Microdeletions of 5.5Mb (4q13.2-q13.3) and 4.1Mb (7p15.3-p21.1) associated with a saethre-chotzen-like phenotype, severe intellectual disability, and autism

• Published in: American journal of medical genetics. Part A 2013-08, Vol.161 (8), p.2078-2083
• Main Authors: Shimada, Shino, Okamoto, Nobuhiko, Nomura, Shohei, Fukui, Miho, Shimakawa, Shuichi, Sangu, Noriko, Shimojima, Keiko, Osawa, Makiko, Yamamoto, Toshiyuki
• Format: Article
• Language: English
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.36027

We observed a patient with a Saethre-Chotzen-like phenotype with severe neurological features. Saethre-Chotzen syndrome (acrocephalosyndactyly type III; SCS; OMIM #101400) is an autosomal dominant craniosynostosis syndrome characterized by craniofacial and mild limb abnormalities. The phenotypic features of chromosomal microdeletions involving the 7p21.1, where the twist homolog 1 gene (TWIST1) responsible for SCS is located, are recognized as a contiguous gene deletion syndrome with SCS and other phenotypic manifestations. In this study, we identified microdeletions in 4q13.2 and 7p21.1 in a patient with SCS and severe neurological features including developmental delay and autistic behavior. In comparison to other SCS patients with intragenic mutations or small deletions in 7p21.1, neurological features seen in this patient were extremely severe, likely modified by a concurrent deletion of 4q13.2. Both microdeletions were de novo and paternal in origin. Further information on such concurrent chromosomal deletions should be accumulated for better understanding of the mechanism. © 2013 Wiley Periodicals, Inc. [PUBLICATION ABSTRACT]