In addition to gene mutations, other potential contributing factors include rare copy number variations [29] and other chromosome abnormalities [30]. However, like most of the single-gene defects, these are rare and unlikely to contribute significantly to the incidence of AVSD. Environmental factors may also contribute, including gene x environment interactions such as genetic variants that affect folate metabolism [31] and epigenetics [32]. However, these areas are largely unexplored at this point and deserve further attention.