Address correspondence to Luís Flávio Gonçalves, MD, Vanderbilt University, De­partment of Radiology, 21^st and Garland, Nashville, TN 37323-5316, Ph: 615-343-0595, Fax: 615-343-4890

Synonyms: ADAM complex (amniotic deformities, adhesion, mutilation), amniotic band sequence, amniotic disruption complex, annular grooves, congenital amputation, congenital constricting bands, Streeter bands, transverse terminal defects of limb¹, aberrant tissue bands, amniochorionic mesoblastic fibrous strings, amniotic bands².

Definition: Amniotic band syndrome is a set of congenital malformations ranging from minor constriction rings and lymph­edema of the digits to complex, bizarre multiple congenital anomalies that are attributed to amniotic bands that stick, entangle and disrupt fetal parts.

Prevalence: The prevalence for live births is 7.7:10,000¹; for spontaneous abortions it can be as high as 178:10.000³. M1:F1.

Etiology: Unknown. Some authors have suggested a teratogenic effect in some cases^4,5.

Pathogenesis: Rupture of the amnion in early pregnancy leads to entrapment of fetal structures by “sticky” mesodermic bands that originate from the chorionic side of the amnion, followed by disruption^3,6,7. This theory has been contested recently based on clinical and experimental data (see text)^4,5.

Resulting anomalies: Constriction rings around the digits, arms and legs; swelling of the extremities distal to the point of constriction; amputation of digits, arms and legs; asymmetric facial; cephalocele; anencephaly; multiple joint contractures; pterygium; clubfeet, clubhands and pseudosyndactyly; microph­thal­mia, uveal coloboma, corneal metaplasia and unilateral chorio­retinal lacunae^3,7-10.

Differential diagnosis: Amniotic fold¹¹, body-stalk anomaly.

Prognosis: Lethal when extensive, but mild forms can be found in term deliveries³.

Recurrence risk: No recurrence expected, except in rare sporadic familial cases that have been reported in association with epi­dermolysis bullosum and Ehler-Danlos syndrome^1,12,13.

Management: Depends on the extent of the anomalies.

MESH Amniotic band syndrome ICD9 658.8 CDC 658.800 MIM 31710 POS 3631 BDE 0874

Introduction

“In 1937 I observed an amazing sac. While viewing the interior of the distended fetal sac it was seen that the amnion was in the form of an open, globular pocket surrounding the placental attachment of the umbilical cord. The amnion had obviously been ruptured at about midterm pregnancy. There was no damage to the chorionic sac, in which the fetus had continued to live. There were multiple fibrous strands issuing from the surface of the amnion sac as well as from the amnion-denuded chorion which had contained the fetus. Subsequently, a somewhat similar situation was observed in another distended fetal sac. Could these strands injure the fetus? In both of these instances, the respective fetus was found to have sustained malformations post­ulated by the condition of the fetal membranes⁷...”

Richard Torpin, 1968

With these words, Richard Torpin begins the description of a lifelong work that shone much light on the pathogenesis of one of the most intriguing and dramatic malformations of the fetus. Amniotic band syndrome has been studied since the time of Hippocrates and Aristotle. Speculations regarding the etiology of the syndrome over the years ranged from maternal impressions, focal developmental errors in the formation of limb connective tissue and finally to the rupture of the amnion and entrapment of fetal parts by the mesodermic strands that emanate from the chorionic side of the amnion⁷. Yet, many questions are unanswered:

·         What causes the rupture of the amnion ?

·         What causes the internal anomalies observed with the syndrome ?

·         How to explain the cases of “amniotic band syndrome” with a histologically normal and intact amniotic lining ?

·         Why are monozygotic twins more often affected than dizygotic?

We report a case of amniotic band syndrome affecting one sibling of a pair of monozygotic twins.

Case report

A 21-year-old woman G­4P1111 was referred for ultrasound examination at 16 weeks. Her past obstetrical history was remarkable for one spontaneous abortion, one stillbirth at 24 weeks and the spontaneous vaginal delivery of a healthy term infant.

Ultrasound examination demonstrated a twin pregnancy with a single posterior placenta and two amniotic cavities separated by a membrane. In the left gestational sac, amniotic bands attached to multiple sites of the fetus (fig. 1-4).

Figure 1: Right frontal cephalocele.

Figure 2: Strands of amnion (arrows) are attached and move with the forehead.

Figure 3: A large facial cleft (white arrow) extends to the lens of the left eye (black arrow) (compare to fig. 5).

Figure 4: Amniotic bands attach to the lower abdomen and disrupt it.

Multiple anomalies were observed including: hydrocephalus, a right frontal encephalocele (fig. 1-2), a facial cleft extending towards the right eye (fig. 3); a lower abdominal wall disruption with multiple loops of bowel floating freely in the amniotic fluid (fig. 4); bladder exstrophy; and a single right umbilical artery. The right-sided twin appeared normal.

The patient opted to terminate the pregnancy. After receiving several doses of Prostin, she delivered a 123g fetus that was noted to have multiple anomalies and a 126g morphologically normal male infant. She had a retained placenta and required a D&C.

Due to the D&C procedure, the placenta was sent, in fragments, to autopsy. A dividing membrane could not be identified and no umbilical cord could be seen attached to any of the placental fragments. The only available umbilical cord segment had three vessels. The autopsy (fig. 5) demonstrated a right frontal cephalocele, severe mid­line facial deformities including cleft lip and palate, no identifiable eye structures, low set ears, a large abdominal wall defect in the lower abdomen containing bowel and liver, imperforate anus, no external genitalia, bilateral testes within the abdomen, and a gross amputation of the left lower leg below the knee joint. The other twin was normal.

Figure 5: The fetus after delivery. Note the right frontal cephalocele, facial cleft toward the left eye, lower abdominal wall disruption and amputation of the left leg, below the knee.

Discussion

Prevalence

The prevalence of amniotic syndrome among live births is estimated to be around 7.7:10,000¹.Among abortuses it may be as high as 178:10,000³. It affects males and females in the same proportion.

Recurrence risk

Most of the cases are sporadic, with no recurrence in siblings or children of affected adults². However, there are some reports of amniotic band syndrome among families with collagen disorders, more specifically Ehler-Danlos syndrome¹³.

Consequential anomalies

The anomalies associated with amniotic band syndrome are listed in Table 1^2-5,7,15-17.

Table 1: Consequential anomalies

Diagnosis

The most common finding in amniotic band syndrome is constriction rings of the fingers and toes¹⁸. It occurs in seventy-seven percent of fetuses with multiple anomalies³. The association of the abnormalities described above should be regarded as strong evidence and raise the suspicion of amniotic band syndrome. The visualization of amniotic bands attaching to a fetus with restriction of motion is diagnostic of the condition, precluding the need for fetal karyotype^3,16. However, the visualization of amniotic bands or sheets in the absence of fetal deformities should by no means lead to the diagnosis of amniotic band syndrome, since several types of membranes (such as folds of amnion or extra-amiotic pregnancies³⁵) may be seen in normal pregnancies¹⁶. The diagnosis is confirmed at autopsy by the demonstration of chronic rupture of the chorion in histologic sections of the placenta.

In our case, the diagnosis was established prenatally by the association of a right frontal cephalocele, asymmetrical facial cleft, and a lower abdominal wall disruption with multiple loops of bowel floating freely in the amniotic fluid. Furthermore, the amniotic bands were clearly visualized attaching to the defects. Although only placental fragments were available for autopsy, our prenatal findings demonstrate a monochorionic placentation. The external genitalia were absent on the affected twin, but the abdominal testis confirmed the sex.

There are 18 published reports of amniotic band syndrome in twins (excluding the present case). Fourteen were reviewed by Lockwood et al; all were monozygotic, and in four instances both twins were affected⁴. In another case of monozygotic twins and amniotic band syndrome, one twin was abnormal but the unaffected twin survived¹⁹. Two reports describe the association of amniotic band syndrome and an acardius amorphus twin^20,21. A recent report documents the occurrence of amniotic band syndrome in one twin of a dizygotic pregnancy²².

Etiology

The etiology is unknown. There have been reports associating amniotic band syndrome with maternal trauma, oophorectomy during pregnancy²³, intrauterine contraceptive device²⁴ and amniocentesis^25-27, but these are clearly a minority. There are case reports in families with connective tissue disorders (Ehler-Danlos syndrome)¹³.

Since seventeen of the eighteen cases of amniotic band syndrome in twins published in the literature were in monozygotic twins, and since monozygotic twinning is theoretically the result of a teratogenic stimulus, a teratogenic insult might be implicated as causing the disorder^4,5.

Table 2: Anomalies associated with amniotic band syndrome: explained and unexplained by the early amnion rupture theory.

Pathogenesis

The cause of the malformations in amniotic band syndrome remains controversial.

Endogenous theory

For many years, the defects associated with amniotic band syndrome were thought to result from focal developmental errors in the formation of limb connective tissue¹⁴.

Exogenous theory

Torpin studied 400 cases of amniotic band syndrome. He believed that rupture of the amnion without rupture of the chorion leads to transient oligohydramnios due to loss of amniotic fluid through the initially permeable chorion. The fetus would pass from the amniotic to the extraembryonic coelom through the defect. The contact of the fetus with "sticky†mesoderm on the chorionic surface of the amnion would lead to entanglement of the fetal parts and skin abrasions. Entanglement of the fetal parts would cause constriction rings and amputations, whereas skin abrasions would lead to disruption defects such as cephaloceles. Furthermore, swallowing of the bands would cause asymmetric clefts on the face^4,7,28.

Vascular theory

Lockwood et al. contest the exogenous theory based on clinical and experimental evidence⁵. Among the clinical evidence against the exogenous theory are:

·         the high prevalence of internal visceral anomalies and anomalies not readily explicable by the amniotic disruption sequence as proposed by Torpin (see Table 2),

·         cases of amniotic band syndrome with a histologically normal and intact amniotic lining

·         the frequent finding of disruptive defects in fetuses not in contact with bands.

Experiments injecting vasoactive substances in rats have reproduced external and internal features of amniotic band syndrome without disruption of the amnion^29,30. Furthermore, histologic evidence confirms that hemorrhages precede limb constrictions, amputations, clefts and clubfoot in the rat model³⁰. The pathogenesis would involve damage of the mesenchymal and endothelial cells of the superficial vessels of the embryo and the amnion, with disruption of epiblastic cells and secondary limb amputation, constriction bands, cephaloceles, syndactyly, clubfoot and clubbed hands³¹. Amniotic band formation would be a late and secondary event, analogous to adhesion formation.

Unfortunately, the single umbilical artery visualized in the prenatal sonogram could not be confirmed during autopsy, because of the D&C procedure. This finding is consistent with the arguments of Lockwood et al. and is difficult to explain solely on the exogenous theory.

Differential diagnosis

Ammiotic folds

Amniotic folds are recognized by prenatal ultrasonography as reflecting membranes floating freely in the amniotic fluid. They have been reported in patients who had instrumentation of the uterine cavity resulting in intrauterine scars or adhesions. Randel et al. hypothesize that the "adhesions resulting from such instrumentation and stretching across the endometrial cavity could cause the amnion and chorion to grow around the scar‹¹. The membrane is thick, with two layers of amnion and two layers of chorion. It has a free edge and does not attach to the fetus, so the baby can move independently of the membrane. Occasionally a vessel can be seen running at the free edge. The fetus is morphologically normal.

Short umbilical cord syndrome

Also known as limb-body wall complex or body stalk anomaly, this is a complex set of disruptive abnormalities having in common the failure of closure of the ventral body wall. Although some of the features are similar to those of the amniotic band syndrome, there are distinctive characteristics: marked scoliosis, evisceration of abdominal contents into the extraembryonic coelom, and a shortened umbilical cord³². Limb amputations are not typically found in this syndrome, which is predominently limited to the abdominal wall.

Extra-amniotic pregnancy

Extra-amniotic pregnancy is a rare condition that is explained by a mechanism similar to the exogenous theory of the amniotic band syndrome: a rupture of the amnion, with development of the fetus in the extraembryonic coelom. The rupture of the amnion is supposed to occur later, when the amnion and chorion have lost their "stickyness^"35.

Prognosis

The prognosis varies depending on the associated anomalies. It can be quite good for infants with only minor constriction rings and lymphedema of the digits. Children with amputations of the limbs may require reconstructive or plastic surgery and prosthesis. Good results have been reported in the literature using Ombredanne"s two-stage operation, or serial excision and repair with Z-plasties^33,34. There is normal life expectancy for these cases. The syndrome is lethal for the severe forms with multiple associated anomalies^2,3.

Management

The prenatal management of amniotic band syndrome will depend largely on the type and extent of malformations. Minor and isolated constriction rings are less likely to be diagnosed prenatally. Hence, the approach to counseling will vary from case to case. For the severe forms, the option for pregnancy termination can be offered.

References

1. Buyse ML: Birth defects encyclopedia. Blackwell Scientific Publications, Cambridge, MA, 1990.

2. Seeds JW, Cefalo RC, Herbert WNP. Amniotic band syndrome. Am J Obstet Gynecol 144:243, 1982.

3. Nyberg DA, Mahony BS, Pretorius DH. Diagnostic ultrasound of fetal anomalies. Year Book Medical Publishers, Littleton, Mass. 1990.

4. Lockwood C, Ghidini A, Romero R, et al. Amniotic band syndrome in monozygotic twins: prenatal diagnosis and pathogenesis. Obstet Gynecol 71:1012-5, 1988.

5. Lockwood C, Ghidini A, Romero R, et al. Amniotic band syndrome: reevaluation of its pathogenesis. Am J Obstet Gynecol 160:1030-3, 1989.

6. Dimmick JE, Kalousek DK. Developmental pathology of the embryo & fetus. JB Lippincott, Philadelphia, 1992.

7. Torpin R. Fetal Malformations Caused by Amnion Rupture During Gestation. Springfield, Il:Charles C Thomas, pp 1-76, 1968.

8. BenEzra D, Frucht Y. Uveal coloboma associated with amniotic band syndrome. Can J Ophthalmol 18:136-8, 1983.

9. BenEzra D, Frucht Y, Paez JH, et al. Amniotic band syndrome and strabismus. J Pediatr Ophthalmol Strabismus 19:33-6, 1982.

10. Hashemi K, Traboulsi E, Chavis R, et al. Chorioretinal lacuna in the amniotic band syndrome. J Pediatr Ophthalmol Strabismus 28:238-9, 1991.

11. Randel SB, Filly RA, Callen PW, et al. Amniotic sheets. Radiology 166:633-6, 1988.

12. Marras A, Dessi C, Macciotta A. Epidermolysis bullosa and amniotic bands. Am J Med Genet 19;815, 1984.

13. Young ID, Lindenbaum RH, Thompson EM, et al. Amniotic band syndrome in connective tissue disorders. Arch Dis Child 60:1061-3, 1985.

14. Streeter GL. Focal deficiency in fetal tissues and their relation to intrauterine amputation. Contrib Embryol 33:41, 1930.

15.Mahony BS, Filly RA, Callen PW, et al. The amniotic band syndrome: antenatal sonographic diagnosis and potential pitfalls. Am J Obstet Gynecol 152:63-8, 1985.

16. Burton DJ, Filly RA. Sonographic diagnosis of the amniotic band syndrome. AJR 156:555-8, 1991.

17. Hunter AGW, Carpenter BF. Implications of malformations not due to amniotic bands in the amniotic band sequence. Am J Med Genet 24-691:700, 1986.

18. Fiedler JM, Phelan JP. The amniotic band syndrome in monozygotic twins. Am J Obstet Gynecol 14:863-4, 1983.

19. Shih TY, Liu YJ, Lin YZ, et al. Amniotic band disruption complex: report of one case in twins. Acta Paediatr Sin 32:115-21, 1991.

20. Calame JJ, van-der-Harten JJ. Placental teratoma or acardius amorphus with amniotic band syndrome. Eur J Obstet Gynecol Reprod Biol 20:265-73, 1985.

21. Draeger A, Nerlich A. Amniotic band syndrome associated with an acardiac malformation in a twin

pregnancy. A propos of a case. Ann Pathol 317-20, 1988.

22. Gilbert WM, Stanley ED, Kaplan C, et al. Morbidity associated with prenatal disruption of the dividing membrane in twin gestaions. Obstet Gynecol 78:623-30, 1991.

23. Tanaka O, Koh T, Otani H. Amniogenic band anomalies in a fifth-month fetus and in a newborn from maternal oophorectomy during early pregnancy. Teratology; 33:187-93, 1986.

24. Csecsek K, Szeifert GT, Papp Z. Amniotic bands associated with early rupture of amnion due to an intrauterine device. Zentralbl Gynakol 109:378-41, 1987.

25. Kohn G. The amniotic band syndrome: a possible complication of amniocentesis. Prenat Diagn 8:303-5, 1987.

26. Ashkenazy M, Borenstein R, Katz Z, et al. Constriction of the umbilical cord by an amniotic band after midtrimester amniocentesis. Acta Obstet Gynecol Scand 61:89-91, 1982.

27. Lage JM, VanMarter LJ, Bieber FR. Questionable role of amniocentesis in the etiology of amniotic band formation. A case report. J Reprod Med 33:71-3, 1988.

28. Higgenbottom MC, Jones KL, Hall BD. The amniotic band disruption complex: timing of amniotic rupture and variable spectra of consequent defects. J Pediatr 95:544-549, 1979.

29. Herva R, Karkinen-Jaaskelainen M. Amniotic adhesion malformation syndrome: fetal and placental pathology. Teratology 29:11, 1984.

30. Kino Y. Clinical and experimental studies of the congenital constriction band syndrome, with an emphasis on its etiology. J Bone Joint Surg 57A:636, 1987.

31. Clavert JM, Clavert A, Issa WN, et al. Experimental approach to the pathogenesis of the anomalies of amniotic disease. J Pediatr Surg 15:63, 1980.

32. Van Allen MI, Curry C, Walden L. Limb-body wall complex II: Limb and spine defects. Am J Med Genet 38:549-565, 1987.

33. Dal Monte A, Soncini G, Calderoni P, et al.: The treatment of congenital constricting bands by Ombredanne"s two stage operation. Review of 13 cases. Ital J Orthop Traumatol 9:351-5, 1983.

34. Upton J, Tan C. Correction of constriction rings. J Hand Surg Am 16:947-53, 1991.

35. Jeanty, P, Laucirica R, Luna SK: Extra-amniotic pregnancy: a trip to the extraembryonic coelom. J Ultrasound Med 9:733-6, 1990.