Saethre-Chotzen syndrome: a case report.
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.
Division of Pediatric Dentistry, Department of Orofacial Sciences, School of Dentistry, University of California at San Francisco, San Francisco, California, USA.
William A
WA
Peña
Anne
A
Slavotinek
Snehlata
S
Oberoi
D000168:Acrocephalosyndactylia / Q000235:genetics*; D002648:Child; D005260:Female; D006801:Humans; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D051879:Twist-Related Protein 1 / Q000235:genetics*
D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1