Saethre-Chotzen syndrome (acrocephalosyndactyly type III) is a craniosynostosis 
syndrome inherited in an autosomal dominant manner. Although similar to the 
other craniosynostosis syndromes in its clinical presentation, this syndrome is 
caused by a mutation in the TWIST1 gene. The TWIST1 gene product is a 
transcription factor containing a basic helix-loop-helix (bHLH) domain important 
in the development of the head and limbs. Clinical features of this syndrome 
include unilateral or bilateral coronal synostosis, ptosis, low-set ears, 
hearing loss, hypertelorism, maxillary hypoplasia, deviated nasal septum, broad 
great toes, clinodactyly, and syndactyly. We report a young girl with clinical 
features of Saethre-Chotzen syndrome who has a previously undescribed sequence 
variant in the TWIST1 gene, corresponding to p.R191M. The location of the 
altered amino acid in the Twist-box of TWIST1, the high conservation of this 
amino acid between different species, and the phenotype of the child all support 
a pathogenic role for this novel TWIST1 sequence alteration.