HAND2 and Saethre-Chotzen syndrome: Systemic loss of Twist1 results in mid-gestation lethality that is accompanied by hypoplastic limbs (Chen and Behringer, 1995), while Twist1 heterozygous mice exhibit a partially penetrant preaxial polydactyly modeling Saethre-Chotzen syndrome (SCS) that can be rescued by a gene dosage reduction in Hand2 (a Twist1 antagonist; Firulli et al., 2005).