Clinical and genetic analysis of patients with Saethre-Chotzen syndrome.
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.
de Heer
Inge Marieke
IM
Department of Plastic and Reconstructive Surgery, Erasmus Medical Center, Rotterdam, The Netherlands.
de Klein
Annelies
A
van den Ouweland
Ans M
AM
Vermeij-Keers
Christl
C
Wouters
Cokkie H
CH
Vaandrager
Jan Michiel
JM
Hovius
Steven E R
SE
Hoogeboom
Jeannette M
JM
D000168:Acrocephalosyndactylia / Q000175:diagnosis / Q000235:genetics*; D002872:Chromosome Deletion; D004251:DNA Transposable Elements; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D051879:Twist-Related Protein 1 / Q000235:genetics*
D004251:DNA Transposable Elements; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1