NORD gratefully acknowledges Lewis B. Holmes, MD, Emeritus Chief, Genetics Unit, MassGeneral Hospital for Children, and Professor of Pediatrics, Harvard Medical School, for assistance in the preparation of this report.
Amniotic band syndrome is a well-known condition potentially associated with a variety of different birth defects. It is important to note that no two cases of amniotic band syndrome are exactly alike and that the associated symptoms are highly variable. The severity of amniotic band syndrome can range from a single, isolated finding to multiple, disfiguring complications. The arms and legs are most often affected. The head and face and, in some cases, various internal organs can also be affected. The exact cause of amniotic band syndrome is unknown and controversial. Two main theories have been proposed to explain the development of the disorder. One theory attributes the disorder to causes that arise internally within the fetus (intrinsic theory); the other theory attributes the disorder to causes acting upon the fetus externally (extrinsic theory). It is likely that both internal and external factors can cause amniotic band syndrome, and that the cause of the disorder in one infant may be different from the cause in another infant.
The symptoms associated with amniotic band syndrome vary greatly from one infant to another. Some infants develop only mild complications; others develop severe and even life-threatening complications. Because no two infants are affected in exactly the same way and because the symptoms can vary so greatly, affected infants will not have all of the symptoms discussed below and each individual case will be different. It seems likely that the amniotic band syndrome can develop at any point during the first 20 weeks of pregnancy. Generally, the most severe complications occur when amniotic band syndrome develops early in the first trimester.
Several different patterns have been identified with amniotic band syndrome. The three most common patterns are amniotic band syndrome characterized by one or more limbs being affected; the limb-body-wall complex; and amniotic band syndrome characterized by abnormalities of the head and face (craniofacial abnormalities), certain birth defects of the brain and spinal cord (neural tube defects) and serious malformation of the arms and legs.
Most infants with amniotic band syndrome have some form of deformity of the arms and legs or fingers and toes. One or more limbs may be affected. Upper limbs are affected more often than lower limbs. In some cases, one limb or one hand or foot may be the only symptom of the disorder. Specific symptoms can include certain fingers or toes that are abnormally short, absence of the end (distal) portion of one or more fingers and toes, and/or webbing (fusion) of fingers or toes (syndactyly). Some infants may have bands of tissue (constriction bands) that encircle, entangle and/or gradually constrict certain fetal areas. These bands can cause superficial or slight depressions or grooves (constriction rings) that encircle a limb or digit, but do not constrict it enough to damage the limb or digit. Therefore, despite the presence of this band or ring of tissue, the end (distal) portion of the limb or digit retains its normal size and function. In some cases, strands of tissue are attached to the ends of the fingers.
Another pattern associated with amniotic band syndrome is referred to as limb body wall complex. Affected infants have defects of the abdominal wall that occur in association with defects of the arms and legs and other abnormalities. Infants usually have protrusion of a portion of the brain and its surrounding membranes (meninges) through the skull defect (encephalocele), facial clefts, protrusion of the viscera (the soft internal organs of the body including those found in the abdominal or chest cavities) through a fissure in the abdominal wall (abdominoschisis) or the chest wall (thoracoschisis), and a variety of defects affecting the arms and legs. Additional abnormalities can occur in infants with limb body wall complex.
A third pattern associated with amniotic band syndrome involves craniofacial abnormalities such as incomplete closure of the roof of the mouth (cleft palate), a groove in the upper lip (cleft lip), facial clefts, extremely small, underdeveloped eyes (microphthalmia), narrowing of the nasal passages (choanal atresia), and malformations affecting the size and shape of the skull. In severe cases, neural tube defects such as malformation or absence of portions of the brainstem and spinal cord may occur (anencephaly). Craniofacial abnormalities and neural tube defects occur along with serious complications of the arms and legs called terminal transverse limb deficiencies. In such cases, affected infants may be missing a portion or all of a limb, ranging from one finger or toe to an entire arm or leg.
The causes and underlying mechanisms that cause amniotic band syndrome are complex and controversial. Several different theories have been proposed to explain the complex mechanisms that underlie amniotic band syndrome. The two main theories are known as the extrinsic theory and the intrinsic theory. The extrinsic theory states that amniotic band syndrome occurs due to factors found outside of the fetus (externally); the intrinsic theory states that amniotic band syndrome occurs due to factors found within the fetus (internally).
The extrinsic theory for the development of amniotic band syndrome is that strands of tissue separate from the inner layer (amnion) of the amniotic sac. The amniotic sac is the thin membrane that completely surrounds an embryo or developing fetus (amniotic sac). The sac contains a liquid (amniotic fluid), which supports, cushions and protects a developing fetus. The amniotic sac is composed of two main layers – the outer layer is called the chorion and the inner layer is called the amnion.
According to this theory, amniotic band syndrome occurs when the inner layer (amnion) of the amniotic sac ruptures or tears, exposing the fetus to strands of fibrous tissue that may float freely in the amniotic fluid or remain partially attached to the amniotic sac. These bands of tissue can disrupt the normal development of an embryo or fetus. The bands of tissue can wrap around or entangle (constrict) the fingers, toes, arms, legs and other parts of the developing fetus as when a rubber band had been tightly wrapped around an arm or leg or another body part. The symptoms that occur due to amniotic bands depend on the specific part of the body affected by these strands of tissue and how tightly they have wrapped around a body part. If the amniotic bands are still partially attached to the amniotic sac, they may wrap around a fetal body part and tether (anchor) that body part to the amniotic sac. This can restrict movement and proper development of an embryo or fetus.
The intrinsic theory was proposed because some researchers noted that, while the above theory explains some cases of amniotic band syndrome, it is insufficient to explain all cases. The external theory fails to explain why there is an intact amniotic sac in some infants with amniotic band syndrome; why there are a high number of malformations affecting internal organs in some cases; and why some infants have defects of parts of the body not affected by amniotic (constriction) bands.
The intrinsic theory attributes the development of amniotic band syndrome to impaired blood flow (circulation) to specific parts of the developing fetus (vascular disruption or compromise). The exact, underlying cause(s) of impaired blood flow is unknown. In areas where the blood flow is poor, injury occurs to the blood vessel walls of the fetus. This leads to bleeding (hemorrhaging) and tissue loss in the affected areas, which in turn results in the varied symptoms associated with the disorder. The intrinsic theory attributes the presence of constriction bands as a secondary effect of the impaired blood flow and subsequent damage to the fetus. In a 1987 article in the journal, Teratology, Webster, et al. demonstrated this theory of vascular disruption with an intact amnion in animal models.
Damage to the amniotic sac has been implicated as a cause of amniotic band syndrome under the extrinsic theory. The exact reason that the amniotic sac tears or ruptures is not always known and researchers believe that in some cases it may happen as a random occurrence.
In some cases, specific environmental factors have been identified. Researchers have speculated that trauma to the abdominal area during pregnancy may play a role in some cases. Blunt trauma to the placenta has been shown to cause amniotic band syndrome in some cases.
A fewcases were associated with the performance of a diagnostic technique chorionic villus sampling (CVS). This test may be performed early during pregnancy to detect certain problems in a fetus such as chromosomal abnormalities or certain genetic disorders. During the procedure, tissue is removed from the placenta and certain cells called chorionic villi are studied. One estimate of the risk for this occasional risk was 1 in 2,000 CVS procedures.
It has also been reported that intense uterine contractions caused by a drug known as misoprostol (a prostaglandin E1 analogue) has resulted in amniotic band syndrome. Misoprostol is approved by the Food and Drug Administration for the treatment of gastric ulcers. However, the drug has been used to induce abortion. If the pregnancy continues after the use of misoprostol at 6 to 8 weeks of pregnancy, the infant may have the amniotic band syndrome.
The exact cause of impaired fetal blood flow as suggested by the intrinsic theory is unknown. Researchers believe that genetic factors may play a role in some cases of amniotic band syndrome. Some researchers have noted that amniotic band syndrome occurs with greater frequency in first pregnancies, problem pregnancies or premature births. Young women and women of African descent also have higher rates of infants with amniotic band syndrome. Research is ongoing to determine why certain populations have a greater risk of developing the disorder than other populations.
Some recent genetic studies have begun to identify intrinsic, genetic factors that may predispose infants to the development of amniotic band syndrome (genetic predisposition). A genetic predisposition to developing a disorder means that a person carries a gene, or more likely gene(s), for the disorder, but that the disorder is not expressed unless it is triggered or activated under certain circumstances such as particular environmental factors (multifactorial inheritance).
For example, a genetic predisposition to vascular disruption may contribute to the development of amniotic band syndrome in some cases. Two medical journal articles (Hunter, et al. and Carmichael, et al.) have discussed the possibility that genetic factors influence the development of amniotic band syndrome in certain cases.
Although genetic factors are believed to play a role in the development of infants with some cases of amniotic band syndrome, the risk of recurrence in a subsequent child is extremely low. Most cases of amniotic band syndrome whether due to extrinsic or intrinsic mechanisms occur sporadically. Current, ongoing research into the potential intrinsic factors associated with amniotic band syndrome should reveal more about the complex causes and development of the disorder.
Amniotic band syndrome is estimated to occur in anywhere from 1 in 1,200 to 15,000 live births. No gender or ethnic predispositions have been identified with amniotic band syndrome.
Amniotic band syndrome is typically diagnosed at or soon after birth based upon characteristic physical findings. According to some researchers, minimal diagnostic criteria consist of the detection of certain abnormalities of the arms, legs, fingers, and/or toes, i.e., ring-like constriction or amputation defects.
In some cases, the condition may be suspected before birth (prenatally), based upon the results of certain specialized imaging techniques, such as fetal ultrasonography and amniocentesis, which may reveal the characteristic defects. During fetal ultrasonography, reflected high-frequency sound waves are used to create an image of the developing fetus. During amniocentesis, a small, hollow needle is used to draw out a sample of the amniotic fluid for study. In some cases, laboratory testing may detect elevated levels of alpha-feto protein (AFP) in the amniotic fluid surrounding the fetus. Alpha-feto protein, a protein produced by the fetal liver, is excreted in urine into the amniotic fluid. Raised AFP levels may be associated with a number of abnormalities in a developing fetus (e.g., neural tube defects, esophageal atresia, etc.) or may occasionally be present when the fetus is developing normally.
The treatment of infants and children with amniotic band syndrome is symptomatic and supportive. For example, in infants with incomplete development of the lungs and associated respiratory insufficiency, treatment may include oxygen support measures and other supportive therapies as required. Reconstructive surgery or other surgical techniques may be recommended to help correct or repair associated malformations, such as ring-like constrictions of the limbs, webbed fingers and toes, cleft lip or club foot. Physical and occupational therapy may also be necessary to ensure infants can attain the optimal use of affected fingers, toes, arms and legs.
In rare cases, surgery may be performed before birth (fetal surgery) to cut amniotic bands that are tightly constricting and may cause loss of a limb or digit.
Research is currently ongoing to determine whether there are any underlying risk factors such as genetic factors that may make it more likely for amniotic band syndrome to occur. Such research may eventually help to explain the complex causes and development of amniotic band syndrome in many cases.
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