Neonatal hypocalcemia, neonatal seizures, and intellectual disability in 22q11.2 deletion syndrome

Genet Med. 2014 Jan;16(1):40-4. doi: 10.1038/gim.2013.71. Epub 2013 Jun 13.


Purpose: Hypocalcemia is a common endocrinological condition in 22q11.2 deletion syndrome. Neonatal hypocalcemia may affect neurodevelopment. We hypothesized that neonatal hypocalcemia would be associated with rare, more severe forms of intellectual disability in 22q11.2 deletion syndrome.

Methods: We used a logistic regression model to investigate potential predictors of intellectual disability severity, including neonatal hypocalcemia, neonatal seizures, and complex congenital heart disease, e.g., interrupted aortic arch, in 149 adults with 22q11.2 deletion syndrome. Ten subjects had moderate-to-severe intellectual disability.

Results: The model was highly significant (P < 0.0001), showing neonatal seizures (P = 0.0018) and neonatal hypocalcemia (P = 0.047) to be significant predictors of a more severe level of intellectual disability. Neonatal seizures were significantly associated with neonatal hypocalcemia in the entire sample (P < 0.0001), regardless of intellectual level. There was no evidence for the association of moderate-to-severe intellectual disability with other factors such as major structural brain malformations in this sample.

Conclusion: The results suggest that neonatal seizures may increase the risk for more severe intellectual deficits in 22q11.2 deletion syndrome, likely mediated by neonatal hypocalcemia. Neonatal hypocalcemia often remains unrecognized until the postseizure period, when damage to neurons may already have occurred. These findings support the importance of early recognition and treatment of neonatal hypocalcemia and potentially neonatal screening for 22q11.2 deletions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DiGeorge Syndrome / diagnosis
  • DiGeorge Syndrome / physiopathology*
  • Female
  • Humans
  • Hypocalcemia / physiopathology*
  • Infant, Newborn
  • Intellectual Disability / physiopathology*
  • Logistic Models
  • Male
  • Neonatal Screening
  • Risk Factors
  • Seizures / physiopathology*
  • Young Adult