Authors: Sonya V. Gupta, AM, MS1 - Stanford University AND Kaitlin M. Flannery, MD, MPH - Stanford University
A 5-year-old, 15kg male with a history of Tetralogy of Fallot, pulmonary atresia and major aortopulmonary collaterals (MAPCAs) who has undergone unifocalization and complete intracardiac repair with RV-PA conduit, presents for a conduit exchange. Additional past medical history includes tracheobronchomalacia, frequent respiratory infections, and hypocalcemia requiring oral calcium supplementation. Which of the following syndromes does this patient MOST likely have?
EXPLANATION
The patient’s clinical presentation is most consistent with DiGeorge syndrome, a multisystem disorder associated with defective development of the pharyngeal pouch system and includes congenital heart disease, especially conotruncal defects including Tetralogy of Fallot, craniofacial anomalies, airway anomalies, and disorders of the endocrine, immune, and hematologic systems. It is most often caused by deletion of chromosome 22q11 (del22q11), though some patients may present with the phenotype without said mutation. While it can be inherited in an autosomal dominant pattern, most cases result from de novo mutations.1
DiGeorge syndrome is the second most common genetic syndrome resulting in congenital heart disease, following Down syndrome. The incidence is 1 in 4000 live births with 70% of patients having CHD. Most data regarding anesthetic and cardiac surgical outcomes are limited to case series and case reports. A larger single-center retrospective study, from the Mayo Clinic, published in 2012, allows examination of outcomes.2 The study included 62 unique patients undergoing 136 cardiac surgical procedures from 1976-2012. Despite craniofacial and airway anomalies, 95% of patients were intubated on the first attempt. The 3 patients who were not intubated on the first attempt, were easy to mask ventilate, and were intubated using direct laryngoscopy on attempt 2 or 3. The craniofacial and airway anomalies played a larger role postoperatively as 12% of patients required reintubation and 5% require tracheostomy. Postoperative infections occurred in 22% of cases including 6 sternal wound infections. There were no in-hospital deaths or 30-day mortality. This study did not include a control group. Therefore, it is unclear if the rates of reintubation, tracheostomy, or infection are higher in patients with DiGeorge syndrome.2
Patients with DiGeorge syndrome may have complex CHD not amenable for corrective surgery and require heart transplantation. Management of immunosuppression may be impacted by the underlying immune deficiencies. A retrospective study published in 2019, utilizing data from all pediatric heart transplants in the United States since 1986, found 17 heart transplants performed in patients with DiGeorge syndrome. Of these patients, 47% underwent transplant as an infant. Pretransplant characteristics were not significantly different from patients without a genetic syndrome. Median survival after transplant was 5.4 years in patients with DiGeorge syndrome versus >15 years in patients without DiGeorge syndrome. However, when patients were matched by age and gender, the difference in post-transplant survival did not exist. There was no significant difference in hospitalization for infection or rejection in patients with or without DiGeorge syndrome. Based on these results, the authors of this study advocate that DiGeorge syndrome should not be an absolute contraindication to heart transplantation.3
Anesthetic considerations for patients with DiGeorge syndrome involve management of the underlying cardiac lesions as well as extra-cardiac manifestations. Airway anomalies and velopharyngeal dysfunction with resulting risk of aspiration must be carefully considered. These patients are also prone to hypocalcemia from parathyroid hypoplasia and often require calcium supplementation in the perioperative period. Immune impairment from thymic hypoplasia and T-cell dysfunction makes these children at risk of infections as well as transfusion-associated graft-versus-host disease (TA-GVHD) and they should receive irradiated blood products until confirmation of normal immune function.4
The patient described in the vignette above has DiGeorge syndrome, based on the presence of conotruncal and airway anomalies, immune dysfunction and hypocalcemia. Down syndrome also presents with characteristic cardiac and craniofacial anomalies, thyroid dysfunction but without hypocalcemia. Goldenhar syndrome patients typically show asymmetrical midface anomalies without endocrine or cardiac manifestations.
REFERENCES
1. Bassett AS, McDonald-McGinn DM, Devriendt K, et al. Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr. 2011;159(2):332-339.e1. doi:10.1016/j.jpeds.2011.02.039
2. Yeng Yeoh T, Scavonetto F, Hamlin RJ, Burkhart HM, Sprung J, Weingarten TN. Perioperative Management of Patients With DiGeorge Syndrome Undergoing Cardiac Surgery. J Cardiothorac Vasc Anesth. 2014;28(4):983-989. doi:10.1053/j.jvca.2013.10.025
3. Woolman P, Bearl DW, Soslow JH. Characteristics and outcomes of heart transplantation in DiGeorge syndrome. Pediatr Cardiol. 2019 Feb 7;40(4):768-75. doi: 10.1007/s00246-019-02063-w
4. McDonald-McGinn DM, Hain HS, Emanuel BS, Zackai EH. 22Q11.2 deletion syndrome. GeneReviews® - NCBI Bookshelf. Published May 9, 2024. https://www.ncbi.nlm.nih.gov/books/NBK1523/
