title: A family with a complex clinical presentation characterized by arrhythmogenic right ventricular dysplasia/cardiomyopathy and features of branchio-oculo-facial syndrome.
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 4.4 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.
authors: Division of Cardiology, Johns Hopkins University, Baltimore, Maryland, USA.
authors: Brittney
authors: B
authors: Murray
authors: Rohan
authors: R
authors: Wagle
authors: Nuria
authors: N
authors: Amat-Alarcon
authors: Alisha
authors: A
authors: Wilkens
authors: Paul
authors: P
authors: Stephens
authors: Elaine H
authors: EH
authors: Zackai
authors: Elizabeth
authors: E
authors: Goldmuntz
authors: Hugh
authors: H
authors: Calkins
authors: Matthew A
authors: MA
authors: Deardorff
authors: Daniel P
authors: DP
authors: Judge
mesh_terms: D000328:Adult; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000000981:diagnostic imaging* / Q000235:genetics / Q000503:physiopathology; D019280:Branchio-Oto-Renal Syndrome / Q000000981:diagnostic imaging* / Q000235:genetics / Q000503:physiopathology; D002872:Chromosome Deletion; D002896:Chromosomes, Human, Pair 6; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D025202:Molecular Diagnostic Techniques; D010375:Pedigree; D010641:Phenotype; D013318:Stroke Volume; D014463:Ultrasonography