Persistent fifth aortic arch complicated by Williams-Beuren syndrome: a case description

Introduction

Identifying congenital aortic arch variations and abnormalities is crucial, as they may form vascular rings or be linked to congenital heart disease. These variations and abnormalities often lead to hemodynamic disturbances and require surgical intervention (1). Persistent fifth aortic arch (PFAA) is a rare congenital vascular malformation, characterized by an additional arched vessel below the anatomy aorta arch (AAA), originating from the ascending aorta and terminating at the descending aorta or pulmonary artery; it develops when the left fifth branchial arch fails to degenerate, and the left fourth branchial arch forms an AAA (2). Most PFAA demonstrates vertical-parallel alignment with AAA, characterized by dual vascular channels bridging the ascending and descending aorta without intrinsic stenosis or bifurcation defects of the AAA (3). Researchers refers to PFAA as “the great pretender” since most PFAAs share similarities with the AAAs in terms of morphology, function, and hemodynamics, and patients often remain asymptomatic or exhibit only heart murmurs (4,5). In this article, we report an extremely rare but intriguing case of PFAA combined with Williams-Beuren syndrome (WBS) that eventually led to cerebral infarction, and we provide both pre-and postoperative images of the heart and vessels.

Case presentation

A 10-year-old male presented to Shenzhen Children’s Hospital with a 13-hour onset of hemiplegia and headache. The patient had a medical history of WBS and an 11-month history of intermittent fever. Upon physical examination, the following observations were noted: body temperature (BT): 38.1 ℃, blood pressure: 206/108 mmHg, heart rate: 108/min, and respiratory rate: 29/min. The patient’s bilateral muscle strength was notably decreased, particularly in the right limb. Knee and ankle reflexes were absent on the right, which also had a positive Babinski sign, and weakened on the left. Cardiac auscultation revealed a grade 4/6 systolic murmur in the second intercostal space at the left border. Routine blood tests showed an elevated white blood cell (WBC) count of 15.01×10⁹/L (neutrophils: 92.5%), and C-reactive protein levels of 34.7 mg/L.

Head magnetic resonance imaging showed swelling of the left parietotemporal gyrus and blurring of gray-white matter demarcation. The lesion showed hyperintensity on T2-weighted images and fluid-attenuated inversion-recovery images, and diffusion-weighted images indicated diffusion restriction in this area, suggesting cerebral infarction (Figure 1A-1D). Echocardiography revealed aortic vegetation with calcification, which, given the elevated BT and WBC count, prompted an immediate suspicion of infective endocarditis that was further supported by a positive serum anti-streptolysin O test. Chest contrast-enhanced computed tomography (CT) revealed thickening of the aortic and left ventricular walls (particularly of the ventricular septum), along with stenosis of the supra-valvular aorta and pulmonary arteries (Figure 2A,2B). These findings aligned with the cardiovascular manifestations of WBS. A double-lumen aortic arch was observed, connecting the ascending and descending aorta. The two arches were arranged up and down (with inner diameters of 8.6 and 7.6 mm, respectively), and all supra-aortic arteries originated from the upper arch (the left common carotid artery and left subclavian artery shared a common trunk). No vascular ring or stenosis was detected. All these signs suggested PFAA. Further, irregular vegetation with spotted calcification was observed in the ascending aortic lumen, and it was attached to the “dividing dike” (Figure 3A-3C), and was consistent with a diagnosis of vegetation secondary to infective endocarditis. Patent ductus arteriosus (PDA) was also observed in the image (Figure 4).

Figure 1 Head magnetic resonance imaging. (A) T2-weighted image; (B) fluid-attenuated inversion-recovery image; (C) diffusion-weighted image (b=800 s/mm²); (D) apparent diffusion coefficient image.

Figure 2 Chest contrast-enhanced computed tomography-multi-planar reformation. (A) Thickening of the aortic wall, and stenosis of the supra-valvular aorta (“→”), and left ventricular wall (“▲”). (B) Stenosis of the pulmonary arteries (“→”).

Figure 3 Chest contrast-enhanced computed tomography-maximum intensity projection, and volume rendering. (A) A double-lumen aortic arch: the AAA was observed in the upper arch, while PFAA was observed in the lower arch. Calcified vegetation that attached to the “dividing dike” (“→”) was also observed in the image. (B) Posterior view of volume rendering; pulmonary vessels and the heart were processed transparently. (C) Irregular calcified vegetation was observed in the ascending aorta (colored in green). Both arches connect the ascending and descending aorta. The left common carotid artery and left subclavian artery shared a common trunk (“▲”). Stenosis of the supra-valvular aorta (“★”). AAA, anatomic aortic arch; BCA, brachiocephalic artery; LCCA, left common carotid artery; LSA, left subclavian artery; PFAA, persistent fifth aortic arch.

Figure 4 Chest contrast-enhanced computed tomography-multi-planar reformation: patent ductus arteriosus was also observed in the image (“→”). DA, descending aorta; PA, pulmonary artery.

Based on the above results, the following clinical diagnosis was made: (I) WBS; (II) congenital heart disease: PFAA (Weinberg type A) with PDA; (III) infective endocarditis with calcified vegetation; and (IV) acute cerebral infarction of the left parietotemporal lobe.

The patient underwent angioplasty to address the additional lumen and enlarged stenotic vessels, along with antibiotic therapy and other treatments. The postoperative pathological results showed that the vegetation consisted of necrotic tissue with calcification, intimal fibroplasia of the aortic wall, fibromuscular hyperplasia of the media with a large number of neutrophils, and lymphocytes and other inflammatory cells. At the three-year follow-up, the patient still suffered from right limb dysfunction as the sequel of infarction but had recovered well in cardiovascular terms (Figure 5).

Figure 5 Chest contrast-enhanced computed tomography-multi-planar reformation. (A) Preoperative image. (B) Postoperative image.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with Declaration of Helsinki and its subsequent amendments. Written informed consent was provided by the patient’s legal guardian 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

PFAA is an extremely rare congenital vascular malformation (1). Since it was first reported by Van Praagh et al. (6) in 1969, less than 200 relevant cases have been reported, most of which were based on autopsy studies. There are no precise epidemiological data on the incidence of PFAA. Gerlis et al. (2) reviewed 2,000 cases of congenital cardiovascular disease, of which, only six were identified as PFAA (0.3% of the congenital cardiovascular disease cases). While Yu et al. (7) reviewed 15,663 cases of congenital cardiovascular disease diagnosed by the Radiology Department of Fuwai Hospital of the Chinese Academy of Medical Sciences, and identified only eight cases of PFAA (0.5% of congenital cardiovascular disease).

The etiology of PFAA remains controversial. Most researchers, including Bamforth et al. (3,7-9) believe that six pairs of pharyngeal arches develop during human embryonic development between the abdominal and the dorsal aorta (similar to fish gills), and PFAA occurs when the fifth pharyngeal arch fails to degenerate. However, Graham et al. (10) challenged this notion using a reconstruction analysis and homology studies with human and mouse embryos. Their results disproved the existence of the so-called fifth pharyngeal arch during embryonic development, and they conjectured that PFAA may be caused by collateral circulation or the development of the aortic sac.

In relation to the diagnostic criteria for PFFA, Gupta et al. (11) noted that: (I) PFAA must originate from the ascending aorta proximal to the bifurcation of the brachiocephalic artery; and (II) PFAA must terminate directly at the descending aorta, or the pulmonary artery, and then subsequently extend via PDA (the sixth arches) to connect to the descending aorta. There is no recommended classification of PFAA, but different approaches include the Freedom, Oppido, and Weinberg classifications (5,12-14).

This study adopted the Weinberg classification, which categorizes the condition into the following three types: (I) type A: a double-lumen aortic arch with or without arch hypoplasia or coarctation; (II) type B: atresia or interruption of the fourth aortic arch with a PFAA; and (III) type C: a systemic-to-pulmonary arterial connection with or without pulmonary or systemic arterial obstruction. The discussed case aligns with Weinberg type A; it shares similarities with the AAA in terms of morphology, function, and hemodynamics. However, in this case, the patient presented with persistent symptoms and developed a rare pediatric condition (i.e., cerebral infarction). These manifestations may be closely related to the joint affection of PFAA and WBS.

WBS is a genetic disorder caused by a microdeletion in the elastin gene located on the long arm of chromosome 7, which leads to the reduction of elastic fibers and the overgrowth of smooth muscle in the media layer of elastic vessels, creating an overall effect of vascular stenosis (most commonly seen at the supra-valvular aorta) and a reduction in vascular compliance (15,16), which is consistent with the pathological findings in our case. Hemodynamics changed due to the stenosis of the supra-valvular aorta. Rapid flow from the left ventricle continually impacted the “dividing dike”, which was already structurally incapable, damaging the structure and creating turbulence. Streptococcus colonization of the injured aortic wall led to vegetation formation. When branches of the left middle cerebral artery became partially detached and blocked, ischemic cerebral infarction developed. During this process, symptoms such as heart murmurs, persistent fever, headache, and hemiplegia emerged.

Both PFAA and WBS contributed to the complexed clinical presentation of this patient. PFAA has been shown to frequently co-occur with other congenital cardiovascular anomalies such as atrial septal defects, ventricular septal defects, and oculoauriculovertebral spectrum as reported in several case reports (2,14,17). This may be due to the mutation in chromosome 22q11.2, which has been widely discussed as having the potential to cause congenital cardiovascular diseases, especially aortic arch malformation (18). However, to date, no reports have established a definitive correlation between PFAA and WBS, which remains to be verified. In this case, the patient’s history of WBS, along with the vascular anomalies associated with PFAA, created a favorable environment for bacterial colonization, making the patient particularly susceptible to complications such as infective endocarditis, which could complicate congenital heart defects and exacerbate the patient’s clinical condition.

The accurate identification of PFAA is crucial for making appropriate treatment decisions. Type A PFAA with AAA features two intact arches which differs from the double-aortic arch (DAA). In the DAA, the two arches bifurcate anteriorly, encircling the trachea and esophagus, thus forming a vascular ring. The arches may or may not converge posteriorly, but they are consistently arranged in a horizontal-parallel order. Moreover, supra-aortic arteries originate from the ipsilateral aortic arch. Conversely, type A PFAA diverges vertically from the ascending aorta, forming two parallel arches in vertical-parallel order, with all supra-aortic arteries originating from the upper arch (the AAA). Type B PFAA can be differentiated by the interruption of the aortic arch (IAA). In the IAA, there is no direct connection between the ascending and descending aorta, and the bloodstream of the descending aorta comes entirely from the pulmonary artery. IAA patients often present with abnormalities, such as atrial septal or ventricular septal defects that enable systemic circulation to obtain adequate oxygenated blood required for survival. Type B PFAA features a partially or fully severed AAA and a narrowed fifth arch that directly connects the ascending and descending aorta, providing blood to the systemic circulation. The significant distinction between type C PFAA and PDA and somatopulmonary collateral circulation lies in the location of bifurcation. Gupta et al. (11,19) concluded that PFAA originates from the ascending aorta, proximal to the bifurcation of the brachiocephalic artery, while PDA and somatopulmonary collateral circulation arise from the aortic isthmus.

The early detection of PFAA is essential, and imaging findings play a critical role in its clinical management. Weinberg type A PFAA can often be monitored by regular follow-ups, while type B (with aortic stenosis) and type C (with aortic-pulmonary shunt) generally require surgical intervention due to the higher risk of hemodynamic instability and related complications. Chest contrast-enhanced CT and magnetic resonance images, aided by post-processing and reconstruction techniques such as multi-planar reformation and volume rendering reconstruction, are invaluable in detecting PFAA, and provide an objective and direct view for practitioners. PFAA requires early diagnosis and regular monitoring to detect any hemodynamic changes, as this is the only way to prevent sudden medical events, such as cerebral infarction.

Acknowledgments

None.

Footnote

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-919/coif). The authors have no conflicts of interest to declare.

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 Declaration of Helsinki and its subsequent amendments. Written informed consent was provided by the patient’s legal guardian 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.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Hanneman K, Newman B, Chan F. Congenital Variants and Anomalies of the Aortic Arch. Radiographics 2017;37:32-51. [Crossref] [PubMed]
2. Gerlis LM, Ho SY, Anderson RH, Da Costa P. Persistent 5th aortic arch--a great pretender: three new covert cases. Int J Cardiol 1989;23:239-47. [Crossref] [PubMed]
3. Subramanyan R, Sahayaraj A, Sekar P, Cherian KM. Persistent fifth aortic arch. J Thorac Cardiovasc Surg 2010;139:e117-8. [Crossref] [PubMed]
4. Lloyd DFA, Ho SY, Pushparajah K, Chakraborty S, Nasser M, Uemura H, Franklin R, Magee AG. Persistent fifth aortic arch: the "great pretender" in clinical practice. Cardiol Young 2018;28:175-81. [Crossref] [PubMed]
5. Weinberg PM. Aortic arch anomalies. J Cardiovasc Magn Reson 2006;8:633-43. [Crossref] [PubMed]
6. Van Praagh R, Van Praagh S. Persistent fifth arterial arch in man. Congenital double-lumen aortic arch. Am J Cardiol 1969;24:279-82. [Crossref] [PubMed]
7. Yu JH, Zhi AH, Li N, Wang EN, Qi XQ, Jiang SL, Dai RP, Lyu B. Anatomical features of persistent fifth aortic arch evaluated by various imaging modalities. Chin J Circ 2021;36:1020-6.
8. Bamforth SD, Chaudhry B, Bennett M, Wilson R, Mohun TJ, Van Mierop LH, Henderson DJ, Anderson RH. Clarification of the identity of the mammalian fifth pharyngeal arch artery. Clin Anat 2013;26:173-82. [Crossref] [PubMed]
9. Naimo PS, Vazquez-Alvarez Mdel C, d'Udekem Y, Jones B, Konstantinov IE. Double-Lumen Aortic Arch: Persistence of the Fifth Aortic Arch. Ann Thorac Surg 2016;101:e155-6. [Crossref] [PubMed]
10. Graham A, Hikspoors JPJM, Anderson RH, Lamers WH, Bamforth SD. A revised terminology for the pharyngeal arches and the arch arteries. J Anat 2023;243:564-9. [Crossref] [PubMed]
11. Gupta SK, Gulati GS, Anderson RH. Clarifying the anatomy of the fifth arch artery. Ann Pediatr Cardiol 2016;9:62-7. [Crossref] [PubMed]
12. Oppido G, Davies B. Subclavian artery from ascending aorta or as the first branch of the aortic arch: another variant of persistent fifth aortic arch. J Thorac Cardiovasc Surg 2006;132:730-1; author reply 731. [Crossref] [PubMed]
13. Yang H, Zhu X, Wu C, Zhao X, Ji X. Assessment of persistent fifth aortic arch by echocardiography and computed tomography angiography. Medicine (Baltimore) 2020;99:e19297. [Crossref] [PubMed]
14. Balaban İ, Bilgici MC, Baysal K. A new association of Oculoauriculovertebral spectrum and persistent fifth aortic arch -double lumen aorta: a case report. BMC Pediatr 2022;22:102. [Crossref] [PubMed]
15. Pober BR. Williams-Beuren syndrome. N Engl J Med 2010;362:239-52. [Crossref] [PubMed]
16. Pober BR, Johnson M, Urban Z. Mechanisms and treatment of cardiovascular disease in Williams-Beuren syndrome. J Clin Invest 2008;118:1606-15. [Crossref] [PubMed]
17. Liu Y, Zhang H, Ren J, Cao A, Guo J, Liu B, Bao M, Zheng C. Persistent fifth aortic arch: a single-center experience, case series. Transl Pediatr 2021;10:1566-72. [Crossref] [PubMed]
18. Yamagishi H, Garg V, Matsuoka R, Thomas T, Srivastava D. A molecular pathway revealing a genetic basis for human cardiac and craniofacial defects. Science 1999;283:1158-61. [Crossref] [PubMed]
19. Santoro G, Caianiello G, Palladino MT, Iacono C, Russo MG, Calabrò R. Aortic coarctation with persistent fifth left aortic arch. Int J Cardiol 2009;136:e33-4. [Crossref] [PubMed]