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.
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.
Antoniades
Loizos
L
Department of Cardiology, Nicosia General Hospital, Nicosia, Cyprus.
Tsatsopoulou
Adalena
A
Anastasakis
Aris
A
Syrris
Petros
P
Asimaki
Angeliki
A
Panagiotakos
Demosthenes
D
Zambartas
Costas
C
Stefanadis
Christodoulos
C
McKenna
William J
WJ
Protonotarios
Nikos
N
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*
D051191:Plakophilins; D051185:gamma Catenin