Hsp90 and complex birth defects: A plausible mechanism for the interaction of genes and environment

•Exposure to heat and oxidative stress is a trigger of a variety of birth defects.•Hsp90 chaperones proteins involved in developmental pathways, genomic stability and can mask sequence variation.•Exposure to stress causes Hsp90 to abandon its normal physiological functions to assist with general protein misfolding responses.•This results in simultaneous reduction of signaling pathways and unmasking of potentially deleterious variants.•How these mechanisms contribute to birth defects with complex etiologies remains relatively unexplored.