Association of Hypocalcemia with Congenital Heart Disease in 22q11.2 Deletion Syndrome

Presentation Number: SUN 333
Date of Presentation: April 2nd, 2017

Arpana Rayannavar*1, Lorraine Katz2, Terrence Crowley3, Kathryn Grand3, Megan Lessig3, Elaine Zackai3, Beverly Emanuel3, Katherine Lord3, Vaneeta Bamba3 and Donna McDonald-McGinn3
1Children's Hospital of Philadelphia, Philadelphia, PA, 2Children's Hospital of Philadelphia, PA, PA, 3The Children's Hospital of Philadelphia, Philadelphia, PA


Introduction: Hypocalcemia is one of the cardinal features of 22q11.2 deletion syndrome (22q11.2 DS). Hypocalcemia and other features of 22q11.2 deletion syndrome including congenital heart disease (CHD), immunodeficiency, and palatal anomalies, are primarily ascribed to problems with morphogenesis and function of the pharyngeal arch system derivatives including craniofacial structures, the thymus and parathyroid glands, the aortic arch, and the cardiac outflow tract. We previously reported hypocalcemia and CHD (particularly conotruncal anomalies) in 50% and 74% of patients with 22q11.2DS respectively. In light of the aforementioned embryology, we hypothesized that hypocalcemia would be identified more frequently in those patients with 22q11.2DS and CHD. Methods: We conducted a retrospective IRB approved chart review on 1300 subjects with 22q11.2DS evaluated via the 22q and You Center at the Children’s Hospital of Philadelphia. 22q11.2 deletions were confirmed clinically using FISH, CGH, SNP microarray, or MLPA. Fisher's exact test measured differences between the groups. Results: 852 patients had both formal cardiac evaluations and calcium levels available for review. Of these, 466 (54.6%) had a diagnosis of hypocalcemia and 550 (64.5%) had CHD. Of those with CHD, 62% had hypocalcemia, while only 38% without CHD had hypocalcemia. Thus, we established the frequency of hypocalcemia to be greater in patients with 22q11.2DS and CHD as compared to those sans CHD (p,0.001). We also analyzed age of onset of hypocalcemia in these two groups and found 69% of the group with CHD and hypocalcemia had neonatal/infantile hypocalcemia vs. 14% in the non-CHD and hypocalcemia group. Conclusion: In our large cohort of patients with 22q11.2DS, hypocalcemia was more frequently associated with CHD and was more likely to be diagnosed during infancy. This important finding may reflect an embryological association, ascertainment bias in identifying neonates in association with CHD, a resultant finding in association with a physiologic stressor (CHD), or a combination of these factors. Nonetheless, early diagnosis of 22q11.2DS, in particular as a cause of CHD, is vital in identification and early treatment of hypocalcemia.


Nothing to Disclose: AR, LK, TC, KG, ML, EZ, BE, KL, VB, DM