Saethre-Chotzen syndrome is a relatively common craniosynostosis disorder with 
autosomal dominant inheritance. Mutations in the TWIST gene have been identified 
in patients with Saethre-Chotzen syndrome. The TWIST gene product is a 
transcription factor with DNA binding and helix-loop-helix domains. Numerous 
missense and nonsense mutations cluster in the functional domains, without any 
apparent mutational hot spot. Two novel point mutations and one novel 
polymorphism are included in this review. Large deletions including the TWIST 
gene have been identified in some patients with learning disabilities or mental 
retardation, which are not typically part of the Saethre-Chotzen syndrome. 
Comprehensive studies in patients with the clinical diagnosis of Saethre-Chotzen 
syndrome have demonstrated a TWIST gene abnormality in about 80%, up to 37% of 
which may be large deletions [Johnson et al., 1998]. The gene deletions and 
numerous nonsense mutations are suggestive of haploinsufficiency as the 
disease-causing mechanism. No genotype phenotype correlation was apparent.