The impact of hypocalcemia on full scale IQ in patients with 22q11.2 deletion syndrome

Am J Med Genet A. 2018 Oct;176(10):2167-2171. doi: 10.1002/ajmg.a.40535.

Abstract

Hypocalcemia has been reported in ~50% of patients 22q11.2DS and calcium regulation is known to play a role in neuronal development and synaptic plasticity. Because calcium ions play a role in neuronal function and development, we hypothesized that hypocalcemia would be associated with adverse effects on full scale IQ index (FSIQ) in patients with 22q11.2DS. A retrospective chart review cataloguing the presence or absence of hypocalcemia in 1073 subjects with a laboratory confirmed chromosome 22q11.2 deletion evaluated at the Children's Hospital of Philadelphia was conducted. 852/1073 patients had an endocrinology evaluation with laboratory confirmed calcium levels. 466/852 (54.7%) had a diagnosis of hypocalcemia. 265/1073 subjects ranging from 0 to 51 years of age had both calcium levels measured and a neuropsychological evaluation yielding a FSIQ. The mean FSIQ for 146/265 patients with hypocalcemia was 77.09 (SD = 13.56) and the mean FSIQ for 119/265 patients with normocalcemia was 77.27 (SD = 14.25). The distribution of patients with intellectual disability (ID) (FSIQ<69), borderline IQ (FSIQ 70-79), and average IQ (FSIQ>80) between the hypocalcemic and normocalcemic groups was not statistically significant (χ2 = 0.2676, p = 0.8748). Neonatal hypocalcemic seizures were not found to be associated with ID. We found no difference in FSIQ between the hypocalcemic and non-hypocalcemic patients with 22q11.2DS. As our findings differ from a previous report in adult subjects, we speculate that this may reflect a potential benefit from early treatment of hypocalcemia and may support early 22q11.2 deletion detection in order to offer prompt diagnosis and subsequent treatment of hypocalcemia.

Keywords: 22q11.2 deletion syndrome; DiGeorge syndrome; cognitive; endocrine; hypocalcemia; intellectual disability.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Calcium / blood
  • Child
  • Child, Preschool
  • Chromosome Deletion
  • Chromosomes, Human, Pair 22 / genetics*
  • DiGeorge Syndrome / etiology*
  • DiGeorge Syndrome / psychology
  • Female
  • Humans
  • Hypocalcemia / etiology
  • Hypocalcemia / psychology*
  • Infant
  • Infant, Newborn
  • Intellectual Disability / genetics
  • Intelligence Tests*
  • Male
  • Middle Aged
  • Wechsler Scales

Substances

  • Calcium