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In this issue of Cell, Sparrow et al. propose a new mechanism for sporadically occurring congenital scoliosis in which Notch signaling and hypoxia converge in the embryo on somite patterning via the segmentation clock. This interaction between hypoxia and a predisposed genetic background might underlie other birth defects with incomplete penetrance., (Copyright © 2012 Elsevier Inc. All rights reserved.)