A complex tetralogy of Fallot case with an unusual cluster of malformations diagnosed by multiple prenatal ultrasound views

Background Tetralogy of Fallot (TOF) is a complex congenital anomaly with a wide variety of prenatal presentations beyond the core malformations, creating diculty in prenatal diagnosis, prognosis, and perinatal management. Indeed, TOF should be considered the ‘complex’ of Fallot. Case presentation Through a series of precise prenatal ultrasound views, we describe a rare case of complex TOF with multiple malformations including main pulmonary artery atresia, left ductus arteriosus connecting subpulmonary arteries to the left innominate artery, and a right aortic arch with mirror image branching. The prenatal diagnosis and all ultrasound ndings were conrmed by autopsy. Conclusions Tetralogy of Fallot (TOF) is a complex congenital anomaly with various branches of blood vessels. A set of standard views plus additional views (the upper chest coronal view) are required for prenatal diagnosis of complex TOF.


Introduction
Complex tetralogy of Fallot (TOF) is classi ed into three main types, TOF with pulmonary artery atresia (PA), TOF with absence of pulmonary valve, and TOF with atrioventricular septal defect [1][2][3] . However, complex TOF is associated with many additional vascular malformations aside from these core features 3 . Some of these associated malformations are extremely rare, such as abnormal connections to the ductus arteriosus. We describe a rare case of complex TOF (pulmonary atresia type) with PA, left ductus arteriosus connecting subpulmonary arteries to the left innominate artery, and a right aortic arch with mirror image branching, revealed by a precise sequence of prenatal ultrasound views.

General information
A 41-year-old pregnant female (26 + 1 weeks gestational age) who was in good health and had no personal or family history of birth malformations or genetic disorders received an X-ray examination for a cold during early pregnancy. Anatomical structural screening of the fetus revealed cardiac structural abnormalities but no extracardiac abnormalities. Detailed fetal echocardiography was then performed with a GE 10 Ultrasound (Tiefenbach, Austria) equipped with a 2 − 7 MHz convex probe (GE).

Ultrasonographic ndings
Four-chamber views revealed a 0.59-cm discontinuity of the interventricular septum and color Doppler ow imaging (CDFI) demonstrated a bidirectional shunt at this ventricular septum defect.
A view of left ventricular out ow showed that the ventricular septal defect was of the perimembranous type. The dilated aorta overrode the ventricular septal defect by 50% (Fig. 1). A right ventricular out ow view was not acquired.
Three-vessel and three-vessel tracheal views could not visualize the main pulmonary artery but did reveal a con uence of dilated right and left pulmonary arteries. The ductus arteriosus also was not found at the normal anatomical location. The aortic arch was positioned to the right of the trachea. The rst branch of the aortic arch was the dilated left innominate artery running left and anterior to the trachea. The second branch was the right common carotid artery, following by the right subclavian artery. On CDFI, reverse bidirectional blood ow was detected in the subpulmonary arteries (Fig. 2).
The upper chest coronal view showed a dilated vessel to the left and anterior to the trachea originating from the subpulmonary arteries and further connected to the dilated left innominate artery. Pulse wave Doppler (PW) demonstrated that this dilated artery was the ductus arteriosus and CDFI revealed reversed blood ow in the ductal arch (Fig. 3).
The nal ultrasound diagnosis was complex TOF with main pulmonary atresia, right aortic arch with mirror image branching, and left ductus arteriosus between the subpulmonary arteries and left innominate artery.

Discussion
Asymmetric fusion of the artery bulbar and truncal ridges resulting in anterosuperior displacement of the outlet septum generates tetralogy of Fallot 2 . The anterosuperior deviation of the outlet septum relative to the rest of the ventricular septum causes an anterior misalignment type of ventricular septal defect, pulmonary obstruction, overriding or dextroposition of the aorta, and right ventricular hypertrophy 7 . In addition to the main features, TOF is associated with other structural abnormalities 3 , such as a right aortic arch 5 , a deviated cardiac axis, an aberrant subclavian artery, and an absent ductus arteriosus 7 .
Pulmonary atresia (PA) type accounts for 30% of TOF cases. In pulmonary atresia, the subpulmonary artery is reperfused by the ductal arch or by the somatopulmonary collateral from the descending aorta. This case of TOF with PA featured a right aortic arch with left ductus arteriosus connected between the dilated left innominate artery and subpulmonary arteries. A recent study reported prenatal TOF detection rates of only 30-60% 1 , and differentiation of TOF subtypes with unusual associated malformations is even more challenging 1,7 . Ignorance of this potential connection between dilated left innominate artery and subpulmonary arteries via left ductus arteriosus can lead to misdiagnosed as absent ductus arteriosus.
In the current case, we suspected that the ductus arteriosus may exist but with abnormal connectivity based on detection of dilated subpulmonary arteries with reversed bidirectional blood ow. Furthermore, a right aortic arch with mirror image branching is usually associated with left ductus arteriosus connected to the descending aorta or the left innominate artery. Subsequently, we found that the dilated left innominate artery originated at the aorta arch, providing a rationale to scan the upper chest in the coronal plane to look for the linkage between dilated left innominate artery and subpulmonary arteries. Finally, the ductal arch connected between the dilated left innominate artery and subpulmonary arteries was detected, thus avoiding prenatal misdiagnosis as absent ductus arteriosus, and the pulse wave Doppler (PW) demonstrated the expected ow pattern. The correct structural assessment of the aortic arch, the branches of the aortic arch, ductus arteriosus, and pulmonary artery by prenatal ultrasound could aid in fetal prognosis of complex TOF 4 .
According to the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) guidelines, a set of standard views plus additional views (the upper chest coronal view) are required for diagnosis of complex TOF. Complete acquisition of these standard views combined with careful analysis could reduce the risk of prenatal misdiagnosis and be useful for pregnancy counseling.

Declarations
Ethical Approval and Consent to participate Prenatal ultrasound screening was conducted according to the Maternal and Infant Health Care Law of China. Written informed consent was obtained from all pregnant women before prenatal ultrasound screening. The study was approved by the Ethics Committee of Chengdu Women's and Children's Central Hospital.

Consent for publication
Above all consents could be published.

Availability of data and materials
All data and materials were available.
Funding: This research did not receive any speci c grant from funding agencies in the public, commercial, or not-for-pro t sectors.

Authors' contributions
Yun Wu is the rst author who wrote the case report and analyzed the case.
Liuying Zhou is the co-rst author provided case pictures and analyzed the case.