BACKGROUND: Saethre-Chotzen syndrome is a craniosynostosis syndrome further 
characterized by distinctive facial and limb abnormalities. It shows complete 
penetrance and variable expressivity and has been linked to the TWIST gene on 
chromosome 7p21; more than 80 different intragenic mutations and, recently, 
large deletions have been detected in Saethre-Chotzen patients. The aim of this 
study was to genetically and phenotypically characterize patients with a 
clinical diagnosis of Saethre-Chotzen syndrome.
METHODS: Patients with a clinical diagnosis as well as those with a genetic 
diagnosis of Saethre-Chotzen syndrome (n = 34) were included in the study.
RESULTS: The study showed that the important features of Saethre-Chotzen 
syndrome are brachycephaly (occurring in 74 percent of patients), a broad, 
depressed nasal bridge (65 percent), a high forehead (56 percent), ptosis (53 
percent), and prominent auricular crura (56 percent). Furthermore, using 
different molecular techniques, pathogenic mutations in the TWIST gene were 
identified in 71 percent of patients.
CONCLUSIONS: Patients with deletions of the TWIST gene did not differ from those 
with intragenic TWIST mutations in frequency or severity of craniofacial 
abnormalities. However, they did distinguish themselves by the presence of many 
additional anomalies and diseases and--most importantly--the high frequency of 
mental retardation, which was borderline significant. The authors conclude that 
when using stringent inclusion criteria for studies of Saethre-Chotzen syndrome, 
patients who have a pathogenic mutation of the TWIST gene should be excluded.