Progress Educational Trust conference: What do we know about twins?

Twins have long been an endless source of fascination to their family, friends and society, and also to scientists. This year, the topics of twins in genetics and twins in fertility treatment formed the two halves of Progress Educational Trust's annual conference, held at the Institute of Child Health, University College London (UCL) on 4 December. The first session, 'What do we know about twins' was ably chaired by Professor John Galloway, a Trustee of PET and, appropriately enough, a father of twins. A show of hands revealed that many of the audience members were also parents of twins or twins themselves, joining a diverse mix of scientists, obstetricians, fertility healthcare professionals, journalists, policymakers and students.

The session began with a presentation by George Attikalos, consultant in fetal medicine and obstetrics at UCL. He started with a quiz: if twins share one placenta, are they monozygotic (identical) or dizygotic (non-identical)? Most of the audience correctly answered that if there's only one placenta then the twins must have arisen from a single fertilised egg that split into two - so they are monozygotic. However, many were uncertain about the follow-up question: what if they each have a placenta? The answer is they could be either identical or non-identical: such pregnancies can either arise from two different fertilised eggs (dizygotic), or a single fertilised egg that splits before the placental tissue has started to form (monozygotic).

Why does the number of placentas (the chorionicity) in a twin pregnancy matter? If twins share a placenta then there is an increased risk of complications, notably twin-to-twin transfusion syndrome (TTTS). In pregnancies affected by this condition, one twin has a placenta with a more extensive blood supply than the other, so grows faster and bigger than the other twin. Left untreated, there is a high risk of losing either one or both. Women carrying such a pregnancy will therefore be offered scans once every two weeks, rather than the usual four weeks recommended for twins. If TTTS is detected early, it can be successfully treated in the womb using a camera and laser, as George showed in a remarkable video of the procedure. It seems that smartphones can play a vital role in establishing chorionicity, with early scan photos taken by partners offering a much better view than scans carried out after 13-14 weeks!

The second talk saw Dr Jane Hurst, lead consultant and clinician in clinical genetics at Great Ormond Street Hospital, explain how 'identical twins can be different and non-identical twins similar'. She started with some figures: in the UK, the incidence of twin births has risen sharply from 9.6 per 1000 in 1980, to 16.1 per 1000 in 2009. Around 30 percent of this increase can be accounted for by the rise in older mothers, since the chances of having twins jumps from two percent for women under 25, to seven percent for the over-40s.

Jane went on to describe how identical twins can be different genetically, despite being the result of the fertilisation of a single egg by a single sperm. Genetic mutations can sometimes arise in a single cell of the very early embryo. In a singleton pregnancy, this would lead to a condition known as mosaicism, in which the cells of the body of a single person can have a different genetic make-up. If, however, it happens in an embryo that then splits into two, the result is twins who are not completely genetically identical. This rare occurrence is generally only detected when a mutation arises that causes a genetic condition in one twin but not the other.

Another genetic process that can explain ill health in one identical female twin and not the other is non-random X-inactivation, which can cause X-linked genetic diseases such as Duchenne muscular dystrophy, which usually only affects boys. Conversely, non-identical twins can be more alike than ordinary siblings. This can happen because although dizygotic twins only share half their genes, they also share a womb, so are equally affected by factors such as maternal illness and a simple lack of space.

Sir John Burn, professor of clinical genetics at Newcastle University's Institute of Genetic Medicine, closed the first session with a fascinating account of his research into twinning and heart malformations. The project began with the observation that monozygotic twins are almost three times more likely to have a heart defect than singletons. These conditions occur in 6/1000 singleton, 11/1000 twin and 17/1000 monozygotic twin pregnancies. What's more, 'identical' twins are often discordant: that is, one may have a heart defect while the other is unaffected. John described the case of twins that both had a particular genetic mutation known to cause a type of heart defect called tetralogy of Fallot, yet only one was affected. One possible explanation for this situation is different placental blood supplies, due to TTTS — meaning that the smaller twin is more susceptible to the harmful effects of the mutation.

Another possible explanation for differences in heart problems between identical twins could be disruption of the signals that specify the 'left-right' axis of the developing early embryo. These molecules work by spreading from the left to the right, so if the embryo splits while this crucial process is occurring it may have serious consequences for the 'right-hand twin'. John concluded his talk by stating that his findings show that twin heritability estimates (a measure of the proportion of the observed differences for a disease that are due to genetic variation) are meaningless, at least for heart malformations.

Following the talks, the audience asked the panel a wide range of insightful and interesting questions, making for one of the lively discussions that has become a defining highlight of PET conferences. Summing up, chair John Galloway commented that 'twinliness' was a rich and interesting subject, with far more to it than the simple distinction between identical and non-identical twins.

PET is grateful to the conference's sponsors Merck Serono, the London Women's Clinic, Ferring  Pharmaceuticals and the Medical Research Council.

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