Address correspondence to Richard Jaffee, MD, Department of Obstetrics and Gynecology, University of Illinois at Chicago, 840 South Wood Street, Chicago, IL 60612-4324, Ph: 312-996-7300, Fax: 312-996-4238, ¶Dept. of Pathology, Humana Hospital, and Department of Pathology, University of Illinois at Chicago.

Introduction

Monozygotic twinning is a rare event that occurs due to fission of the fertilized ovum at the earliest stages of embryogenesis¹. Mono­zygotic twinning includes a spectrum of syndromes whose features depend on the time of fission. Depending on the timing twinning will result in two separate embryos, and the fetal sacs may be either dichorionic-diamniotic, monochorionic-diamniotic or monochorionic-monoamniotic, with the latter occurring with later fission^1,2. Late or incomplete splitting leads to conjoined twinning, which occurs when the embryonic disk has already formed^1,2.

It is well established that congenital anomalies are found more frequently in monozygotic twinning than in singleton pregnancies^3,4.

The anomalies are of different types: some are related to the twinning process itself, others are due to vascular factors, and a few are structural malformations not exclusively found in twins but observed more frequently in monozygotic twins^1,4,5. The frequency of congenital malformations increases when the twinning is late; therefore, we expect to see malformations more frequently in conjoined twins⁴.

This is a description of conjoined twins demonstrating the most severe anomalies in live born infants.

Case report

A 15-year-old black, G₁P₀ was referred for a routine obstetrical examination at 27 weeks gestation. Sonographic examination revealed a twin gestation. Both infants had severe malformations and they seemed to be connected along the chest and abdomen (fig. 1).

Fig. 1: Continuity of the chests.

There were two separate hearts that were in close proximity (fig. 2).

Fig. 2: The two hearts are in close proximity.

Separate abdominal structures could not be seen. The fetuses differed in size; one was appropriate for gestational age (by BPD), but the second fetus was much smaller (fig. 3).

Fig. 3: The right-sided twin is much smaller than the left.

The lower limbs were not clearly visualized, and there was a large cystic mass arising from both lower spines (fig. 4).

Fig. 4: An ill-defined mass arising from the caudal end.

All limbs were abnormally positioned and did not appear to move.

The diagnosis of conjoined twins was suspected. The mother opted to continue the pregnancy, and at 32 weeks a cesarean section was performed due to premature labor and spontaneous rupture of the membranes. The infants were born with Apgar scores of two at one minute and two at five minutes, and died one hour after birth.

Autopsy

The bodies of male twins, facing each other and weighing a total of 3120g, were joined at the thorax and upper abdomen (fig. 5).

There was a large lower abdominal wall defect involving both infants associated with evisceration of the abdominal contents. The infants and the duplicated organs were of unequal size. Opening of the thorax revealed two tracheae, thymuses, superior venae cavae, esophagi and aortae. A single pericardial sac enclosed two hearts with abnormal situs.  

There was only one inferior vena cava with a common transverse venous channel, communicating with the left atrium of one infant and the right atrium of the other (fig. 6).

Fig. 6: Dissection of the two heart-lung preparations. Note the common transverse vein.

The heart of the smaller twin was considerably more abnormal and consisted essentially of a tetralogy of Fallot type of malformation.

Two sets of lungs were found, both showing severe pulmonary hypoplasia (fig. 7). A single horseshoe-shaped liver was found, fused in the epigastrium. There was duplication of the upper gastrointestinal tract and duodenum, a single jejunum, ileum and appendix, and a short colon that communicated with an identifiable urogenital sinus of one infant, and a perineal fistulous tract of the other infant. The anus was atretic in both infants. Four testes were found, all intra-abdominal. Each infant had a single cystic-dysplastic kidney with hydroureter and distal ureteral atresia. No bladder was identified.

The smaller twin had a spina bifida with a meningomyelocele and a small myelocystocele involving the lumbosacral spine, while the larger infant had a large myelocystocele with a vertebral defect involving the lower thoraco-lumbar and sacral regions (fig. 5). Both infants had severe kyphoscoliosis, absence of pubic rami, and contracture of the limbs, especially knees, elbows and ankles. There were abnormalities of the external genitalia, with rudimentary cleft scrotum and rudimentary penile-like tissue present in both infants. There was a single immature placenta, with amniotic fusion to the body wall defect. Two very short umbilical cords ran through the amniotic membranes (fig.5), each containing only two vessels. The brain of the smaller baby was considerably smaller than that of the co-twin.

Discussion

Pathogenesis

Conjoined twins are thought to occur when the process of monozygotic twinning takes place at the later stages of early embryogenesis or is incomplete². The incidence of congenital malformations is significantly increased in monozygotic twinning as compared to dizygotic twinning^3,4. For this reason, it has been postulated that the same etiological factor could be responsible for both monozygotic twinning and congenital malformations².

Conjoined twins, in most cases, have more malformations than separate monozygotic twins, and this is probably due to a later fission. The malformations occurring in conjoined twins are often more severe and rather major, such as the body wall defect which was present in these twins. Some of these malformations are related to the junction regions, but others are distant from junctional sites and not related to the twinning process itself⁶.

Spectrum of severity

Conjoined twins vary widely. In some cases, two well-developed fetuses exist attached only by a minor superficial connection. In others, only a small part of the body is duplicated or amorphous masses of tissue are found attached to an otherwise normal fetus. The origin of conjoined twins is postulated to be similar to that of normal separate monozygotic twins.

Timing and forms of twinning

If twinning is determined at or before the morula stage, two complete embryos with two amniotic and two chorionic sacs will develop. When twinning occurs at the early inner cell mass stage, (blastocyst) before differentiation of the embryonic disc, two completely separate embryos would be expected, each surrounded by an amniotic sac and associated with a single chorion.

Fig. 8: Schematic drawing demonstrating the outcome of twinning at different stages of early embryonic life.

Top: Fission before the formation of the inner cell mass and any differentiation will produce two embryos with two separate chorions, amnions and placentas.

Middle: Twinning at the early blastocyst stage, after formation of the inner cell mass, will cause the development of two embryos, with one placenta and one chorion but two separate amnions.

Bottom: If separation occurs after the formation of the embryonic disc, the amnion has already formed, and will lead to a monoamniotic, monochorionic pregnancy. Incomplete fission at this stage or later will result in conjoined twins).

If, however, twinning is not initiated until after the embryonic disc is formed, only one amniotic and chorionic sac would develop, containing both twins. If the centers of embryonic growth do not separate adequately, it could be assumed that the transitional regions would be shared by the two embryos and would develop into conjoined twins^1,2.

A different explanation states that splitting of the original embryonic area occasionally takes place and that the extent and site of the splitting determine the different varieties of conjoined twins². The existence of separate or conjoined twins is generally determined prior to the end of the second week following fertilization.

If, after the completion of the twinning process, one twin has an advantage over the other, the one suffering the disadvantage will be reduced in size, as in this case, or may be very abnormal in form. The smaller member of conjoined twins may show a pronounced disturbance in structure and may even be reduced to an undifferentiated mass of tissue resembling a tumor. The same condition holds true in separate monozygotic twins, as one may have an advantage of position and develop normally, while the other becomes malformed. Consequently, mono­zygotic twins need not be as identical as they are commonly expected to be, since there are possible differences in metabolic rates related directly to placental blood supply.

The overwhelming majority (70-95%) of conjoined twins are female.

Types

When the joined twins are each fairly complete, fusion may be anterior (thoracopagus or xiphopagus), posterior (pygopagus), cephalic (craniopagus), caudal (ischiopagus) or abdominal. When doubling is less complete and only parts of the bodies are duplicated, the attachment is often lateral. If the division extends from above downward, there may be two heads and four arms. If the division extends from below upward, it can produce three or four legs. The spine, thorax and pelvis show varying degrees of duplication directly related to the number of extremities. In symmetrical double twins (except the rare xiphopagus that has only the lower portion of the sternum fused), some of the viscera are shared by the two individuals, and surgical separation with survival of both twins depends upon the degree of shared viscera².

The prevalence of congenital heart disease in thoracopagus twins is high and is related to the degree of union. Seventy-five percent of conjoined twins are stillborn or die within 24 hours.  In no study has the maternal use of alcohol, tobacco, drugs or exposure to radiation, or a family history of genetic disease been implicated. The etiology of abdominal wall defects is considered to be due to a failure of proper folding of the early embryo during the process of conversion from the embryonic disk to a cylindrical embryo. Persistence of the extraembryonic coelom results from this faulty folding.

References

1. Romero R, Pilu G, Jeanty P et al: Prenatal Diagnosis of Congenital Anomalies Norwalk, CT, Appleton & Lange, 1988, p 403-408.

2. Potter EL, Craig JM: Pathology of The Fetus and The Infant Chicago,  Year Book Medical Publishers, 1975, p 220-237.

3. Hay S, Wehrung DA: Congenital malformations in twins. Am J Hum Genetics 22:662-678,1970.

4. Schinzel AA, Smith DW, Miller JR: Monozygotic twinning and structural defects. J Pediatrics 95:921-930,1979.

5. Hoyme HE, Higginbottom MC, Jones KL: Vascular etiology of disruptive structural defects in monozygotic twins. Pediatrics 67:281-291,1980.

6. Seller MJ: Brief clinical report - conjoined twins discordant for cleft lip and palate. Am J Med Genet 37:530-531,1990.