Converging signalling disruptions: a threshold for Down syndrome hearts.

Why do half of all children with Down syndrome have heart defects? Recent studies show that multiple chromosome 21 genes-most notably the chromatin regulator high-mobility group nucleosome-binding domain 1-collectively disrupt bone morphogenetic protein, Wingless/Integrated, Neurogenic locus notch homolog, and calcineurin-nuclear factor of activated T cells signalling. In this forum, we propose a convergent threshold model for these cardiac malformations.