1999-09-26-18 Amniotic band syndrome © Gonçalves www.thefetus.net/
Amniotic band syndrome
Luís Flávio Gonçalves, MD, Philippe Jeanty, MD, PhD
Address correspondence to Luís Flávio Gonçalves, MD, Vanderbilt University, Department of Radiology, 21st 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 cases4,5.
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 disruption3,6,7. 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 lacunae3,7-10.
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 syndrome1,12,13.
Management: Depends on the extent of the anomalies.
MESH Amniotic band syndrome ICD9 658.8 CDC 658.800 MIM 31710 POS 3631 BDE 0874
“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.
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.
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.
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.
The anomalies associated with amniotic band syndrome are listed in Table 12-5,7,15-17.
Table 1: Consequential anomalies
g constriction rings of limbs or digits
g amputation of limbs or digits
g pseudosyndactyly (pseudosyndactyly involves only the distal
portion of the digits, whereas syndactyly includes the base of the
g abnormal dermal ridge patterns
g simian crease
g multiple and asymmetric cephaloceles
g cleft-lip, -palate & -face
g nasal deformities
g asymmetric microphthalmos
g incomplete or absent calcifications of the skull
g rib clefting
g bladder exstrophy
g ambiguous genitalia
g imperforate anus
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 karyotype3,16. 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 twin20,21. A recent report documents the occurrence of amniotic band syndrome in one twin of a dizygotic pregnancy22.
The etiology is unknown. There have been reports associating amniotic band syndrome with maternal trauma, oophorectomy during pregnancy23, intrauterine contraceptive device24 and amniocentesis25-27, 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 disorder4,5.
Table 2: Anomalies associated with amniotic band syndrome: explained and unexplained by the early amnion rupture theory.
Explainable by the exogenous theory
Lacking explanation by the exogenous theory
g Scalp adhesions
g Skull defects
g Cerebellar dysplasia
g Asymmetrical facial clefts
g Absent olfactory bulbs
g Eye disruptions
g Abdominal wall disruptions
g Small foramen magnum
g Migrational defects
g Heterotopic brain
g Constriction rings
g Cardiac anomalies
g Hip dislocation
g Tracheoesophageal fistula
g Sacral rotation
g Renal agenesis
| || |
g Accessory spleens
| || |
g Gallbladder agenesis
| || |
g Malrotation of the gut
| || |
g Single umbilical artery
| || |
g Internal genital malformation
| || |
g Anal atresia
| || |
g Simian creases
The cause of the malformations in amniotic band syndrome remains controversial.
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.
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 face4,7,28.
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 amnion29,30. 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.
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”11. 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 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.
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-plasties33,34. There is normal life expectancy for these cases. The syndrome is lethal for the severe forms with multiple associated anomalies2,3.
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.
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