Congenital heart defects in CHARGE: The molecular role of CHD7 and effects on cardiac phenotype and clinical outcomes

Am J Med Genet C Semin Med Genet. 2020 Mar;184(1):81-89. doi: 10.1002/ajmg.c.31761. Epub 2019 Dec 13.

Abstract

CHARGE syndrome is characterized by a pattern of congenital anomalies (Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth, Genital abnormalities, and Ear abnormalities). De novo mutations of chromodomain helicase DNA binding protein 7 (CHD7) are the primary cause of CHARGE syndrome. The clinical phenotype is highly variable including a wide spectrum of congenital heart defects. Here, we review the range of congenital heart defects and the molecular effects of CHD7 on cardiovascular development that lead to an over-representation of atrioventricular septal, conotruncal, and aortic arch defects in CHARGE syndrome. Further, we review the overlap of cardiovascular and noncardiovascular comorbidities present in CHARGE and their impact on the peri-operative morbidity and mortality in individuals with CHARGE syndrome.

Keywords: CHARGE; CHD7; congenital heart defects.

Publication types

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

MeSH terms

  • CHARGE Syndrome / complications
  • CHARGE Syndrome / genetics*
  • CHARGE Syndrome / pathology
  • DNA Helicases / genetics*
  • DNA-Binding Proteins / genetics*
  • Genitalia / abnormalities
  • Heart Defects, Congenital / complications
  • Heart Defects, Congenital / genetics*
  • Heart Defects, Congenital / pathology
  • Humans
  • Mutation / genetics

Substances

  • DNA-Binding Proteins
  • DNA Helicases
  • CHD7 protein, human