Saethre-Chotzen syndrome (acrocephalo-syndactyly type III, ACS III) is an 
autosomal dominant craniosynostosis with brachydactyly, soft tissue syndactyly 
and facial dysmorphism including ptosis, facial asymmetry and prominent ear 
crura. ACS III has been mapped to chromosome 7p21-22. Of interest, TWIST, the 
human counterpart of the murine Twist gene, has been localized on chromosome 
7p21 as well. The Twist gene product is a transcription factor containing a 
basic helix-loop-helix (b-HLH) domain, required in head mesenchyme for cranial 
neural tube morphogenesis in mice. The co-localisation of ACS III and TWIST 
prompted us to screen ACS III patients for TWIST gene mutations especially as 
mice heterozygous for Twist null mutations displayed skull defects and 
duplication of hind leg digits. Here, we report 21-bp insertions and nonsense 
mutations of the TWIST gene (S127X, E130X) in seven ACS III probands and 
describe impairment of head mesenchyme induction by TWIST as a novel 
pathophysiological mechanism in human craniosynostoses.