Fetal right aortic arch complicated with bilateral ductus arteriosus and isolated left subclavian artery assessed by spatiotemporal image correlation-high-definition live flow imaging: a case description

Introduction

Fetal right aortic arch (RAA) complicated with bilateral ductus arteriosus (BDA) and isolated left subclavian artery (ILSA) is a rare combined malformation involving the aortic arch (AA) branching and ductal system(1). Its anatomical features are as follows: the AA courses along the right lateral aspect of the trachea. It is complicated by the BDA malformation; specifically, the left subclavian artery (LSA) arises from the left pulmonary artery (LPA) via the left ductus arteriosus (LDA) and is perfused by the LPA, whereas the right ductus arteriosus (RDA) connects the main pulmonary artery (MPA) to the aorta. Only three brachiocephalic trunk branches arise from the AA: the left common carotid artery (LCCA), right common carotid artery (RCCA), and right subclavian artery (RSA)(2). Restricted by the inherent limitations of tomographic imaging, prenatal two-dimensional (2D) ultrasound has obvious deficiencies in identifying complex vascular spatial relationships, thus easily leading to missed diagnoses and misdiagnoses(3-5). The combination of spatiotemporal image correlation (STIC) technology and high-definition (HD) live flow mode dynamically acquires fetal cardiac vessel volume data. This can facilitate the multi-angle reconstruction of volume planes and thus intuitively and accurately demonstrate the spatial relationship of fetal cardiac great vessels. This effectively compensates for the limitations of 2D ultrasound sectional imaging and has substantial utility in the prenatal precise diagnosis of complex and rare fetal cardiac malformations(6-8).

This report describes a case of rare fetal RAA-BDA-ILSA, which was definitively diagnosed with STIC-HD live flow technology and summarizes the diagnostic advantages of this technique for such fetal vascular malformations.

Case presentation

A 27-year-old woman with her second pregnancy (G2P1) was referred to West China Second University Hospital for targeted fetal echocardiography at 24 weeks and 3 days of gestation after a fetal cardiac abnormality was detected on ultrasound at a local hospital. She had no family history of congenital heart disease or genetic syndromes; non-invasive DNA testing showed no abnormalities; and amniocentesis was not performed. Fetal echocardiography was performed with a Voluson E10 ultrasound system (GE HealthCare, Chicago, IL, USA) equipped with a volumetric convex transducer (2–5 MHz). Echocardiographic findings were follows: (I) the three-vessel and tracheal view (Figure 1A,1B) demonstrated the AA on the right side of the trachea and the RDA connecting the MPA and the aorta; (II) the three-vessel view (Figure 1C) further demonstrated the MPA giving rise to the LPA and right pulmonary artery (RPA). Slight tilting of the probe revealed an arterial vessel via the LDA arising from the LPA, which was coursing toward the fetal left upper limb (Figure 1D); (III) serial coronal sections of the AA and descending aorta (Figure 1E,1F) revealed that the AA was giving rise to only three brachiocephalic vessels: the LCCA, RCCA, and RSA. Figure 1G is a schematic diagram of RAA-BDA-ILSA (viewed from the ventral to dorsal aspect). STIC-HD live flow imaging was employed for the acquisition of volumetric data of fetal cardiac vessels. Following postprocessing and three-dimensional (3D) reconstruction of the volumetric data, the LCCA, RCCA, and RSA were clearly indicated to be arising sequentially from the AA in an anteroposterior manner. The LSA originated from the LPA via the LDA (Figure 1H,1I).

Figure 1.

Schematic diagram of fetal right aortic arch complicated with bilateral ductus arteriosus and isolated left subclavian artery (RAA-BDA-ILSA) at 24+3 weeks’ gestation, evaluated by 2D echocardiography, color Doppler, and STIC combined with HD live flow (STIC-HD live flow). (A,B) Three-vessel and tracheal view. The AA is located on the right side of the trachea, and the DA is also positioned on the right side of the trachea, connecting the MPA to the aorta. (C) Three-vessel view showing the MPA giving off the left and right pulmonary arteries. (D) With slight probe angulation, a vessel, namely the LSA, could be observed arising from the LPA via the LDA and coursing toward the fetal left upper extremity. (E,F) Serial coronal views of the AA and descending aorta, revealing the AA giving rise to three brachiocephalic vessels: the LCCA, RCCA, and RSA. (G) Ventral-to-dorsal anatomical schematic demonstrating the topographic distribution of fetal mediastinal vessels. (H,I) STIC volume acquisition combined with HD live rendering, which intuitively and three-dimensionally displayed the sequential origin of the LCCA, RCCA, and RSA from the AA in an anteroposterior order; the LSA appeared to originate from the LPA via the LDA. 2D, two-dimensional; AA, aortic arch; BDA, bilateral ductus arteriosus; DA, ductus arteriosus; DAO, descending aorta; HD, high-definition; ILSA, isolated left subclavian artery; L, left; LCCA, left common carotid artery; LDA, left ductus arteriosus; LPA, left pulmonary artery; LSA, left subclavian artery; MPA, main pulmonary artery; R, right; RAA, right aortic arch; RCCA, right common carotid artery; RDA, right ductus arteriosus; RPA, right pulmonary artery; RSA, right subclavian artery; STIC, spatiotemporal image correlation; SVC, superior vena cava; T, trachea.

At 40 weeks of gestation, the patient vaginally delivered a female infant. Neonatal echocardiography (Figure 2) performed on postnatal day 3 confirmed the prenatal diagnosis. Figure 2A shows the LDA connecting the pulmonary artery and the LSA. Figure 2B displays the biphasic bidirectional blood flow spectrum of the LDA.

Figure 2.

Neonatal echocardiography confirmed the prenatal diagnosis. (A) The LDA connecting the pulmonary artery and the LSA. (B) A biphasic bidirectional flow spectrum within the LDA. LDA, left ductus arteriosus; LSA, left subclavian artery.

On telephone follow-up, whole-exome sequencing (WES) at 7 months of age confirmed Menke-Hennekam syndrome type I (MKHK1). The child is currently 5 years old. Neurological and developmental assessment by a pediatric specialist revealed significant language delay, with expressive language ability estimated to be equivalent to that of a 2-year-old child. Growth parameters indicate short stature compared with age-matched peers. However, no significant abnormalities were reported in the digestive or motor systems. The infant previously presented with poor physical condition, inability to walk, and protein allergy; these symptoms have partially improved with age and appropriate management. Unfortunately, a detailed genetic report, including the specific pathogenic variant and its classification, could not be retrieved, as WES was performed approximately 5 years ago at an external commercial genetic testing company. All procedures described in this study were performed in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patient for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Fetal RAA-BDA-ILSA is a rare combined developmental anomaly of the AA branching and ductal system, embryologically resulting from regression of the left fourth AA and persistence of bilateral sixth AAs. The term isolated indicates that a given arch vessel arises exclusively from the pulmonary artery via the ductus arteriosus, with no connection to the aorta. This concept was first proposed by Stewart in 1964 (1) and restated by Li et al. in 2019(2). Fetal RAA-BDA-ILSA has an estimated prenatal incidence of 1/20,000–1/50,000 and accounts for fewer than 5% of all right-sided AA variants(2). RAA-BDA-ILSA is a condition predominantly documented in neonates (9-13). A prenatal diagnosis of RAA-BDA-ILSA has been documented in only a limited number of cases (3-6,13-16). Wen et al. first described the prenatal sonographic manifestations of RAA-BDA-ILSA at 24 weeks’ gestation, with consistent imaging findings to those of our case; this highlights the substantial diagnostic difficulty of this uncommon vascular anomaly (4). Li et al. further stressed the necessity of systematic assessment of the three-vessel view and AA branches for identifying isolated subclavian artery malformations including ILSA (5). Notably, Bellsham-Revell et al. demonstrated that BDA complicated with ILSA may coexist with complex intracardiac anomalies, including ventriculo-arterial discordance and ventricular septal defect (3). In a recent study, Yang et al. proposed that aberrant pulmonary artery branch counts on prenatal ultrasound can act as a preliminary clue for the early detection of isolated subclavian artery malformations (13). Compared with these previous reports, our case is novel in three aspects: first, we provide detailed STIC-HD live flow volumetric imaging documentation, which has not been systematically presented in previous prenatal reports; second, we describe the first known association of RAA-BDA-ILSA with genetically confirmed MKHK1; and third, we provide postnatal imaging and clinical follow-up confirmation of the prenatal findings.

The prognosis of fetal RAA-BDA-ILSA varies. Some cases are associated with 22q11.2 microdeletion, tracheobronchial dysplasia, and vascular ring malformation, while simple isolated cases are generally asymptomatic and have an excellent long-term prognosis. Hence, accurate prenatal diagnosis of fetal RAA-BDA-ILSA can facilitate standardized and refined prenatal genetic counseling.

From a genetic perspective, this case underscores the critical importance of advanced postnatal genetic testing in fetuses presenting with the RAA-BDA-ILSA association. Although the patient underwent noninvasive prenatal testing (NIPT) during pregnancy, which yielded normal results, WES of the infant performed at 7 months of age ultimately confirmed a diagnosis of MKHK1. This clinical scenario highlights a well-recognized limitation of standard NIPT: while NIPT is highly sensitive in detecting common chromosomal aneuploidies (e.g., trisomies 21, 18, and 13), it does not detect rare monogenic disorders such as Menke-Hennekam syndrome, which are unrelated to these chromosomal abnormalities. Therefore, when complex vascular malformations such as RAA-BDA-ILSA are identified prenatally, clinicians should counsel parents regarding the potential benefits of comprehensive postnatal genetic evaluation, including WES, to facilitate accurate syndromic diagnosis, guide clinical management, and inform long-term prognostication.

MKHK1 (Online Mendelian Inheritance in Man no. 618332) is a rare autosomal dominant disorder caused by pathogenic variants in exon 30 or 31 of the CREBBP gene (or less commonly, the EP300 gene), which encodes the CREB-binding protein (17,18). These specific mutations are distinct from those causing classical Rubinstein-Taybi syndrome, although both disorders involve the same genes. The major clinical manifestations of MKHK1 include intellectual disability, short stature, microcephaly, characteristic facial dysmorphisms, feeding difficulties, and variable congenital anomalies (17). Cardiovascular involvement has been documented in MKHK1, including ventricular septal defects, atrial septal defects, and patent ductus arteriosus (18,19). However, to the best of our knowledge, the specific association of RAA-BDA-ILSA with Menke-Hennekam syndrome has not been previously reported. This case therefore expands the known phenotypic spectrum of cardiovascular anomalies associated with MKHK1 and suggests that complex AA anomalies may be part of the clinical presentation of this rare syndrome.

In this case, conventional 2D echocardiography and color Doppler successfully identified the key components of the malformation: the right-sided AA, the RAA connecting the MPA to the aorta, the LDA arising from the LPA, and the three brachiocephalic branches originating from the AA. However, demonstrating the continuity and spatial interrelationships of these vascular structures required integration of findings from multiple 2D planes, which may be challenging for less experienced examiners. STIC-HD live flow provided added value by simultaneously rendering the 3D spatial relationships of the AA, its branches, and the BDA in a single volumetric image (Figure 1H,1I). This enabled the following: (I) intuitive visualization of the entire vascular complex for surgical or interventional planning; (II) clear demonstration that the LSA was indeed isolated—arising exclusively from the LPA via the LDA with no connection to the aorta; and (III) facilitation of multidisciplinary communication by providing a comprehensible 3D representation of the complex anatomy. Therefore, rather than replacing 2D imaging, STIC-HD live flow served as a complementary tool that enhanced diagnostic confidence and anatomical documentation in this complex case.

We acknowledge as a limitation in this case that the detailed WES report—including the specific pathogenic variant in CREBBP or EP300 and its classification according to the American College of Medical Genetics and Genomics guidelines—could not be retrieved for this case, as the testing was performed several years previously at an external facility.

Conclusions

In conclusion, RAA-BDA-ILSA is an uncommon developmental variant of the fetal AA. Second-trimester 2D multiplanar ultrasound combined with STIC-HD live flow 3D flow imaging can clearly depict the characteristic anatomical features of this anomaly and enable accurate prenatal classification, thereby providing robust imaging evidence for prenatal genetic counseling, perinatal clinical management, and long-term prognostic assessment.

Supplementary

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Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patient for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.