Figure.

The vast majority of the known causes of congenital heart defects (CHD) are de novo or inherited genetic abnormalities. A monogenic basis can be identified in one-third of all cases. The Baltimore-Washington Infant Study and Metropolitan Atlanta Congenital Defects Program yielded similar estimates for the fraction attributable to chromosomal syndromes.^4,5 De novo copy number variants (CNVs) include both the well-known, such as the 22q11.2 deletion, and more recently discovered ones.⁶ The fraction attributable to de novo mutations that affect protein-coding sequence were recently reported in 3 large, whole-exome sequencing studies of trios.^7–9 The burden of inherited loss-of-function mutations of known CHD genes was estimated in one of these studies.⁹ Inherited CNVs and other forms of genetic mutation cause monogenic CHD, but their attributable fractions have not been quantified in large studies similar to the ones cited above. An oligogenic basis may explain a large fraction of the currently unknown causes.