A rare constellation: Interrupted aortic arch type C and confirmed 22q11 deletion (DiGeorge syndrome) managed with Yasui procedure in a neonate

ABSTRACT

Interrupted aortic arch (IAA) type C is a rare and complex congenital heart anomaly. DiGeorge syndrome (22q11.2 deletion) is commonly associated with conotruncal anomalies, notably IAA type B, but its association with IAA type C is exceptional. There is only a limited number of reported cases in the literature. Here, we present a case of a full-term neonate diagnosed with IAA type C and confirmed to have 22q11.2 deletion syndrome. It was managed successfully with a Yasui procedure. Our case highlights the critical importance of genetic screening for early diagnosis and the necessity of a proper multidisciplinary team approach. Prompt surgical intervention in these patients is life-saving.

INTRODUCTION

Interrupted aortic arch (IAA) is a complex congenital heart anomaly with a complete discontinuity between the ascending and descending aorta. Based on the site of the interruption, IAA is classified into three anatomical types, with type C being the rarest.[1,2]

DiGeorge syndrome is the most common microdeletion syndrome, with a prevalence of one in 5000 live births. In the 1960s, it was first described as a clinical triad of immunodeficiency, hypoparathyroidism, and congenital heart disease. It is currently recognized as a multisystem disorder.[3,4,5,6]

The association between DiGeorge syndrome and IAA type C is very rare. To date, only a few cases have been described in the literature, making it a noteworthy clinical phenomenon.[7,8,9]

CASE REPORT

A female, full-term neonate developed respiratory distress within 24 h of life. Clinical examination revealed dysmorphic facial features (micrognathia, low-set ears, a peaked nose, a small mouth and lips, no cleft lip or palate). Chest radiography showed signs of pulmonary vascular congestion. Echocardiography (ECHO) and cardiac computed tomography (CT) [Figure 1,2] revealed: IAA type C with interruption between the right and left common carotid arteries, aberrant right subclavian artery (RSCA) forming a partial vascular ring, large (9 mm) patent ductus arteriosus (PDA) forming a ductal arch, small (2.5 mm, Z-score = − 3.5) left ventricular outflow tract (LVOT) giving rise to a small (3.7 mm, Z-score = − 3.3) ascending aorta through a small bicuspid aortic valve (annulus 2.7mm, Z-score = − 5.2), large perimembranous ventricular septal defect (PMVSD), and secundum atrial septal defect (ASDII). She was started on prostaglandin E₁ and placed on mechanical ventilation. Serial blood work revealed persistent hypocalcemia (1.6–3.7 mmol/L) and mildly low serum parathyroid hormone levels (2.4–2.8 pmol/L). DiGeorge syndrome (22q11.2 deletion) was suspected; a fluorescence in situ hybridization study confirmed it [Appendix 1]. At 13 days of age, she underwent surgical repair with the Yasui procedure [Figure 3,4] in the form of aortic arch reconstruction with pulmonary homograft augmentation, and Rastelli repair using a 12 mm Contegra conduit. PDA ligation and division of the aberrant RSCA were also done. Intraoperatively, the cardiopulmonary bypass time was 121 min, and Neuroprotective measures included deep hypothermia, near-infrared spectroscopy monitoring, and maintaining optimal O₂ delivery. Postoperatively, the sternum was initially left open, and was closed on postoperative day 5. The patient required short-term inotropic support (epinephrine and norepinephrine) and inhaled nitric oxide. Shortly after chest closure, the patient showed good hemodynamic status and gradual weaning from respiratory support. She remained in the pediatric cardiac intensive care unit for 18 days, complicated by: (1) Persistent leukocytosis despite negative cultures (ruled out surgical site infection with chest CT). (2) Mild hypoparathyroidism and persistent hypocalcemia. Serial postoperative follow-up ECHO showed a patent aortic arch, unobstructed Damus–Kaye–Stansel (DKS) and right ventricle-to-pulmonary artery conduit, severe bilateral pulmonary artery origin stenosis, estimated right ventricular pressure of 65 mmHg, and good biventricular systolic function. Finally, the patient was discharged home on day 36 with aspirin, propranolol, calcium, and alfacalcidol. Family counseling was conducted. A follow-up was arranged.

Figure 1.

Three-dimensional computed tomography angiography anteroposterior projection shows: An interrupted aortic arch type C (discontinuity between right and left carotid arteries). A large ductus arteriosus (ductal arch). The left common carotid and left subclavian arteries arising from the ductal arch

Figure 2.

Three-dimensional computed tomography angiography posteroanterior projection, showing: An aberrant right subclavian artery arising from the descending aorta. The pulmonary arteries and ductus arteriosus vessels are forming an incomplete vascular ring

Figure 3.

Schematic illustration of Yasui surgical repair showing the native main pulmonary artery is proximally resected and anastomosed to the ascending aorta, creating a common systemic outflow (Damus–Kaye–Stansel [DKS]). The ventricular septal defect is tunneled to the DKS pathway. The aortic arch is reconstructed, and PDA is ligated and resected

Figure 4.

Schematic illustration of Yasui surgical repair showing: completion of the Rastelli procedure using a Contegra^® conduit connecting the right ventricle to the pulmonary artery

Literature review

The first case of IAA type C with confirmed 22q11.2 deletion was reported by Fujii et al. in Japan in 2005,[7] followed by similar isolated reports from Europe.[8,9] In most of these cases, the diagnosis was made after the development of postoperative complications or in the presence of subtle extracardiac features. Cuturilo et al. emphasized that, despite the rarity of this phenotype, clinicians should consider genetic screening in all neonates with IAA type C with accompanying facial dysmorphism and/or extracardiac anomalies.[8] In a comprehensive review, Goldmuntz outlined that a substantial proportion of patients with IAA, truncus arteriosus (TA), tetralogy of Fallot (TOF), and PMVSD have a deletion of chromosome 22q11. Deletions are more common in patients with aortic arch or vessel anomalies.[3] McDonald-McGinn et al. advocated for early genetic testing due to the variable expression of the syndrome. Early diagnosis offers multiple advantages; it can improve preparedness and outcomes, while also reducing medical and financial costs.[4] Marino and Digilio also noted that early identification has significant implications for prognosis and family planning.[5,6]

From a surgical point of view, the Yasui operation may be considered the preferred approach in neonates with LVOT obstruction (LVOTO) and adequate ventricular size. It combines a DKS anastomosis with a Rastelli-type conduit to allow for biventricular repair. Yasui operation studies by Nakano et al. and Pandey et al. have demonstrated favorable mid- to long-term outcomes, including preserved ventricular function and low mortality.[10,11]

DISCUSSION

DiGeorge syndrome is associated with a wide spectrum of manifestations. It includes hypocalcemia, immunodeficiency, palatal anomalies, facial dysmorphisms, developmental delay, and congenital heart defects, particularly conotruncal anomalies such as IAA (especially type B), TA, TOF, and ventricular septal defect.[3,4,5,6] Due to multisystem involvement, preparedness in a tertiary health facility is essential, as its management involves multiple subspecialties.

Hence, early diagnosis, guided by high clinical suspicion and confirmed with genetic testing, is crucial for improved long-term outcomes.[3,4] Although early diagnosis does not affect the cardiac treatment plan, it enables early screening, detection, and timely interventions for associated medical problems. Feeding difficulties and hypocalcemia need to be addressed in the neonatal period. Assessment of T-cell function may influence blood transfusion policies postoperatively and immunization in infancy. Family counseling, psychological support, speech, and neurodevelopmental abnormalities all require a multidisciplinary team approach. Financial cost/benefit adds to the equation.

Our case details a rare association between IAA type C and DiGeorge syndrome. While IAA type B is more commonly seen with 22q11.2 deletion, our case and the few literature reports of DiGeorge associated with IAA type C all emphasize the critical importance of maintaining a high clinical suspicion and pursuing a genetic workup even in rare subtypes.[1,2,3,7,8,9] The patient’s successful surgical repair with the Yasui operation adds to growing evidence that this technique is safe and effective. It gives excellent results with low mortality in neonates who have adequate biventricular anatomy.[10,11] Early diagnosis confirmed by genetic testing, and proper multidisciplinary care are essential for good long-term outcomes.

CONCLUSION

This case adds to the limited global literature on IAA type C with confirmed 22q11.2 deletion syndrome. It shows the importance of genetic screening for early diagnosis and confirms that genetic testing is warranted in all neonates with IAA, regardless of anatomical type. A thorough anatomic evaluation allows for appropriate surgical planning. In neonates with a narrow LVOT and adequate ventricular size, the Yasui procedure could be a valuable tool for achieving biventricular repair with good outcomes.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

APPENDIX

Appendix 1:

FISH Interpretation

Test Result: Positive:

A deletion of the Tuple1 gene was detected in all examined cells, consistent with the diagnosis of 22q11 Deletion Syndrome (DiGeorge/Velocardiofacial syndrome). Genetic counseling is indicated, which should include testing of parental blood samples to investigate the origin of this chromosomal abnormality.

Karyotype: Fish del (22)(q11.2q11.2)(TUPLE1-).

Examined metaphase cells: 20

Examined interphase cells: 200

Photographed cells: 2

Comment: The Fluorescence in situ hybridization (FISH) technique was performed using the LSI Tuple1 gene probe (Abbott) to screen for deletions of the Tuple 1 gene that have been reported in at least 90% of patients with DiGeorge/Velocardiofacial syndrome.

[CG] Chromosome Analysis Final Report

• Primary Clinical Indication: CG Chromosome Analysis Blood Postnatal

• Primary Clinical Indication: Other (CHD, to rule out DiGeorge Syndrome)

• Body site: Venous

• Test Results: Chromosome analysis revealed an apparently normal female karyotype at a low banding resolution of 525. A further blood sample may be sent for a higher chromosomal resolution study.

• Karyotype: 46, XX

• Counted Cells: 20

• Analyzed Cells: 5

• Photographed Cells: 5

• Karyogramed Cells: 5

• Banding Resolution: 525

• Staining Technique(s): GTW

Funding Statement

Nil.