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Nikos Protonotarios

Publications and source records attributed to Nikos Protonotarios.

6 recordsLinked to original sources
PubMed2006

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.

AIMS: 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. METHODS AND 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. CONCLUSION: 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.

Adolescent↗
PubMed2006

Naxos disease: cardiocutaneous syndrome due to cell adhesion defect.

Naxos disease is a recessively inherited condition with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) and a cutaneous phenotype, characterised by peculiar woolly hair and palmoplantar keratoderma. The disease was first described in families originating from the Greek island of Naxos. Moreover, affected families have been identified in other Aegean islands, Turkey, Israel and Saudi Arabia. A syndrome with the same cutaneous phenotype and predominantly left ventricular involvement has been described in families from India and Ecuador (Carvajal syndrome). Woolly hair appears from birth, palmoplantar keratoderma develop during the first year of life and cardiomyopathy is clinically manifested by adolescence with 100% penetrance. Patients present with syncope, sustained ventricular tachycardia or sudden death. Symptoms of right heart failure appear during the end stages of the disease. In the Carvajal variant the cardiomyopathy is clinically manifested during childhood leading more frequently to heart failure. Mutations in the genes encoding the desmosomal proteins plakoglobin and desmoplakin have been identified as the cause of Naxos disease. Defects in the linking sites of these proteins can interrupt the contiguous chain of cell adhesion, particularly under conditions of increased mechanical stress or stretch, leading to cell death, progressive loss of myocardium and fibro-fatty replacement. Implantation of an automatic cardioverter defibrillator is indicated for prevention of sudden cardiac death. Antiarrhythmic drugs are used for preventing recurrences of episodes of sustained ventricular tachycardia and classical pharmacological treatment for congestive heart failure, while heart transplantation is considered at the end stages.

Adolescent↗
PubMed2005

Naxos disease.

Since 1995, according to the World Health Organisation's classification of cardiomyopathies, Naxos disease has been considered as the recessive form of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). It is a stereotype association of ARVD/C with a cutaneous phenotype, characterised by woolly hair and palmoplantar keratoderma.

Journal Article↗
PubMed2004

Remodeling of myocyte gap junctions in arrhythmogenic right ventricular cardiomyopathy due to a deletion in plakoglobin (Naxos disease).

OBJECTIVES: We tested the hypothesis that defective interactions between adhesion junctions and the cytoskeleton caused by the plakoglobin mutation in Naxos disease lead to remodeling of gap junctions and altered expression of the major gap junction protein, connexin43. BACKGROUND: Naxos disease, a recessive form of arrhythmogenic right ventricular cardiomyopathy, is associated with a high incidence of arrhythmias and sudden cardiac death. Naxos disease is caused by a mutation in plakoglobin, a protein that links cell-cell adhesion molecules to the cytoskeleton. METHODS: Myocardial expression of connexin43 and other intercellular junction proteins was characterized in 4 patients with Naxos disease. Immunohistochemistry was performed in all 4 patients, and immunoblotting and electron microscopy were performed in 1 patient who died in childhood before overt arrhythmogenic right ventricular cardiomyopathy had developed. RESULTS: Connexin43 expression at intercellular junctions was reduced significantly in both right and left ventricles in all patients with Naxos disease. Electron microscopy revealed smaller and fewer gap junctions interconnecting ventricular myocytes. Mutant plakoglobin was expressed but failed to localize normally at intercellular junctions. Localization of N-cadherin, alpha- and beta-catenins, plakophilin-2, desmoplakin-1, and desmocollin-2 at intercalated disks appeared normal. CONCLUSIONS: Remodeling of gap junctions occurs early in Naxos disease, presumably because of abnormal linkage between mechanical junctions and the cytoskeleton. Gap junction remodeling may produce a coupling defect which, combined with the subsequent development of pathologic changes in myocardium, could contribute to a highly arrhythmogenic substrate and enhance the risk of sudden death in Naxos disease.

Adult↗
PubMedDate not supplied

Naxos disease and Carvajal syndrome: cardiocutaneous disorders that highlight the pathogenesis and broaden the spectrum of arrhythmogenic right ventricular cardiomyopathy.

Naxos disease is a recessive association of arrhythmogenic right ventricular cardiomyopathy (ARVC) with wooly hair and palmoplantar keratoderma or similar skin disorder. The clinical and histopathological spectrum of heart disease, molecular genetics and genotype-phenotype correlation are reviewed in 22 affected families with this cardiocutaneous syndrome reported in the literature from Greece, Italy, India, Ecuador, Israel and Turkey. All patients had the hair and skin phenotype from infancy and developed ARVC by adolescence. Mutations in genes encoding the cell adhesion proteins piakoglobin and desmoplakin that truncate the proteins at the C-terminal domains were identified to underlie this syndrome. A particular mutation in Ecuadorian families that truncates the intermediate filament-binding site of desmoplakin results in a variant of Naxos disease with predominantly left ventricular involvement, early morbidity and clinical overlapping with dilated cardiomyopathy (Carvajal syndrome). A lethal autosomal recessive cardiocutaneous syndrome of Poll Hereford calves has been reported in Australia sharing similarities with the human syndrome reviewed here with respect to hair and cardiac phenotype. The cardiomyopathy in Naxos cardiocutaneous syndromes presents with increased arrhythmogenicity and variable left ventricular involovement and is characterized histologically by myocardial loss with fibrofatty or fibrous replacement at subepicardial and mediomural layers. The clinical heterogeneity and tissue characteristics in this cell-adhesion cardiomyopathy might be mutation specific and leads to consideration that the spectrum of ARVC should be broadened.

Abnormalities, Multiple↗