Saethre-Chotzen syndrome is a common craniosynostosis syndrome characterized by 
craniofacial and limb anomalies. Intragenic mutations of the TWIST gene within 
7p21 have been identified as a cause of this disorder. There is phenotypic 
overlap with other craniosynostosis syndromes, and intragenic mutations in FGFR2 
(fibroblast growth factor receptor 2) and FGFR3 (fibroblast growth factor 
receptor 3) have been demonstrated in the other conditions. Furthermore, 
complete gene deletions of TWIST have also been found in a significant 
proportion of patients with Saethre-Chotzen syndrome. We investigated 11 
patients clinically identified as having the Saethre-Chotzen phenotype and 4 
patients with craniosynostosis but without a clear diagnosis. Of the patients 
with the Saethre-Chotzen phenotype, four were found to carry the FGFR3 P250R 
mutation, three were found to be heterozygous for three different novel 
mutations in the coding region of TWIST, and two were found to have a deletion 
of one copy of the entire TWIST gene. Developmental delay was a distinguishing 
feature of the patients with deletions, compared to patients with intragenic 
mutations of TWIST, in agreement with the results of Johnson et al. [1998: Am J 
Hum Genet 63:1282-1293]. No mutations were found for the four patients with 
craniosynostosis without a clear diagnosis. Therefore, 9 of our 11 patients 
(82%) with the Saethre-Chotzen phenotype had detectable genetic changes in FGFR3 
or TWIST. We propose that initial screening for the FGFR3 P250R mutation, 
followed by sequencing of TWIST and then fluorescence in situ hybridization 
(FISH) for deletion detection of TWIST, is sufficient to detect mutations in > 
80% of patients with the Saethre-Chotzen phenotype.