Monozygotic twins discordant for single umbilical artery andcongenital heart disease

Daisuke Nakayama, MD, Hideaki Masuzaki, MD, Shuichiro Yoshimura, MD, Shingo Moriyama,MD, and Tadayuki Ishimaru, MD

Nagasaki, Japan

We report a case of monozygotic twins. One twin had a single umbilical artery and the other co-twin hadcongenital heart disease. This case and a review of the literature suggest that local environmental factors areimportant in the pathogenesis of these malformations although genetic factors cannot be excluded.(Am J Obstet Gynecol 1998;179:256-7.)

Key words: Monozygotic twins, single umbilical artery, congenital heart disease

Although the presence of a single umbilical artery1

and congenital heart disease are common congenitalanomalies, causal factors have been rarely identified.Twin studies to distinguish between environmental andgenetic mechanisms of these malformations have notshown consistent results. We report a case of monozy-

From the Department of Obstetrics and Gynecology, NagasakiUniversity, School of Medicine.Received for publication July 11, 1997; accepted October 22, 1997.Reprint requests: Daisuke Nakayama, MD, Department of Obstetricsand Gynecology, Nagasaki University School of Medicine, 1-7-1Sakamoto, Nagasaki 852, Japan.Copyright © 1998 by Mosby, Inc.0002-9378/98 $5.00 + 0 6/1/87085

Nakayama et al July 1998Am J Obstet Gynecol

Volume 179, Number 1 Nakayama et al 257Am J Obstet Gynecol

gotic twins in which one twin was affected by single um-bilical artery and the co-twin was affected by congenitalheart disease, indicating that local environmental factorsare important in such abnormalities. The factors likely tobe involved and the possible contribution of genetic fac-tors are discussed.

Case reportA 25-year-old woman, gravida 2, para 0, was seen at 6

weeks’ gestation for her first prenatal visit. She hadHashimoto’s disease that was managed with levothyrox-ine at that stage and became euthyroid during the rest ofpregnancy. Transvaginal ultrasonography at 10 weeks’gestation showed a gestational sac containing 2 fetuses(2.5 cm and 2.5 cm in crown-rump length) separated byvery thin membranes. She was admitted to our hospital at26 weeks’ gestation after the detection of a small amountof pericardial effusion in the first twin on routine ultra-sonography. At that stage the estimated fetal body weightof the first and second twins was 678 and 875 g, respec-tively. Although the volume of the amniotic fluid was nor-mal, the presence of twin-to-twin transfusion from thefirst to the second twin was suspected. Color Doppler ul-trasonography showed that only the first twin had a sin-gle umbilical artery, lacking the left umbilical artery.

Since admission to our hospital, both twins showed nosigns of worsening of twin-to-twin transfusion, until 31weeks’ gestation when the waveforms of the umbilicalvein of the second twin showed fluctuation. We also no-ticed increased diameter of the umbilical vein, increasedcardiothoracic ratio, and tricuspid regurgitation in thesecond twin. These findings prompted us to perform acesarean section at 31 weeks’ gestation.

The discordance between the twins in body weight atbirth was 20%, the first twin weighed 1214 g, and the sec-ond weighed 1516 g. Both cords originated very close toeach other from the center of the placental disk.Perfusion study conducted at that stage showed vein-to-vein anastomoses on the chorionic surface. On the otherhand, histologic examination showed monochorionic-di-amniotic twin placenta, and only the first twin had singleumbilical artery. The second twin had complex heartanomalies, including patent ductus arteriosus, ventricu-lar septal defect, and atrial septal defect. In contrast, thefirst twin had no congenital anomalies other than singleumbilical artery. Both twins were female and had type O,Rh-positive blood. We verified the zygosity by deoxyri-bonucleic acid analysis by use of highly polymorphic mi-crosatellites. We used a laser-based automated deoxyri-bonucleic acid sequencer to determine the size ofpolymerase chain reaction product from tetranucleotiderepeats amplified with fluorescently labeled primers.Cord blood deoxyribonucleic acid of the twins showedidentical patterns for four loci containing CSF1PO,

TPOX, TH01, and vWA, indicating >99.98% probabilityof the twins being monozygotic (GenePrint FluorescentSTR1 Systems, Promega Corporation, Madison, Wis).

Comment

Because monozygotic twins arise from a single fertilizedovum that subsequently divides into two similar structures,monozygotic twins are presumed to be genetically identi-cal, and they usually have similar characteristics. However,monozygotic twins are not always concordant for congeni-tal malformations. As for congenital heart disease and sin-gle umbilical artery, both concordant and discordant casesof monozygotic twins have been described, suggesting thatnot all cases share the same cause. Accurate concordancerates are unknown at present.

To our knowledge, this is the first report on monozy-gotic twins, with only 1 twin being affected with singleumbilical artery and only the other twin with congenitalheart disease. This suggests that local environmental fac-tors are largely responsible for these malformations.Teratogenic factors, such as infection, drugs, and mater-nal disease, were not remarkable in this case. It is possi-ble, however, that factors resulting in monozygotic twinformation might have some effects. For example, postzy-gotic events, such as erroneous mitosis, may lead to 2 ormore cell clones in the inner cell mass or unequal alloca-tion of cell numbers in the monozygotic twins. It is alsopossible that vascular patterns of monochorionic pla-centa may have caused significant environmental differ-ences between monozygotic twins in our case; differ-ences in placental blood supply between the twins andinterfetal anastomoses might lead to discordant embryo-genesis.

Genetic factors should also be considered because re-cent work suggests that monozygotic twins are not alwaysidentical. Indeed, many genetic forms of discordancehave been reported in monozygotic twins and may evenplay a role in the monozygotic twinning process.2

Therefore discordance cannot simply reflect a lack ofcontribution of genetic factors. A complex interactionbetween genetic and environmental systems rather thana single specified cause might be involved.

REFERENCES

1. Persutte WH, Hobbins J. Single umbilical artery: a clinicalenigma in modern prenatal diagnosis. Ultrasound ObstetGynecol 1995;6:216-29.

2. Hall JG. Twinning: mechanisms and genetic implications. CurrOpin Genet Dev 1996;6:343-7.