Association of hypocalcemia with congenital heart disease in 22q11.2 deletion syndrome

Am J Med Genet A. 2018 Oct;176(10):2099-2103. doi: 10.1002/ajmg.a.40495. Epub 2018 Oct 1.

Abstract

Hypocalcemia is one of the cardinal features of the chromosome 22q11.2 deletion syndrome (22q11.2DS), the most common cause of DiGeorge syndrome. Hypocalcemia and other features of 22q11.2DS including congenital heart disease (CHD) are primarily ascribed to problems with morphogenesis and function of the pharyngeal arch system derivatives including the parathyroid glands, the aortic arch, and the cardiac outflow tract. In light of the aforementioned embryology, we hypothesized that hypocalcemia would be identified more frequently in those patients with 22q11.2DS and CHD. We conducted a retrospective IRB approved chart review on 1,300 subjects with 22q11.2DS evaluated at the Children's Hospital of Philadelphia. χ2 test was used to evaluate the statistical significance of differences in hypocalcemia between the two groups. Eight hundred fifty-two patients had calcium levels available for review. Of these, 466 (54.69%) had a history of hypocalcemia and 550 (64.55%) had CHD. Of those with CHD, 343 (62.36%) had a history of hypocalcemia, and of those without CHD, only 123 (40.73%) had a history of hypocalcemia. Thus, the frequency of diagnosed hypocalcemia was greater in patients with 22q11.2DS and CHD as compared to those without CHD (p < .001). We also analyzed age of onset of hypocalcemia and found that 66.47% of CHD/hypocalcemia group had neonatal/infantile hypocalcemia versus 43.09% in the non-CHD/hypocalcemia group. In our large cohort of patients with 22q11.2DS, the prevalence of diagnosed hypocalcemia is elevated among patients with CHD, in whom it is more likely to be diagnosed during the neonatal/infancy period.

Keywords: congenital heart disease; hypocalcemia22q11.2 microdeletion.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Child
  • Child, Preschool
  • DiGeorge Syndrome / genetics*
  • Female
  • Heart Defects, Congenital / genetics*
  • Humans
  • Hypocalcemia / diagnosis*
  • Hypocalcemia / genetics*
  • Infant
  • Infant, Newborn
  • Male
  • Retrospective Studies
  • Young Adult