title: Arrhythmogenic right ventricular cardiomyopathy caused by deletions in plakophilin-2 and plakoglobin (Naxos disease) in families from Greece and Cyprus: genotype-phenotype relations, diagnostic features and prognosis.
abstract: OBJECTIVE
  To evaluate clinical disease expression, non-invasive diagnosis, and prognosis in families with dominant vs. recessive arrhythmogenic right ventricular cardiomyopathy (ARVC) due to mutations in related desmosomal proteins plakophilin-2 (PKP2) and plakoglobin (JUP), respectively.
  
  
  RESULTS
  One hundred and eighty-seven individuals belonging to ARVC families, four with dominant PKP2 mutations and 12 with recessive JUP mutation underwent serial non-invasive cardiac assessment. Survival and arrhythmic events were evaluated prospectively up to 21 years (median 8.5 years). Sixteen of 22 PKP2 carriers and all 26 homozygous JUP carriers fulfilled the diagnostic criteria for ARVC, the youngest by the age of 13 years. Clinical disease expression did not differ significantly between PKP2 and JUP carriers. T-wave inversion in leads V1-V3, right ventricular wall motion abnormalities, and frequent ventricular extrasystoles were the most sensitive/specific markers for identification of mutation carriers. QRS dispersion > or =40 ms was an independent predictor of syncope but not of sudden death.
  
  
  CONCLUSIONS
  Mutations in PKP2 and JUP express similar cardiac phenotype. Non-invasive family screening may largely be based on T-wave inversion, right ventricular wall motion abnormalities, and frequent ventricular extrasystoles to identify mutation carriers.
authors.affiliation: Department of Cardiology, Nicosia General Hospital, Nicosia, Cyprus.
authors.forename: Loizos
authors.initials: L
authors.lastname: Antoniades
authors.forename: Adalena
authors.initials: A
authors.lastname: Tsatsopoulou
authors.forename: Aris
authors.initials: A
authors.lastname: Anastasakis
authors.forename: Petros
authors.initials: P
authors.lastname: Syrris
authors.forename: Angeliki
authors.initials: A
authors.lastname: Asimaki
authors.forename: Demosthenes
authors.initials: D
authors.lastname: Panagiotakos
authors.forename: Costas
authors.initials: C
authors.lastname: Zambartas
authors.forename: Christodoulos
authors.initials: C
authors.lastname: Stefanadis
authors.forename: William J
authors.initials: WJ
authors.lastname: McKenna
authors.forename: Nikos
authors.initials: N
authors.lastname: Protonotarios
mesh_terms: D000293:Adolescent; D000328:Adult; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D003535:Cyprus / Q000208:ethnology; D018572:Disease-Free Survival; D004452:Echocardiography; D015716:Electrocardiography, Ambulatory; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006115:Greece / Q000208:ethnology; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D051191:Plakophilins / Q000235:genetics*; D011379:Prognosis; D018570:Risk Assessment; D051185:gamma Catenin / Q000235:genetics*
chemical_list: D051191:Plakophilins; D051185:gamma Catenin