetic data persists – and, if this happens, the foetus or foetuses die.

Another theory is polar body fertilisation[5][6]. Polar bodies are basically made during mitosis (the process that makes egg and sperm cells) when cells split unevenly, creating one strong daughter cell (an egg), and one that doesn’t have enough nutrients in it to survive. Mostly, polar bodies disintegrate. However, sometimes they do survive and persist, and scientists think these may have the ability to be fertilised. Theoretically, you could get sesquizygotic twins from an egg and polar body if they were fertilised by two different sperm. However, since polar bodies are weak, scientists aren’t even sure if they have enough nutrients to develop into a living foetus.

However, fertilisation of this kind might explain chimeric twins, or when one twin “vanishes”. Of course, they don’t really vanish: their whole cells get absorbed by the living twin and incorporated into their body. Where the twins are fraternal, this leads to one person with two sets of DNA[3], with different cells differing in random parts of their body. We don’t know why these cells don’t recognise each other as foreign and attack each other (a potentially useful tool for organ transplant science), but it may have something to do with developing in the womb, and the placenta. In fact, chimerism amongst twins and even amongst siblings is common: cells from one twin can be found in another, or those from an older sibling can be found in a younger one[7]. Women can incorporate cells from their babies into their bodies too[8][9]. Some people even show “blood twinning”, where two distinct blood types are found[10]. In fraternal twins, this occurs around 8% of the time, and in triplets, in 21% of cases[11]!

Illustration of conjoined twins. Nuremberg Chronicle, by Hartmann Schedel (1440-1514) via Wikipedia Commons

twins may come about from a similar mechanism of absorption[12], but where both twins are still alive. And it could explain external heteropagus twins[13], where one is not fully developed and relies upon the other for survival. Scientists think this “fusion” could explain why most conjoined twins are attached at the chest and share a heart – one of the last organs to develop[14]. What look like extra limbs could actually be vestiges of an absorbed twin[15]: DNA tests have supposedly shown that these can sometimes have their own sets of DNA: just like a fraternal twin.

However, no one really knows why conjoinment happens, and it could be the result of incomplete splitting instead: the idea is that if the egg splits too late (after 2 weeks), it doesn’t fully manage it, resulting in the development of two humans that may share some organs. No one has actually seen an egg splitting, and we don’t know much about its mechanisms[16].

Conjoined twins show higher degrees of mirroring. This is a strange phenomenon in twins where identical twins look like mirror images of each other, and may even have situs inversus (organs on opposite sides)[17][12]! Complete mirroring is rare, but small amounts of mirroring in any pair of identical twins is common. Scientists think this might tell us when the egg split in half, with full mirror image twins resulting from a late split, and only slightly mirrored twins from an early one[18]. However, not all scientists agree that it is due to timing, and mirroring in twins remains mysterious.

An even weirder finding in foetuses is “fetus in fetu”, or one twin entirely inside another. Obviously, this does not lead to a second living foetus, but is estimated to happen in 1 in every half a million live births[19]! The internal twin (or more than one, as up to eleven have been reported in one foetus[20]!) may, however, not be an actual twin, but a teratoma: a type of tumour that forms into whole organs or tissues such as hair[21]! We don’t understand why these tumours happen and are usually benign (but not always[22]), but understanding more could help us in the battle against cancer. However, they seem to be more common in females and in babies, suggesting a connection with early development and rapid cell division.

why don't all references have links?

[1] Bruder, C. E., Piotrowski, A., Gijsbers, A. A., Andersson, R., Erickson, S., de Ståhl, T. D., ... & Dumanski, J. P. (2008). Phenotypically concordant and discordant monozygotic twins display different DNA copy-number-variation profiles. The American Journal of Human Genetics, 82(3), 763-771.
[2] Gabbett, Michael T., et al. Molecular support for heterogonesis resulting in sesquizygotic twinning. New England Journal of Medicine 380.9 (2019): 842-849.
[3] Giltay, J. C., Brunt, T., Beemer, F. A., Wit, J. M., Van Amstel, H. K. P., Pearson, P. L., & Wijmenga, C. (1998). Polymorphic detection of a parthenogenetic maternal and double paternal contribution to a 46, XX/46, XY hermaphrodite. The American Journal of Human Genetics, 62(4), 937-940.
[4] Golubovsky, M. (2006). Mosaic/chimeras and twinning in the current reproductive genetics perspective. Human Reproduction, 21(9), 2458-2460.
[5] Wakayama, T., & Yanagimachi, R. (1998). The first polar body can be used for the production of normal offspring in mice. Biology of reproduction, 59(1), 100-104.
[6] Fancsovits, P., Tóthné, Z. G., Murber, A., Takacs, F. Z., Papp, Z., & Urbancsek, J. (2006). Correlation between first polar body morphology and further embryo development. Acta Biologica Hungarica, 57(3), 331-338.
[7] Opstelten, R., Slot, M. C., Lardy, N. M., Lankester, A. C., Mulder, A., Claas, F. H., ... & Amsen, D. (2019). Determining the extent of maternal-foetal chimerism in cord blood. Scientific reports, 9(1), 1-10.
[8] Koopmans, M., Hovinga, I. C. K., Baelde, H. J., Harvey, M. S., de Heer, E., Bruijn, J. A., & Bajema, I. M. (2008). Chimerism occurs in thyroid, lung, skin and lymph nodes of women with sons. Journal of reproductive immunology, 78(1), 68-75.
[9] Kelly, S. E. (2012). The maternal–foetal interface and gestational chimerism: the emerging importance of chimeric bodies. Science as Culture, 21(2), 233-257.
[10] Booth, P. B., Plaut, G., James, J. D., Ikin, E. W., Moores, P., Sanger, R., & Race, R. R. (1957). Blood chimerism in a pair of twins. British medical journal, 1(5033), 1456.
[11] Van Dijk, B. A., Boomsma, D. I., & de Man, A. J. (1996). Blood group chimerism in human multiple births is not rare. American journal of medical genetics, 61(3), 264-268.
[12] Joyce, J. Cyril. "Dextrocardia, Situs Inversus, and Twinning." British medical journal 2.4945 (1955): 950.
[13] Sharma, G., Mobin, S. S. N., Lypka, M., & Urata, M. (2010). Heteropagus (parasitic) twins: a review. Journal of pediatric surgery, 45(12), 2454-2463.
[14] Mathew, Rishi Philip, et al. Conjoined twins–role of imaging and recent advances. Journal of ultrasonography 17.71 (2017): 259.
[15] Gul, A., Aslan, H., & Ceylan, Y. (2004). Prenatal diagnosis of pygopagus tetrapus parasitic twin: case report. BMC pregnancy and childbirth, 4(1), 1-7.
[16] Spencer, R. (1992). Conjoined twins: theoretical embryologic basis. Teratology, 45(6), 591-602.
[17] Newman, H. H. (1928). Studies of human twins: II. Asymmetry reversal, of mirror imaging in identical twins. The Biological Bulletin, 55(4), 298-315.
[18] Kaufman, M. H. (2004). The embryology of conjoined twins. Child's Nervous System, 20(8-9), 508-525.
[19] Thakral CL, Maji DC, Sajwani MJ. Fetus-in-fetu: a case report and review of the literature. J Pediatr Surg 1998; 33:1432–1434.
[20] Gerber, Rebecca E., et al. Fetus in fetu: 11 fetoid forms in a single fetus: review of the literature and imaging. Journal of Ultrasound in Medicine 27.9 (2008): 1381-1387.
[21] Higgins, Kimberly R., and Brian D. Coley. Fetus in fetu and fetaform teratoma in 2 neonates: an embryologic spectrum?. Journal of ultrasound in medicine 25.2 (2006): 259-263.
[22] Hopkins, Katharine L., et al. "Fetus-in-fetu with malignant recurrence." Journal of pediatric surgery 32.10 (1997): 1476-1479.

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