Zygosity testing should be encouraged for all same-sex twins

Abstract

Twin pairs are either monozygotic (MZ) or dizygotic (DZ). Diagnosis of zygosity has traditionally been based on sex, genetics and/or chorionicity (Derom et al. Twin Res, 2001;4:134–6). A monochorionic placenta, determined using first-trimester ultrasound scans and confirmed by placental examination at birth, means the twin pair is MZ, with rare exceptions. Different-sex, dichorionic pairs are usually DZ. However, as approximately one-third of MZ pairs and nearly all DZ pairs have separate chorions and placentae, it is impossible to determine zygosity by placentation alone. For these pairs, a genetic test is essential.

The above rules of zygosity determination are frequently misunderstood, mainly because of the false assumptions that all dichorionic twin pairs are DZ and that MZ pairs must be physically identical. Up to one-third of families could be misinformed about twin zygosity, resulting in difficulties with medical decision-making, confusion and/or distress (Cutler et al. Twin Res Hum Genet 2015;18:298–305; van Jaarsveld et al. BJOG 2012;119:517–18).

There are many documented reasons why zygosity knowledge is medically important (Derom et al. Twin Res 2001;4:134–6; Keith et al. J Reprod Med 1997;42:699–707). Identification of monochorionicity allows referral for clinical monitoring to detect twin-to-twin transfusion, which, if not managed correctly, poses a high risk of fetal death and neurological injury. Postnatally, MZ pairs are perfectly compatible donors for one another. The diagnosis of a disease in one twin typically means that the co-twin is at increased risk, more so for MZ pairs. Furthermore, due to placental blood sharing between MZ pairs, genetic tests should be performed on tissues other than blood.

Twins and parents attest that zygosity knowledge is important for understanding the phenotypic differences between twins, defining their social relationships, defining themselves as individuals, determining the likelihood of further twins in the family and for avoiding embarrassment when questioned (Derom et al. Twin Res 2001;4:134–6; Cutler et al. Twin Res Hum Genet 2015;18:298–305; van Jaarsveld et al. BJOG 2012;119:517–18). Zygosity knowledge can also invoke a positive emotional response (Cutler et al. Twin Res Hum Genet 2015;18:298–305). Zygosity is valuable for twin research, in which free zygosity testing is often offered (Derom et al. Twin Res 2001;4:134–6). For all the above reasons, knowledge of chorionicity and zygosity has been called a ‘birthright’ (Keith et al. J Reprod Med 1997;42:699–707).

We would like to encourage the standard practice that same-sex twins and their families be advised that if they wish to know the pair’s zygosity, the only way to be certain is to have a zygosity test. In many countries the current cost is €100 to €300 (US$100 to US$300). We understand that some may not wish to know and that, in some families, there may be ethical implications if only one of a pair of twins seeks such information, but counselling options are available in such instances. We also support raising awareness of the methods for determining chorionicity and zygosity. We believe that this will benefit both twins and researchers.