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.