In this article, we describe a large five-generation family with characteristics of the Saethre-Chotzen syndrome as well as of the blepharophimosis ptosis epicanthus inversus syndrome. Segregating with their phenotype is a deletion of the chromosome 7p21 TWIST gene locus. The TWIST gene indeed is involved in Saethre-Chotzen syndrome, a craniosynostosis syndrome further characterized by specific facial and limb abnormalities. However, only two members of our family exhibited craniosynostosis. This report demonstrates that the genetics of craniofacial anomalies are less straightforward than they sometimes appear to be. Not only craniosynostosis, but also subtle facial deformities could be indicative of an abnormality of the TWIST gene. In conclusion, the clinical spectrum of genetic abnormalities of the TWIST gene is highly variable. We therefore recommend that genetic analysis of the TWIST gene locus, including fluorescence in situ hybridization, should be considered in familial cases of facial and eyelid abnormalities without the presence of craniosynostosis.

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Clinical Genetics: an international journal of genetics and molecular medicine
Department of Plastic and Reconstructive Surgery

de Heer, I. M., Hoogenboom, L. C. A., Eussen, B., Vaandrager, M., & de Klein, A. (2004). Deletion of the TWIST gene in a large five-generation family. Clinical Genetics: an international journal of genetics and molecular medicine, 65(5), 396–399. doi:10.1111/j.0009-9163.2004.00244.x