Prenatal diagnosis of female monozygotic twins discordant for Turner syndrome: implications for prenatal genetic counselling

Abstract

We describe a set of monozygotic (MZ) female twins, one of whom presented with a typical Turner syndrome (TS) phenotype and the other a normal female phenotype. Prenatal fetal ultrasonographic examination showed a monochorial diamniotic pregnancy with a hygroma colli and growth delay in Twin A and no anomalies in Twin B. Karyotypic analysis performed on fetal blood samples demonstrated a 46,XX/45,X (23/2) mosaicism in Twin A and a normal 46,XX chromosome constitution in Twin B. At birth, Twin A presented with a typical TS and Twin B had a normal female phenotype. Postnatal cytogenetic investigation of blood lymphocytes showed the same 46,XX/45,X mosaicism in both twins: 46,XX/45,X (40/7) in Twin A and 46,XX/45,X (40/5) in Twin B. Further investigations at the age of 10 months showed in Twin A a 46,XX/45,X (98/2) mosaicism in lymphocytes and 100% of 45,X (50 analysed cells) in fibroblasts, and in Twin B a normal 46,XX (100 analysed cells) chromosome constitution in lymphocytes but a mild 46,XX/45,X (78/2) mosaicism in fibroblasts. Monozygosity was confirmed by molecular analysis. To our knowledge, this is the first report of prenatal diagnosis of MZ female twins discordant for TS. Review of reported sets of MZ female twins (eight cases) or triplets (one case) discordant for TS shows, as in the present case, that the phenotype correlates better with the chromosomal distribution of mosaicism in fibroblasts than in lymphocytes. In the blood of MZ twins chimerism may modify the initial allocation of the mosaicism. These results suggest that, in cases of prenatal diagnosis of MZ female twins discordant for TS, the phenotype of each twin would be better predicted from karyotype analysis of cells from amniotic fluid than from fetal blood.

Discordance in Nuchal Translucency Measurements in Monochorionic Diamniotic Twins as Predictor of Twin-to-Twin Transfusion Syndrome

“…Several cases have been described of monochorionic twin pairs concordant for a chromosomal abnormality but with dissimilar NT values (Pandya et al, 1995;Sebire et al, 2000;Vandecruys et al, 2005). In addition, although monozygotic twins are considered genetically 'identical', a small number of discordances for chromosomal abnormalities have been described (Gilbert et al, 2002;Nieuwint et al, 1999). To account for heterokaryotypic twinning, individual fetal karyotyping should be considered in monochorionic twins.…”

Genetic or epigenetic difference causing discordance between monozygotic twins as a clue to molecular basis of mental disorders

“…After that, a number of cases of MZ twins having discordant phenotypes arisen from de novo mosaic chromosomal abnormalities were reported. These include Turner syndrome, 22 skin pigmentation, 23 minor anomalies, 24 and sex phenotypes. 25,26 Since there are a number of case reports of MZ discordant twins caused by mosaicism of chromosomal abnormality, it may be a frequent cause of discordance in MZ twins.…”

Epidemiological, endocrine and metabolic features in Turner syndrome

“…There is a well-described increased intrauterine mortality, especially during the first trimester (peaking in gestational week 13) (12), but after this period there is no or only slightly increased intrauterine mortality (11). Prenatal diagnosis of TS is not always correct, especially when taking into account mosaic cases (11, 13 -16), and it is even more complicated in rare cases with twins (17). This means that one should not rely solely on a karyotype before deciding what action to take (legal abortion or continued pregnancy), but rather one should perform a high-resolution ultrasound scan or fetal echocardiography and other modern modalities, in order possibly to diagnose additional features of Turner syndrome (i.e.…”