Presented at the 50th Anniversary Meeting of the Japanese Teratology Society, Awaji Island, July, 2010.
Role of rare cases in deciphering the mechanisms of congenital anomalies: CHARGE syndrome research
Article first published online: 21 FEB 2011
© 2011 The Author. Congenital Anomalies © 2011 Japanese Teratology Society
Volume 51, Issue 1, pages 12–15, March 2011
How to Cite
Kosaki, K. (2011), Role of rare cases in deciphering the mechanisms of congenital anomalies: CHARGE syndrome research. Congenital Anomalies, 51: 12–15. doi: 10.1111/j.1741-4520.2010.00309.x
- Issue published online: 21 FEB 2011
- Article first published online: 21 FEB 2011
- Accepted manuscript online: 15 DEC 2010 08:19AM EST
- Received November 11, 2010; revised and accepted December 6, 2010.
- CHARGE syndrome;
- London Dysmorphology Database;
- methimazole embryopathy
In this review, our work on CHARGE syndrome will be used to exemplify the role of rare cases in birth defects research. The analysis of 29 cases with mutations of CHD7, the causative gene for CHARGE syndrome, clarified the relative importance of the cardinal features, including facial nerve palsy and facial asymmetry. Concurrently, in situ hybridization using chick embryos studies were performed to delineate the expression pattern of Chd7. The Chd7-positive regions in the chick embryos and the anatomical defects commonly seen in patients with CHARGE syndrome were well correlated: expression in the optic placode corresponded with defects such as coloboma, neural tube with mental retardation, and otic placode with ear abnormalities. The correlation between expression in the branchial arches and nasal placode with the clinical symptoms of CHARGE syndrome, however, became apparent when we encountered two unique CHARGE syndrome patients: one with a DiGeorge syndrome phenotype and the other with a Kallman syndrome phenotype. A unifying hypothesis that could explain both the DiGeorge syndrome phenotype and the Kallman syndrome phenotype in patients with CHARGE syndrome may be that the mutation in CHD7 is likely to exert its effect in the common branch of the two pathways of neural crest cells. As exemplified in CHARGE syndrome research, rare cases play a critical role in deciphering the mechanisms of human development. Close collaboration among animal researchers, epidemiologists and clinicians hopefully will enhance and maximize the scientific value of rare cases.