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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