Early Human Development 64 (2001) 105 117

www.elsevier.com/locate/earlhumdev

Mechanisms for differences in monozygous twins

Paul Gringrasa,*, Wai Chenb,c
a

The Multiple Births Foundation, Hammersmith House, Level 4, Queen Charlottes and Chelsea Hospital,
Du Cane Road, London W12 OHS, UK
b
Bloomfield Clinic, Department of Child and Adolescent Psychiatry, Guys, St. Thomass and Kings
School of Medicine, Guys Hospital, St. Thomas Street, London SE1 9RT, UK
c
Centre of Social, Genetic and Developmental Psychiatry Research, Institute of Psychiatry,
KCL London SE5, UK
Received 1 July 2000; received in revised form 23 March 2001; accepted 14 April 2001

Abstract
Monozygous (MZ) twins are often described as being physically and genetically identical.
Clinical determination of zygosity relies on the assumption that any physical differences between a
pair of twins imply they are dizygous. Most twin research relies on the assumption that dizygous
twins share approximately 50% of the same genes, whereas monozygous twins share 100%. There
is, however, increasing evidence to challenge both these assumptions. In this review, we describe a
number of intrauterine effects and genetic mechanisms that may result in phenotypic, genotypic, and
epigenetic differences between monozygous twins. Newer molecular techniques are resulting in
such differences being increasingly commonly recognised. The potential for differences in
monozygotic twin pairs is an important consideration for both clinicians and researchers involved in
twin work. D 2001 Elsevier Science Ireland Ltd. All rights reserved.
Keywords: Twin; Monozygous; Genetic mechanisms

1. Introduction
Over 200 pairs of twins are assessed each year at the Multiple Births Foundation,
London. Despite often appearing indistinguishable to strangers, no identical twins
assessed are so alike that their mothers fail to distinguish them accurately. Physical
differences may be as subtle as one small mole, or a differently positioned hair crown;
*

Corresponding author. Tel.: +44-208-383-3519.

E-mail address: paulg@pobox.com (P. Gringras).

0378-3782/01/$ see front matter D 2001 Elsevier Science Ireland Ltd. All rights reserved.
PII: S 0 3 7 8 - 3 7 8 2 ( 0 1 ) 0 0 1 7 1 - 2

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but still, they exist and are unmistakable once identified. Many parents can also
differentiate their identical twins by their personalities, some even claim from a very
early age.
Physical similarities between MZ twins are well recognised; and these similarities
have long formed the basis of many instruments and clinical methods designed to
classify zygosity, such as questionnaires and physical examinations. Even the most
experienced practitioners can, however, misclassify zygosity in about 6% of cases [1],
and molecular genetic methods are now the preferred method for establishing zygosity
[2]. The term identicalalthough frequently usedis not synonymous with monozygous (MZ).
Most MZ twins are phenotypically very similar, yet there are significant numbers of
MZ pairs who are neither phenotypically nor genotypically identical. Even if one
assumes a completely equal apportioning of genetic endowment when twinning occurs,
the twin pair will only remain identical if post-zygotic genetic, post-zygotic epi-genetic
and post-zygotic environmental factors affect each twin equally. Given the extent of
these influences and many potential opportunities for disruption during the long and
complex intrauterine development, it is perhaps surprising that so many MZ twins do
turn out to be so alike. Nevertheless, it is these anomalous cases of discordant twins that
have taught us much about human genetics, development and twinning in the past. It is
likely that they will continue to do so when new technologies are applied to future
research in this area. This review summarises some past findings of well established
studies, and also some from more recent exploratory studies using more experimental
techniques and designs.
We will first consider the ante-natal environmental factors and their effects, and then
the genetic factors that contribute to discordance in MZ twins. Some examples of
discordancy do not necessarily fit into the above neat categories. For convenience, they
have been grouped together and discussed in the final section on discordancies of
unknown origin.

2. Timing of monozygous twinning

Monozygous (MZ) twinning occurs when one single fertilised egg gives rise to two
separate embryos. The timing of this division can be an important contributory factor in
determining the post-zygotic discordance in MZ twins. This timing can be characterised by
the differences in amniotic sac, chorionic and placental anatomical formation [3]. In
principle, the earlier twinning occurs, the less the twins will share common supportive
structures; and the later, the more. The extreme example of late twinning are conjoint twins
who even share some somatic organs.
If twinning takes place prior to the first 4 days after conception, two separate placentas
and sets of membranes are formed: that is, one set for each embryo. Such twins are called
dichorionic (DC) MZ twins, and they account for about one third of all MZ twins.
After the fourth day, the progenitor cells of the placenta become separated from the
inner cell mass of the embryo. As a result, for twinning occurring after this, only one
single placenta will develop. This single monochorionic (MC) placenta serves both

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Table 1
Timing of twinning
Days post
conception

Amnionicity

Chorionicity

Frequency

04
48

Diamniotic
Diamniotic

Dichorionic
Monochorionic

8 12

Monoamniotic

Monochorionic
twins

One-third of monozygous twins

Approximately two-thirds
monozygous twins
Five percent of monozygous
twins
Conjoined twins

12 + a
a

Timing for conjoint twins is theoretical and only suggested by animal models.

embryos, and in the majority of cases, contains anastomoses of blood vessels that connect
the embryos.
After about the eighth day, the MC MZ pair will share a common amniotic sac, in
addition to the common MC placenta [4]. About 5% of MZ twins are monochorionic (MC)
and monoamniotic (MA). Twinning after the second week results in the very rare
phenomenon of conjoined twins (see Table 1).
All MC twins are MZ by definition, and this is still the gold standard when defining
monozygosity. Although often seen in animals, vascular communications in dichorionic
placentae in man are extremely rare [5]. The combination of monochorionicity and arterioarterial anastomoses is a better proof of monozygosity than any genetic test currently
available. If placentation has not already been established by ultrasound in the first
trimester, it relies on placental examination by pathologists; unfortunately, this still has not
become routine clinical practice in most hospitals, despite numerous pleas in the literature
[6,7].

3. Ante-natal environmental factors

3.1. Chorionicity, twin twin transfusion syndrome and discordant birth weight
Anastomotic connections between foetal circulations are present in around 90% of MC
placentas. These anastomoses can result in the twin to twin transfusion syndrome (TTTS)
[8]. This can result either in a chronic ante-partum transfusion or acute intrapartum
transfusion. In the former event, growth discordance occurs and there are risks for both the
donor and recipient. These include the possibility of the donor becoming malnourished
and growth retarded, while the recipient is at risk of cardiac hypertrophy, polycythaemia
and hydramnios. In general, the mortality and morbidity rate for both twins in this situation
is high without intervention [9]. The acute transfusion syndrome occurs intrapartum and
causes increased mortality and morbidity, through both hypovolaemia and hypotension in
one twin, and polycythaemia in the other.
Even without TTTS, discordant birth weight in MZ twins remains common as a result
of: (1) unequal in-utero blood supply, and hence growth; and perhaps (2) in theory,
unequal division of inner cell mass at twinning. Although such differences may diminish

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with age, there is a growing body of evidence that significant discrepancy in birth weight
may lead to long-lasting physiological changes in both twins. The concept of foetal
programming proposes that intrauterine growth affects long-term growth and metabolism
in later life. Epidemiological studies linking low birth weight with hypertension and
coronary artery disease in adult life suggest that undernutrition before birth programmes
later cardiovascular outcome [10]. Associations between small for dates babies with later
insulin resistance and cardiovascular disease are consistent with the hypothesis that late
gestation may be a window of sensitivity to nutrition in terms of its influence on later
cardiovascular disease. In twins discordant for the development of non-insulin dependant
diabetes (NIDDM), birth weight has been found to be lower in the affected twin [11].
Investigators continue to use twins with discordant birth weight as a means to test the
foetal programming hypothesis, while assuming the twin pair would share common
confounding variables such as social class, genetic endowment and post-natal environments. Two teams have recently reported the importance of birth weight in twins,
independent of genetic differences, in influencing their blood pressure as adults [12].
Evidence for foetal programming has even been found in early infancy: in a small cohort
of MZ twins, where a twin twin transfusion had occurred, differences in arterial
distensibility were found in the donor twin when compared to the recipient [13].
Appealing though the findings from twin studies may be, the extent to which they are
generalisable to singleton population is unknown. It is not fully understood if either the
mechanism for growth discordancy or the responses to undernutrition differ between twins
and singletons.
3.2. Chorionicity, cognition and personality
Many twin studies have demonstrated the high heritability of cognitive abilities. It has
been reported that MZ twins IQ test scores are almost as highly correlated as those
obtained from testing and re-testing the same person. This finding is striking, given the
very high test and re-test reliability of IQ tests [14].
Whether placentation in MZ twins affects cognitive function remains a controversial
subject. MC MZ twins (where twinning occurs later when compared to DC MZ twins)
have been suggested to be more similar cognitively and behaviourally than DC MC twins.
Although there is some agreement that MC MZ twins are more alike in personality, the
findings are not consistent for concordance in intellectual abilities [15]. Chorionicity
(perhaps a surrogate marker for the timing of twinning) may be an important factor that
underlies cognitive and personality differences between MZ twins, but plausible biological
mechanisms are still yet to be elucidated. A prospective cohort study on a large MZ twin
sample, where chorionicity are accurately and reliably determined, would be required to
fully answer some of these questions.
3.3. Differential infections and teratogens
Ascending infections (chorioamnionitis) are more likely to affect the lower gestation
sac [3]. Differential congenital infections are thus probably more common than
congenital infections, where both twins are equally infected. Infective agents include

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109

the usual list of toxoplasma, rubella, herpes and cytomegalovirus; all can adversely affect
MZ twins to varying degrees. Where congenital HIV infections are concerned, birth
order emerges as a major risk factor. Firstborn twins tend to contract HIV infection from
their affected mothers more often than second born twins [16]. In cases where the
infection is perinatally acquired during delivery, it has been suggested that the twin
closer to the cervix may experience greater exposure to infected blood than twins located
higher in the uterus. Maybe due to a higher rate of obstetric complications in births of
twins or reasons not fully understood, the rates of HIV infection in twins are higher than
that of singletons [17].

4. Genetic mechanisms
It is a widely held belief that MZ twins are genetically identical; and that subsequent
phenotypical discordances are attributable to environmental influences alone (shared or
nonshared), altering and modifying the expression of the otherwise identical genetic
endowment. Twin studies have long been used to estimate the genetic component in a
range of conditions, from medical and psychiatric disorders to variations in somatic and
psychological phenotypes. The central assumption of these studies is that MZ twins,
formed from the division of a single fertilised egg, are genetically identical, whereas
dizygous (DZ) twins, which result from two fertilised ova are genetically no more similar
than siblings born from separate pregnancies. The degree of similarity between MZ pairs
(concordance) over that of DZ pairs is taken as evidence of genetic contribution in the
aetiology with respect to the phenotype studied. The validity of this assumption and the
ability of twin studies to fully allow both ante-natal environmental effects and mutational
genetic effects are still being debated [18].
There is now an ever-growing body of evidence that MZ twins are not always
genetically identical. A number of phenotypic discordances in MZ twins have been
demonstrated to be caused by genetic differences alonethat is, without having to invoke
ante-natal environmental factors to account for their phenotypic differences. Furthermore,
divergent epi-genetic modifications within a MZ twin pair, can lead to differential
expression of inherited diseased genes.
Genetically, MZ twins can be different at the level of (1) chromosomes or (2) DNA:
1. at the level of karyotype (cytogenetics)i.e. the number or morphology of
chromosomes may vary; and
2. at the level of molecular geneticsthere may be
(i) DNA mutations or
(ii) epi-genetic modifications, such as differences in promoter region
methylation, that suppress the expression of the DNA coding regions, and
skewed X-chromosome inactivation by methylation shut-down of the whole
X chromosome.
It is worth bearing in mind that the examples cited in this review are based on the
findings detected by laboratory techniques currently available. This means the detected

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differences are limited by the resolution power of current technologies. As more advanced
technologies are becoming available for more detailed genomic comparison and are
applied to study MZ differences, it is possible that more MZ phenotypical discordance
may be found to have a genetical or epi-genetical basis.
4.1. Heterokaryotypical divergence and chromosomal mosaicism
MZ twins can have different chromosomal composition (heterokaryotypia). A well
documented example for this is MZ discordance for gender and Ullrich Turner
syndrome (UTS)that is, one twin is phenotypically male and the co-twin, a
phenotypically female Turner [20]. This is thought to be the consequence of an early
postzygotic mitotic error, resulting in heterokaryotic twinning that involves nondisjunction or anaphase lag of the Y chromosome. As a result, one twin is 47,XYY or 46,XY
[20] or mosaic 45,X/46,XY [22] (resulting in a phenotypical male); and the co-twin is
45,X or mosaic 46,XY/45,X (resulting in a phenotypical Ullrich Turner female). The
timing of this mitotic nondisjunction determines the presence and degree of mosaicism
in one or both twins. There have been more than nine reported cases of such discordant
MZ twin.
MZ discordance for Downs syndrome (trisomy 21) or Klinefelter syndrome
(47,XXY) are uncommon, though Rogers et al. [23] reported a single case of MC
MZ male twins who were discordant for trisomy 21. Interestingly, each was non-mosaic
in fibroblast lines, but have mixture of cells in blood derived from 46,XY/47,XY,1 [21]
cell lines. The theoretical explanation is that Downs and Klinefelter syndrome commonly result from a pre-zygotic nondisjunction, whereas UTS from post-zygotic nondisjunction pairs [21].
4.2. Mosaicism, chimerism and pseudo-mosaicism
For singletons, chimera is an organism with tissues of two or more different genotypes,
often as a result of grafting or introduction of very early embryo stem cells from another
genetically different individual(s). A chimera is often constructed experimentally in
animal studies. In contrast to this, mosaicism denotes an organism comprising clones
of cells with different genotypes (often caused by mutations or mitotic errors) deriving
from the same zygote.
For MZ twins, such a distinction is more problematicas by definition, both embryos
are derived from the same zygote. So strictly speaking, any genetic heterogeneity in MZ
twins should be classified as mosaicism. However, some authors used the term
chimerism to describe transplantation of stem cells from one twin to its MZ co-twin,
if genetic divergence has already occurred prior to twinning, i.e. twin A is subtly different
from twin B genetically; and twin B has some stem cells from twin A in certain tissues.
Mosaicism is reserved to describe divergent cell lines as a result of mutations occurring
within one twin after twinning. However, such distinction is not strictly applied within the
twins literature. Often, it is difficult to make such distinction retrospectively.
In monochorionic twins who share the same placenta, cross-placental transfusion
enable blood and stem cells to be transferred from one twin to the otherdue to

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111

placental vascular anastomoses. This results in pseudomosaicism or chimerism (i.e.

transfer of the co-twins stem cell into the bone marrow during foetal development). For
genomic comparison studies of monochorionic MZ twins, it is therefore important to
conduct tissue (i.e. skin fibroblasts) genotyping, rather than relying on blood lymphocytes alone [24].
An example is the case report the pair of MC twins discordant for trisomy 21 by Rogers
et al., as cited above. They found only one karyotypes in fibroblast cell lines from each
twin (one with normal karyotype; another with Downs karotype), but in blood, both
karyotypes are found in both twins, indicating the presence of chimerism in blood (and in
bone marrow), but not in somatic cell lines.
Mosaicism can arise from mitotic error in early developmentresulting in a mixture
of cells with divergent karyotypes (e.g. a mixture of 45,X and 46,XY cell lines in the
UTS co-twin of gender discordant MZ twin). In some cases, the presence of mosaicism
may vary in different tissues from one single individual. In such cases, multiple tissue
cultures are required to establish mosaicism. Edwards et al. [25] reported a pair of MZ
heterokaryotic twins with a UTS female and a normal male phenotype. The male,
despite normal sexual development to age 21, had two skin fibroblast cultures and two
lymphocyte culture showing a nonmosaic 45,X karyotype [25]. The authors concluded
that their patient would probably show mosaicism, and if gonadal tissue was sampled,
the presence of Y chromosomal material would be found. Reindollar et al. [22] reported
another pair of MZ twins with a UTS female and a normal male. They examined two
separate cultures of penile skin of the male co-twin, showing one single 45,X cell; with
49 cells of 46,XY; while the cultures of gonadal tissue showing 100% 46,XY. This
suggests that low level mosaicism may exist in the phenotypically normal co-twin in
these cases.
4.3. Epi-genetic modification, methylation and skewed X-inactivation
Methylation is an epi-genetic mechanism by which the expression of an sequence of
DNA can be modified by becoming silenced or switched off. This is achieved by
attaching a methyl group to the cytosine nucleotide in CpG islands [26]. CpG islands
are clusters of cytosine and guanine repeats, commonly found near a gene coding
DNA region. Methylation of CpG islands adjacent to a gene often leads to its
inactivation [27].
In addition to the silencing of a specific gene, methylation is also involved in the
whole-scale inactivation of the surplus X chromosome in human femalesa process
called X-inactivation or lyonization. In the majority of cases, X-inactivation is a
random process. That is, both X chromosomes in a female have an equal chance of
being switched off by methylating the whole X chromosome. However, for reasons
not yet fully understood, X-inactivation can be skewed or non-random in a minority
of individuals, that is, the X chromosome of one parental origin is preferentially
inactivated [28].
Some authors report that skewed X-activation is more common in female MZ twins
than predicated by chance, though this view is still subjected to debate. They propose that
skewed X-inactivation may give rise to clonal differences within the post-zygotic inner

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cell mass and may trigger the very process of twinning [29,30], thus accounting for an
excess of females among MZ twins, especially among monochorionic MZ twins. This
view remains controversial. Derom et al. [31] did not find an excess of female twins in an
epidemiological study of multiple births.
Along with the development of more robust technology in detecting skewed Xinactivation, a number of cases with non-random X-inactivation and MZ phenotypic
discordance have been identified. They consist of expressed X-linked diseases in
females. Examples reported include fragile-X syndrome [32], colour blindness [24],
Duchenne muscular dystrophy [33], haemophilia B, G6PD deficiency, Aicardis syndrome, Hunter and Fabrys disease in discordant female MZ twins [34]. The clinically
affected twin has non-random inactivation predominantly of the X-chromosome carrying
the wild gene, while the unaffected twin either has predominant inactivation of the Xchromosome carrying the mutant gene or has random X-inactivation.
4.4. Post-zygotic genetic mutation
Theoretically, post-zygotic DNA mutation in discordant MZ twins can occur at the
level of
(1)
(2)
(3)
(4)

Dominant genes;
Recessive genes;
Imprintable genes; or
Genes involved in quantitative trait loci.

Confirmed and proven molecular genetic evidence are still lacking, maybe in part due
to the limitation of currently available genomic comparison techniques. A number of
technical innovations are currently under development, but not yet sufficiently mature for
routine application.
The authors are unaware of any report demonstrating proven DNA mutations that
account for discordant phenotypes in MZ twins. However, there exist reports on MZ
discordance for conditions transmitted by well documented autosomal dominant inheritance. Some include conditions in which imprinting is implicated.
For autosomal dominant conditions, Vaughn et al. [35] reported a pair of MZ twins with
neurofibromatosis, showing markedly different density of cafe-au-lait spots, assuming the
aetiology to be a de novo mutation. Easton et al. [36], however, found striking
concordance of 0.97 correlation in the exact counts of neurofibromas for five of the six
MZ twin pairs.
A number of MZ twins discordant for the severity of tuberous sclerosis have been
reported. Among those documenting the phenotypical differences, Brilliant et al. [37]
demonstrated a single discordant hybridizing fragment using high-resolution Southern
blotting technique. However, the discordant fragment has not been pinpointed on the
specific gene sequence responsible for tuberous sclerosis. The molecular evidence therefore remains inconclusive.
A number of reports on MZ twins concordant for Williams syndrome, also an
autosomal dominant condition, found differences in timing and severity in the develop-

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113

ment of abnormalities, especially inguinal herniae and facial anomalies and other signs
attributable to connective tissue abnormalities [38].
Wiedemann Beckwith syndrome (WBS) is a congenital anomaly syndrome, consisting of exomphalos, macroglossia and gigantism, with an increased risk of developing
rare embryonal cell tumours. Though autosomal dominant inheritance (preferentially
through the mother) is well recognised [39], sporadic cases with paternal uniparental
disomy of 11p15 loci may implicate that imprinting is involved in WBS. A number of
discordant MZ twins for WBS have been reported, but the precise molecular mechanisms for their discordance have not been clearly established [40].
There are two recent reports examining MZ twins discordant for schizophrenia. Tsujta
et al. [41] analysed genomic DNA of a pair of MZ twins discordant for schizophrenia by
using two-dimensional electrophoresis display, following PCR and restriction enzyme
digest. They used both methylation sensitive and non-sensitive enzymes. They found
discrepancies of at least two spots out of approximately 2000 spots on the autoradiograms
of the pair. Both of the spots were estimated to represent 300 400 base pairs. The study
can be criticised for lacking specificity, validity as well as statistical power; and
contamination by errors or artefacts cannot be ruled out. On the other hand, it can be
regarded as providing preliminary evidence that MZ twins may differ at the levels of DNA
or methylation.
Smith et al. [19] used targeted genomic differential display method to evaluate,
quantitatively, the level of genome similarity in a group of twin presented to them as
MZ twins concordant and discordant for schizophrenia. At the DNA level, they found
three distinct patterns. One type had DNA similarity levels equivalent to that of unselected
sibling pairs, suggesting these to be dizygous twins misidentified as monozygous twins. At
the other extreme was a group with a very high level of similarity, suggesting these are true
monozygous twins. The surprising finding was an intermediate group, lying between true
monozygous and dizygous twins. They found all concordant twin pairs were true
monozygotic. The mixed discordant and concordant twin pairs belonged to the intermediate group. They concluded that their findings brought into question a large number of
experiments that depended on accurate twin zygosity determinations for measuring the
heritability and penetrance of the condition.

5. Differences of unknown origin

5.1. Mirror twinning
Mirroring in MZ twins is a fascinating, but poorly understood and poorly defined
cause of phenotypic and perhaps behavioural discordance. It has been estimated to occur
in 25% of MZ twins [42]. The spectrum extends from those twins with just oppositesided occipital hair whorls, to those where one twin has complete reversal of body organs
(situs inversus). The term is perhaps most commonly used for those MZ twins with
discordant handedness (right and left handedness). In itself, this suggests some degree of
asymmetry of cerebral hemisphere dominance. Researchers have recently confirmed
using functional magnetic resonance brain imaging on MZ twins with discordant

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handedness that hemispheric lateralisation is indeed also present [43]. The same team
suggests that this finding may complicate interpretation of twin research in illnesses
where cerebral lateralisation is important to their pathology (such as schizophrenia,
dyslexia, autism, depression) [44].
5.2. Hair, eyes and fingerprints
Zygosity examinations and questionnaires rely on finding differences between twins.
Although very minor degrees of phenotypic discordance have been recognised in MZ
twins, it is apparent the spectrum is widening. Different hair and eye colour would
automatically qualify for a DZ label in all established questionnaires, but both have
recently been described in male MZ twins [45,46]. Putative mechanisms for such
discordances range from unequal division of the inner cell mass, to post-zygotic mutations.
It is likely that complex gene environment interactions play a part in such cases.
Similar mechanisms where the ante-natal environment impacts on a genetically
predetermined trait may account for the fingerprint differences seen in MZ twins. Police
departments have long been grateful for this phenomenon, which ensures that MZ twins
cannot commit the perfect crime so often presented in works of fiction. Forensic studies
in fact show that although MZ twins have different fingerprints the pattern, ridge count and
other minutiae are nevertheless much more similar than those seen in DZ twins [47].
Variation in vascular supply to each twin can occur during the second prenatal trimester
the critical period when fingertip dermal cells migrate to form ridges. This is also the
period when neural cells migrate to the cortex and several investigators have tried to
exploit this temporal relationship in an attempt to use fingerprints as marker for prenatal
anatomical insults that may have affected the twins differently.
5.3. Major malformation discordances
Foetal pathologists have long recognised discordances for major malformations in MZ
twins [48]. Many of these malformations do not have simple genetic origins, but are likely
to be multifactorial. Examples commonly described include neural tube defects, cleft lip
and palate, and symmelia [4]. While it is not clear how these discordant events arise, in
many cases, the apparently unaffected co-twin also has a less severe manifestation of the
same disorder. The implication in these cases is that the predisposition for the malformation is expressed in both twins.

6. Summary
This review highlights some of the important findings since Francis Galton, the father
of twin research, first thought of using twins to estimate the impact of genes in 1876 [49].
His paper on the use of twins as a criterion of the relative powers of nature and nurture
launched the whole field, which has since seen major advances in twin foetal development
and twin genetics. This review has demonstrated the problems in assuming that being
monozygous is synonymous with being identical.

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115

Apart for academic interest and implications for twin research, these facts also have
clear implications for clinical practice. In the case of a twin pair found to be discordant for
a major malformation, the assumption should not be that they are automatically DZ. They
may be MZ and, more importantly, MC. In a case of heterochromia iridum (different
colour irises) in MZ twins described by St. Clair et al. [45], immunosuppressive therapy
following a renal transplant was needlessly continued for 15 years because dizygosity had
been assumed. In their case discussion, the authors of this paper emphasised that the
heterochromia discordance must fall within the acceptable spectrum of MZ status. This
review demonstrates that as our understanding of MZ twinning increases, the spectrum
will continues to widen, and the term identical twins should be replaced by the more
accurate term monozygous twins.
The importance of establishing the zygosity of twins has been stressed in the literature.
Keith and Machin [50] have summarised many of the issues: For reasons of personal
rights to identity, medico-legal responsibility, potential for transplantation, early education,
and concordance/discordance for genetic disease, many feel that routine determination of
twin zygosity at birth is needed and should be implemented in the near future. Apart from
the benefits to the twins and their parents, the consequences for research in twins and
genetics would be enormous, since there remain many puzzling aspects of twinning. To
this list is now also added the importance of establishing chorionicity, preferably by
ultrasound in very early pregnancy.

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