None of the authors report any potential conflict of interest regarding this manuscript.
Article first published online: 10 JAN 2013
Copyright © 2013 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 161, Issue 2, pages 371–376, February 2013
How to Cite
Murray, B., Wagle, R., Amat-Alarcon, N., Wilkens, A., Stephens, P., Zackai, E. H., Goldmuntz, E., Calkins, H., Deardorff, M. A. and Judge, D. P. (2013), A family with a complex clinical presentation characterized by arrhythmogenic right ventricular dysplasia/cardiomyopathy and features of branchio-oculo-facial syndrome. Am. J. Med. Genet., 161: 371–376. doi: 10.1002/ajmg.a.35733
How to Cite this Article: Murray B, Wagle R, Amat-Alarcon N, Wilkens A, Stephens P, Zackai EH, Goldmuntz E, Calkins H, Deardorff MA, Judge DP. 2013. A family with a complex clinical presentation characterized by arrhythmogenic right ventricular dysplasia/cardiomyopathy and features of branchio-oculo-facial syndrome. Am J Med Genet Part A 161A:371–376.
- Issue published online: 24 JAN 2013
- Article first published online: 10 JAN 2013
- Manuscript Accepted: 1 OCT 2012
- Manuscript Received: 9 APR 2012
- NIH/NICHD. Grant Number: K08HD055488
- Johns Hopkins ARVD Program
- Bogle Foundation
- Campanella family
- Wilmerding Endowment
- Dr. Francis P Chiaramonte Foundation
- Healing Hearts Foundation
- St. Jude Medical Foundation, Medtronic, Inc.
- Boston Scientific Corp
- arrhythmogenic right ventricular dysplasia/cardiomyopathy;
- branchio-oculo-facial syndrome;
- contiguous deletion;
- chromosome microarray analysis
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a familial form of cardiomyopathy typically caused by mutations in genes that encode an element of the cardiac desmosome. Branchio-oculo-facial syndrome (BOFS) is a craniofacial disorder caused by TFAP2A mutations. In a family segregating ARVD/C, some members also had features of BOFS. Genetic testing for ARVD/C identified a mutation in PKP2, encoding plakophilin-2, a component of the cardiac desmosome. Evaluation of dysmorphology by chromosome microarray (CMA) identified a 4.4 Mb deletion at chromosome 6p24 that included both TFAP2A and DSP, encoding desmoplakin, an additional component of the cardiac desmosome implicated in ARVD/C. A family member with both the 6p24 deletion and PKP2 mutation had more severe cardiac dysfunction. These findings suggest that this contiguous gene deletion contributes to both ARVD/C and BOFS, and that DSP haploinsufficiency may contribute to cardiomyopathy. This family provides a clinical example that underscores the need for careful evaluation in clinical scenarios where genetic heterogeneity is known to exist. Finally, it suggests that individuals with unexplained cardiomyopathy and dysmorphic facial features may benefit from CMA analysis. © 2013 Wiley Periodicals, Inc.