A family with a complex clinical presentation characterized by arrhythmogenic right ventricular dysplasia/cardiomyopathy and features of branchio-oculo-facial syndrome

Brittney Murray, Rohan Wagle, Nuria Amat-Alarcon, Alisha Wilkens, Paul Stephens, Elaine H. Zackai, Elizabeth Goldmuntz, Hugh Calkins, Matthew A. Deardorff, Daniel P. Judge

Research output: Contribution to journalArticlepeer-review

Abstract

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 4.4Mb 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.

Original languageEnglish (US)
Pages (from-to)371-376
Number of pages6
JournalAmerican Journal of Medical Genetics, Part A
Volume161
Issue number2
DOIs
StatePublished - Feb 2013

Keywords

  • Arrhythmogenic right ventricular dysplasia/cardiomyopathy
  • Branchio-oculo-facial syndrome
  • Chromosome microarray analysis
  • Contiguous deletion

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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