Prenatal diagnosis of truncus arteriosus with interrupted aortic arch and abnormal limbs due to an umbilical cord amniotic band: rare entities with an unusual association
- Albert Guarque-Rus 1 , 2,
- Lourdes Martín-González 1,
- Linda Grace Puerto-Tamayo 1 and
- Julieta Landeyro 3 , 4
- 1 Department of Obstetrics and Gynecology, Joan XXIII University Hospital, Tarragona, Spain
- 2 Pere Virgili Health Research Institute, Reus, Spain
- 3 Department of Pathology, Joan XXIII University Hospital, Tarragona, Spain
- 4 Department of Pathology, Pius Hospital de Valls, Valls, Spain
- Correspondence to Albert Guarque-Rus; albertguarque@gmail.com
Abstract
Truncus arteriosus, interrupted aortic arch and amniotic band syndrome are rare conditions. We report a case of a 38-year-old pregnant woman who was diagnosed on a routine morphological ultrasound scan with a Van Praagh type A4 persistent truncus arteriosus with an aortic arch interruption type B and abnormal limbs (oedematous left hand, hypoplastic fingers on the right hand and right big toe amputation). Elective termination of the pregnancy was carried out and the pathological examination confirmed all the sonographic findings. Furthermore, an amniotic band parallel to the umbilical cord undetected during the ultrasound scans was revealed, and was entangled around the right hand, left wrist and the umbilical cord, causing strangulation. We present the unusual association of these independent pathologies and emphasise the usefulness of fetal autopsy in all cases of pregnancy termination and abnormal ultrasound findings to make the complete diagnosis.
Background
Congenital heart defects are the most common congenital abnormalities and they represent an important cause of infant morbidity and mortality.1 Nowadays, thanks to the advances in ultrasonography, we can identify most of these complex cardiac malformations in utero.
Truncus arteriosus is a rare congenital cardiac defect in which there is a single cardiac outflow tract for both ventricles. It accounts for 1% of all congenital heart defects. Prenatal diagnosis and follow-up is important due to its frequent association with other cardiac and extracardiac anomalies, one of them being the interruption of the aortic arch.2
The amniotic band syndrome refers to a group of variable congenital anomalies that involve multiple fetal structures.3 It has low prevalence and only a few cases of constriction of the umbilical cord have been reported.
The coincidence of these pathologies is rare, and represented a diagnostic challenge for us.
Case presentation
A 38-year-old Caucasian secundigravida with an unremarkable medical history was referred to our prenatal diagnosis unit for a routine morphological ultrasound scan at 20+2 weeks of gestation. Her obstetric history was significant for a premature delivery at 32 weeks, and the current pregnancy had a correct antenatal care till that point, with an intermediate risk of T21 (1/973) and a low-risk non-invasive prenatal test result.
The ultrasound scan could not be completed due to fetal malposition and we were unable to check the fetal heart; however, the morphological study showed abnormal upper limbs. The left hand had a massive oedema starting from the wrist and the right hand seemed to be severely deformed with hypoplastic digits covering the first to fourth fingers (video 1).
Re-evaluation at 21+0 weeks demonstrated the already known anomalous hands, along with the suspicion of the amputation of the big toe on the right foot (video 1). In view of this finding, we explored the amniotic membranes for the presence of an amniotic band, but no abnormalities were observed on the detailed ultrasound.
The cardiac reassessment showed an eutopic heart with atrioventricular concordance in a four-chamber view with normal cardiac size. Moreover, a subarterial ventricular septal defect with an abnormal single large outflow tract was noted. That truncus arteriosus divided into a smaller ascending aorta with a straight course to the supraaortic branches toward the neck, and a larger pulmonary trunk with two normal sized pulmonary branches connected to the descending aorta via a wide ductus arteriosus. The truncal valve arose from rather the right ventricle and severe truncal valve regurgitation was demonstrated by Doppler ultrasound. Aortic arch was not identified (video 2). These findings were compatible with Van Praagh type A4 persistent truncus arteriosus with aortic arch interruption type B. No other anomalies were detected during the ultrasound scan.
Investigations
Non-invasive prenatal test was performed due to the intermediate risk for T21 (1/973), estimating low risk.
The detailed morphological evaluation scan was performed in two stages due to technical limitations caused by the fetal position.
A detailed echocardiography was performed with a paediatric cardiologist, who confirmed our findings and assessed the parents about the diagnosis and its prognosis.
Amniocentesis for genetic testing with array comparative genomic hybridation was performed to rule out Di George syndrome, CHARGE syndrome or other genetic conditions, without any pathological results.
Exome sequencing was possible to carry out due to our participation in a clinical exome research project (6000 OMIM genes); however, no pathological results were obtained.
Differential diagnosis
Truncus arteriosus can resemble tetralogy of Fallot.2 A correct differentiation is critical for prenatal counselling because the prognosis differs substantially. Retrograde flow through the ductus arteriosus is typically seen in tetralogy of Fallot and the identification of the pulmonary branches from a central arterial trunk indicates the presence of truncus arteriosus. Moreover, tetralogy of Fallot is usually associated with pulmonary stenosis or atresia.
In the aorticopulmonary window, the clinical features of truncus are present but without a ventricular septal defect.2
Up to 40% of cases with truncus arteriosus, and up to 60%–70% of interrupted aortic arch type B are associated with Di George syndrome.2 4 However, despite the observed cardiac defect, we did not find any thymic hypoplasia or aplasia, intrauterine growth restriction, urinary abnormalities, increased nuchal translucency thickness or abnormal amniotic fluid levels. Subsequently, a 22q11 deletion was not found on genetic testing.
CHARGE syndrome is a rare pattern of abnormalities that commonly features conotruncal and aortic arch defects.5 Our case was not associated with retardation of growth or genital and/or urinary defects were not detected. And 67% of cases are due to a mutation of the CHD7 gene in chromosome 8q12.2, not detected in our case.
Due to the association of the cardiac and limbs defects, VACTERL syndrome was considered as well, and even though our case presented a cardiac defect and what could resemble a unilateral radial limb anomaly, no vertebral or renal anomalies, nor anal atresia or traqueoesophagical fistula were detected.
We also contemplated the heart-hand syndromes (type 1 or Holt-Oram syndrome, type 2 or Tabatznik syndrome and type 3 or Spanish type) that are syndromes with heart abnormalities (mostly septal defects) and radial ray limb deformations produced by mutations on TBX5 and TBX3 genes in chromosome 12q24, with normal genetic testing in our case.
TAR (thrombocytopenia with absent radius) syndrome is a congenital disorder characterised by bilateral radial aplasia with normal thumbs and thrombocytopenia, accompanied in 2/3 of cases by an atrial septal defect or a tetralogy of Fallot. This condition involves a mutation of the RBM8A gene in chromosome 1q12, not found in our case.
The diagnostic considerations based on the prenatal imaging included the amniotic band syndrome, but despite distal limb oedema, hypoplastic digits and an amputated toe, we could not find any amniotic band during the ultrasound evaluations.
We also thought about Fanconi anaemia that consists of blood abnormalities with radial ray defects. Despite a severely deformed right hand, it did not seem to us like a radial ray defect.
And finally lymphatic/vascular malformation like lymphangioma, that is a benign malformation due to a dilatation of the cystic lymphatics. It can occur in almost any location, but not usually at distal upper limbs. In Milroy disease, the common presentation is unilateral lower limb lymphoedema.
TREATMENT
Once informed about the severity and poor prognosis of the malformations of their fetus, the parents requested termination of the pregnancy.
Outcome and follow-up
Termination of pregnancy through feticide and induction of labour with vaginal misoprostol took place at 22+3 weeks and a 350 g stillborn female fetus was delivered. The pathological examination showed an amniotic band parallel to the umbilical cord (figure 1) that was unseen during the ultrasound scans. This amniotic band was entangled around both hands and the umbilical cord (figure 2). The strangulation of the left wrist led to the massive distal limb oedema (figure 3). The entanglement of the amniotic band with the right hand was causing constriction that led to the hypoplastic fingers (figure 4). The umbilical cord, that was twisted around the left wrist as well, was also entangled with the amniotic band, causing strangulation (figures 2 and 3). Right foot’s big toe amputation (figure 5) and the truncus arteriosus with the interrupted aortic arch were found as described prenatally (figure 6). Syndactyly between the third and the fourth toes was observed on the right foot (figure 5). No other abnormalities were found on autopsy.
Amniotic band (arrows) originated from and parallel to the umbilical cord that was unseen during the ultrasound. Note the distal end (*) entangled around the right hand, the left hand and the umbilical cord, causing dramatic strangulation (see figure 2).
Entanglement of the amniotic band around the right hand causing constriction that led to the hypoplastic fingers (*). Entanglement around the left wrist (+) causing the constriction that led to the massive oedema of the distal limb ($). Strangulation of the umbilical cord (#) that was twisted around the left wrist.
Palmar view of the left hand with the massive oedema starting from the wrist, including the fingers, caused by the strangulation produced by the amniotic band. Note the umbilical cord twisted around the wrist.
The right hand. (A) Palmar view of the right hand with oedematous first to fouth fingers and only the fifth finger being normal. (B) Lateral view of the left hand where we can see the amniotic band that was compressing the first to fourth digits.
Right foot with big toe amputation (*) and syndactyly between third and fourth toe (+).
The heart. (A) Schematic representation of a Van Praagh type A4 truncus arteriosus. The main common arterial trunk, or truncus arteriosus (TA) arises from a ventricular septal defect (VSD), dividing in a small ascending aorta (AA) with straight course to supraaortic branches (innominate artery, IA; and left common carotid artery, LCCA) and a large common pulmonary trunk (CPT) with two normal size pulmonary branches (right pulmonary artery, RPA; and left pulmonary artery, LPA) connected to the descending aorta (DA) via a patent ductus arteriosus (PDA). Beyond this type B aortic arch interruption, there is the left subclavian artery (LSA) and the descending aorta. (B) Pathological examination with the truncus arteriosus arising predominantly from the right ventricle (RV), and splitting in the AA and the CPT. (C) Specimen dissection cut demonstrating the RV, the VSD, the truncal valves (TV), the CPT branching into the LPA and the RPA, the wide PDA and the branching of the LSA. This figure was illustrated by the one of the authors of the manuscript, AG-R.
DISCUSSION
Congenital heart defects are the most common birth defects and they represent an important cause of infant morbidity and mortality.1 They affect between 4 and 75 per 1000 live births, depending on how they are diagnosed. Nowadays, due to the advances in ultrasonography, we can identify most of these complex cardiac malformations in utero.
Truncus arteriosus is a rare form of congenital heart disease. It accounts for 1% of all congenital heart diseases and is frequently associated with other cardiac and extracardiac anomalies.2 About 10%–20% can be associated with an interrupted aortic arch,6 7 and up to 40% of cases are associated with a 22q11 deletion.4
Truncus arteriosus is caused by a failure in the development of the aorticopulmonary septum, which then leads to a failure of the common trunk division into the aorta and pulmonary artery separately. This congenital heart defect can be classified using the Collett and Edwards or Van Praagh classification systems.8 9
Van Praagh and Van Praagh proposed a classification system for truncus arteriosus, in which truncus is associated with the presence of a ventricular septal defect (type A) and truncus with the absence of a ventricular septal defect (type B). Type A is divided into four subtypes:
Type A1 is characterised by the origin of a short partially separate main pulmonary trunk originating from the truncus arteriosus. It corresponds to Collett and Edwards type I.
Type A2 is defined by pulmonary arteries that originate separately from the common trunk.
Type A3 includes cases with the absence of one pulmonary artery. The other originates from the ductus arteriosus or directly from the descending aorta.
Type A4 is defined by coexistence of truncus arteriosus and interrupted aortic arch.
In our case, we have the common arterial trunk with interrupted aortic arch and associated ventricular septal defect is thus classified as type A4 (figure 6).
Our case also demonstrates the importance of evaluating the aortic arch. Significant hypoplasia of the ascending aorta in this setting should raise suspicion of an interrupted aortic arch.
Interrupted aortic arch is a relatively rare congenital anomaly with a prevalence of approximately two per 100 000 live births. It is characterised by complete anatomic discontinuity between the ascending and descending aorta. Depending on the level of the interruption, there are three types for an interrupted aortic arch:
Type A: the interruption is distal to the left subclavian artery.
Type B: the interruption is between the left common carotid artery and the left subclavian artery.
Type C: the aortic arch is interrupted between the innominate artery and the left common carotid artery.
Type B is the most common form of the condition, and most frequently associated with 22q11 deletion.10 11 This was the type seen in our case, and it is also the most commonly detected prenatally.
The combination of truncus arteriosus and interrupted aortic arch is a rare clinical entity, with very limited case reports of prenatally diagnosed published. Most of them are associated with a high rate of early mortality. Marasini et al 12 described a case of truncus arteriosus with interrupted aortic arch and severe truncal valve regurgitation, that was terminated because the fetus presented a severe hydrops fetalis. Matsumoto et al 13 presented a case of truncus arteriosus and interrupted aortic arch diagnosed prenatally and confirmed by neonatal echocardiography and CT.
In this case, both truncus arteriosus and interrupted aortic arch could be clearly visualised (video 2), as well as tetralogy of Fallot and aorticopulmonary window were ruled out. The genetic test demonstrated no 22q11 deletion.
Truncus arteriosus can also cause the development of congestive heart failure in utero, leading to the features of hydrops. Using colour Doppler during the ultrasound scan, we manifested the insufficient truncal valve with severe regurgitation, which implies high risk of hydrops. However, in our case, we only had the extreme swelling located at the left hand, that was confounding us.
Although the outcomes for truncus arteriosus repair or interrupted aortic arch repair individually are good, Konstantinov et al 14 described that this association significantly increases the mortality risk with an important risk of re-interventions in survivors, poor life quality and in cases of patients with impairment of the functional truncal valve, poor prognosis.
On the other hand, we had also observed the limb abnormalities during the ultrasound scans. The very impressive oedema of the left hand, the severely deformed right hand with hypoplastic fingers (covering the first to fourth digits) and the suspicion of the right big toe amputation made us suspect an amniotic band syndrome. However, amniotic bands can be extremely difficult to see on routine ultrasound scans and after an exhaustive exploration, we could not find any bands coming from the amniotic membrane.
Other possible aetiologies that we considered were lymphatic and vascular malformations, VACTERL syndrome, heart-hand syndromes and radial ray defect syndromes like TAR syndrome or Fanconi anaemia.
After the termination of the pregnancy, the pathological examination showed an amniotic band parallel to the umbilical cord that was unseen during the ultrasound (figure 1). This amniotic band was entangled around the right hand, the left hand and the umbilical cord, causing a substantial constriction (figure 2).
The amniotic band syndrome refers to a group of congenital anomalies involving multiple fetal structures. Amniotic bands entangle embryologically normal fetal structures leading to constriction, disruption and malformation defects, that can range from constriction bands encircling limbs or digits to complex anomaly patterns like limb–body wall complex. The incidence of malformations due to amniotic bands ranges from 1/1200 to 15 000 live births, depending on how it is defined.3
The underlying mechanism of the syndrome is unknown; however, the accepted hypothesis suggests that an early rupture of the amniotic sac leads to the formation of amniochorionic mesodermal bands. These mechanisms are not able to explain all types of malformations, and the type of deformities depends on the time of amniotic rupture.3
Only a few rare cases with constriction of the umbilical cord by an amniotic band have been described.15–22 Chatzigeorgiou et al 19 described a case of intrauterine fetal death at 24 weeks of gestation due to constriction of the umbilical cord by an amniotic band. Niu et al 22 described two cases of early detection of amniotic band syndrome by adhesion between the hand and the umbilical cord at first trimester and intrauterine death during the second trimester, proposing that the fetal hand adhered to umbilical cord with limited activity is an important sonographic sign of early pregnancy suggesting amniotic band syndrome with poor prognosis. Larsen described a demise of a fetus at term due to the strangulation of the umbilical cord by an amniotic band.21 Although almost all of the cases reporting strangulation of the umbilical cord by amniotic bands show fetal deaths, Larciprete et al 20 presented a case of severe fetal distress due to compression of umbilical cord during labour and fortunately, in this case, despite the severe distress, the fetus was born alive and in good health.
Strangulation of the umbilical cord by amniotic bands is very rare and often undetectable. The entanglement in our case (figure 2) gave us the impression that probably could have led to a worse strangulation of the umbilical cord culminating with an intrauterine death at some weeks as described in the literature.
In our case, however, the association of fetal malformations was a diagnostic challenge. It revealed the importance of having a proper prenatal diagnosis and personalised counselling for the family. The parents were informed that this combination of cardiac defects would necessitate medical and surgical intervention in the neonatal period, along with the limb defects of unknown origin. Taking into consideration all the factors, the parents decided to terminate the pregnancy.
In conclusion, the constriction of the umbilical cord by an amniotic band is extremely rare and very hard, if not impossible, to diagnose with prenatal ultrasonography. Its association with a severe cardiopathy, such as truncus arteriosus with interrupted aortic arch, made this case even more unique. And even though we always look for a diagnosis that would include all the findings of the detailed morphological study, we should keep in mind that in rare cases there can be two or more independent pathologies present.
Although the congenital heart defects are diagnosed prenatally, it is important to correlate them with the findings assessed on the fetal autopsy. Therefore, it is indicated in all cases of fetal demise or termination of pregnancy with abnormal ultrasound findings so as to find out the cause and make the complete diagnosis, and should never be missed.
Patient’s perspective
On the day of the second trimester ultrasound, the obstetrician detected problems in my baby’s upper limbs. Realising there was a problem, we were subject to continual testing by the medical team so that we may rule out any genetic conditions. The results were terrifying as they detected even more malformations and we felt it left us with little choice other than terminating the pregnancy. We were heartbroken. I would not expect to feel any comfort from doctors telling us that this case was particularly rare and it has just been bad luck; but I would like to say that even though she was an unborn child, all I feel I have now is a hole that cannot be filled. I only ask why has this happened to her. I really hope in the near future medical advancements prevent this situation from happening to other women and families; I hope they will not have to face what I have lived through.
Learning points
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Truncus arteriosus is an uncommon cardiac anomaly, and when diagnosed prenatally, we must try to identify additional abnormalities, and particularly possible arch anomalies which could influence and worsen the neonatal outcome.
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Strangulation of the umbilical cord by amniotic bands is very rare and often undetectable.
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Although it is unusual to find two or more independent pathologies at once in prenatal diagnosis, we should keep this possibility in mind.
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Fetal autopsy is recommended in all the cases of termination of pregnancy and abnormal ultrasound findings in order to find out the cause and make a complete diagnosis.
Acknowledgments
We want to particularly acknowledge our colleagues: Mònica Ballesteros, Juan Carretero, Mónica López, Marta Jané, Montserrat Inglès and Giula Mackina, who participated in the case. Giula Mackina also did the language editing of the manuscript. And Xavi Pérez did the image editing.
Footnotes
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Twitter @guarque_rus
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Contributors AG-R, LCP-T and LM-G were responsible of the ultrasound examinations and management of the case. JL did the pathological examination. AG-R was responsible for literature research, writing the manuscript and illustration of figure 6. LCP-T, LM-G and JL revised the manuscript. All authors have read and approved the manuscript, and declare that the manuscript is an original work that has not been submitted to another journal or conference.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Competing interests None declared.
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Patient consent for publication Obtained.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.
References
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