Address correspondence to: Robert Roger Lebel, MD, Genetics Services, 360 West Butterfield Road, Suite 245, Elmhurst, IL 60126-5000. Tel: (708)832-4363, Fax: (708)832-9580. (all authors:Central DuPage Hospital, Winfield, IL; Christ Hospital, Palos Heights, IL

Introduction

Some authors¹ attribute to Benedetti² the first description of acephaly/acardia, (acardiac twin) but we believe that earlier woodcuts presented by Schedel³ depict a malformation which might well have been inspired by the observation of a case (fig. 1,2). Warkany⁴ presented reproductions of early cases.

Case report

The pregnancy in a 24 year old G4P3 Mexican-American woman was notable for a complete lack of prenatal care. She presented in labor, at 38 weeks (menstrual age), to a community hospital, where a brief emergency-room ultrasound examination revealed a live fetus and a nondescript shaddow without head or heartbeat. An apparently normal female was delivered vaginally; she weighed 3262g (25-50th percentile), had a length of 46 cm (10-25th percentile) and a head circumference of 34.5 cm (50th percentile); Apgar scores were 8 at one minute and 9 at five minutes. The nondescript mass was an acephalic fetus, which was delivered, also vaginally. The patient reported no unusual events or exposures in this pregnancy, other than some dental work with local anesthetic. The total body weight of the stillborn was 1600g, total length 30 cm. There was no recognizable head, but a mound above sloping shoulders (fig. 3).

In the midst of this mound was a small opening with the appearance of an eye socket (eyelash-like pili) but containing a cartilagenous mass with 5 teeth; the ears were represented by small fleshy peduncles. The left upper extremity was absent and there was also a severe reduction of the right upper extremity. Both lower extremities were intact except for severe bilateral equinovarus malformation at the ankles, and tubular bones shorter than normal for gestational age (fig. 3). In the center of the torso was an oval depression covered by a translucent membrane and containing loops of bowel (midgut) (fig. 4) but no other viscera except for dysplastic kidneys weighing a total of 4g.

Thus, the fetus was notable for: acrania, anencephaly, athymia, apulmia, acardia, anhepatia, asplenia, amelia/micromelia. External genitalia included labia, but there was no vaginal cavity and internal genitalia were completely absent. Radiographs also revealed severe vertebral and rib dysplasia. There was a velamentous cord insertion, and arteriography revealed extensive hypoplasia of the vascular tree with total absence of a pump (fig. 5). Histologic studies of representative samples were notable for dysplasia of the hypoplastic kidneys, and monoamniotic/ monochorionic gestation.

Tissue culture of skin fibroblasts revealed a karyotype of 46,XX (normal for a female). Karyotype was not performed on the normal child, and the family was lost to follow-up immediately upon discharge from the hospital.

Discussion

The incidence of acardia-acephaly is often given as about 1 in 35,000 deliveries, but this is apparently based on a calculation founded on estimates of the incidence of twinning in the population, and the fraction of twin gestations (1%, apparently arbitrary) affected by this abnormality5. It is clear that this conclusion, therefore, is only an approximation.

Most authors have had the opportunity to observe only one or two acardiac/acephalic fetuses6-8. Modern reviewers state that about 400-500 cases have been reported worldwide, but no review known to us surpassed the detail of that by Elben9, who presented 20 cases with superb illustrations (including dissections of some), until the work of Moore et al.11 which includes twice as many cases and a modern perspective.

Pathogenesis

Angiographic/radiographic studies of the placenta and fetus have become an important part of recent reports, but one of the earliest uses of color illustration in the study of birth defects was an engraving of the vascular tree in an acardiac/acephalus fetus, defining the vasculature by injecting the umbilical vessels before dissection7 (fig. 6). Interest has focused on the vessels since the early recognition that these fetuses always occur in multiple gestations, depending on the co-twin for circulation through anastomoses.

The prevailing pathogenetic theory is that this profound abnormality is the result of very early disorganization of extensive developmental fields, as a result of placental anastomoses between monozygous twins [concordance for gender has been 100%]; it can be thought of as an extreme example of twin to twin transfusion. Earlier ideas about the acardia being a primary defect have not gained much acceptance. In any case, the evidence is in favor of this being a sporadic event, since there has been no report of familial recurrence. Dean and Ceballos11 expressed the view that rapidly growing structures such as the branchial arches, maxilla, and mandible are rudimentary because of the severe loss of blood flow in early development; some acardiac/acephalic fetuses do, however, possess teeth (albeit sometimes in peculiar places and configurations).

Another theory proposed for the origin of this condition is the fertilization of the first polar body12, but this has not gained much attention.

Diagnosis

Careful dissections since the early reports centuries ago have revealed the profound disorganization of multiple organ systems in acardiac fetuses. Only very recently have we been able to study the chromosomal constitution of these rare fetuses; there have been only few reports of aneuploidy, but not many affected fetuses have been studied. A review of 11 cases in which both the acardiac and the surviving twin had karyotypes performed, with two new cases, revealed:

There was a case with 47,XXY in both the acardiac and the survivor, and one with 94,XXXXYY in the acardiac and 47,XXY in the survivor. All the other surviving phenotypically normal co-twins had normal karyotypes¹³. It would appear that profound chromosomal abnormalities may predispose to massive disruption of very early developmental fields, but such disruptions may also occur in the presence of normal karyotype.

It is important to document the karyotype of the surviving twin, since some chromosomal abnormalities may not produce obvious malformations, but still have important implications for the prognosis. Whenever discovery of the problem occurs, an effort should be made to obtain karyotypes of both twins (that is, prenatally or at delivery). Modern ultrasonographic examination of most pregnancies provides the hope of relatively early detection of an acardiac twin^14-15.

Management

The management of such cases is a thorny issue, since retention of a dead fetus presents a risk to the survivor. Either the development of heart failure, or the effects of products of necrosis, can injure or kill the normal co-twin. Selective delivery is difficult, but there have been reports of success ^1,16. Earlier suggestions for medical management of fetal heart failure by maternal administration of oral digoxin¹⁷, and ligation of the acephalic fetus" umbilical cord¹⁸ are less aggressive and of uncertain efficacy, but were favored by those who published the cases and since then by others ¹⁹. Still, if the acardiac is quite small the option for conservative watch and wait approach may be sufficient²⁰; such would probably not be the case in the event of prenatal detection of an acardiac as large as the present one (where a favorable outcome for the pump twin is surprising).

The problem of determining whether the acardiac twin is alive or dead has received some attention²⁴. The tissues of the fetus are kept alive by their essentially parasitic relationship to the co-twin, whose heart perfuses both bodies. Yet the acardiac twin has no possibility of survival once that special relationship has ended; this is true even aside from the acardiac status, since complete acephaly also means both absence of most of the central nervous system (equivalent to anencephaly), and of the upper digestive tract.

References

1. Robie GF, Payne GG, Morgan MA: Selective delivery of an acardiac, acephalic twin. New Engl J Med 320:512-513, 1989.

2. Benedetti A: De Morborum a Capite de Pedis Signis. Venice: Lucaeantonii, 1533.

3. Schedel: Incunabula collection at Countway Medical Library, Harvard University Medical School, 1493.

4. Warkany J: Congenital Malformations. Chicago: Year Book, 1971.

5. Gillim DL, Hendricks CH: Holoacardius: review of the literature and a case report. Obstet Gynecol 2:647-653,1953.

6. Mappo M: Historia medica de Acephalis. Argento: JF Spoor, 1687.

7. Herholdt JD: Beschreibung sechs menschlicher Missgeburten. Kopenhagen: HJ Bingschen, 1830.

8. Geoffroy-St. Hillaire I: Histoire generale et particuliere des Anomalies de l"organisation chez l"homme et les animaux. Paris: JB Bailliere, 1832.

9. Elben E: Tabulae ad dissertationem anatomico physiologicam de Acephalus sive Monstris Corde Carentibus. Berlin, 1821.

10. Moore TR, Gale S, Benirschke K: Perinatal outcome of forty-nine pregnancies complicated by acardiac twinning. Am J Obstet Gynecol 163:907-912,1990.

11. Dean D, Ceballow R: Congenital malformation: dental features of acardia - case report. J Oral Med 40:106-107,1985.

12. Bieber FR, Nance WE, Morton CC, Brown JA, Redwine FO, Jordan RL, Mohanakumar T: Genetic studies of an acardiac monster: evidence of polar body twinning in man. Science 213:775-777,1981.

13. Moore CA, Buehler BA, McManus BM, Harmon JP, Mirkin LD, Goldstein DJ: Acephalus-acardia in twins with aneuploidy. Am J Med Genet Suppl 3:139-143,1987.

14. Reuhland RG, O"Leary JA, Ferrell RE: The holoacardius acephalus twin: prenatal diagnosis. Am J Perinatol 3:33-34,1986.

15. Gibson JY, D"Cruz CA, Patel RB, Palmer SM: Acardiac anomaly: review of the subject with case report and emphasis on practical sonography. J Clin Ultrasound 14:541-545,1986.

16. Ginsberg NA, Applebaum M, Rabin SA, Caffarelli MA, Kuuspalu M, Daskal JL, Verlinsky Y, Strom CM, Barton JJ: Term birth after midtrimester hysterotomy and selective delivery of an acardiac twin. Am J Obstet Gynecol 167:33-37,1992.

17. Simpson PC, Trudinger BJ, Walker A, Baird PJ: The intra-uterine treatment of fetal cardiac failure in a twin pregnancy with an acardiac, acephalic monster. Am J Obstet Gynecol 147: 842-844,1983.

18. Platt LD, DeVore GR, Bieniarz A, Brenner P, Rao R: Antenatal diagnosis of acephalus acardia: a proposed management scheme. Am J Obstet Gynecol 146:857-859,1983.

19. Quintero RA, Reich H, Puder KS, Bardicef M, Evans MI, Cotton DB, Romero R: Brief report: umbilical-cord ligation of an acardiac twin by fetoscopy at 19 weeks of gestation. New Engl J Med 330:469-471,1994.

20. Gross B, Petrikovsky B, Lane E: Twin, acardiac, amorphus. The Fetus 4:19-22,1994.

21. Fusi L, Fisk N, Talbert D, Gau G, Rodeck C: When does death occur in an acardiac twin? Ultrasound diagnostic difficulties. J Perinat Med 18:223-227,1990.