In this study two Italian families comprising eight and four individuals, respectively, were investigated. Two individuals in the first and one individuals in the second family have been diagnosed with arrhythmogenic cardiomyopathy (ACM) according to the diagnostic task force criteria  (Table 1). Furthermore, previous clinically certified molecular tests on known ACM related genes have identified PKP2 variants in all affected and some healthy family members (Fig. 1).Table 1Clinical characteristics of studied individualsa FamilyIDGenderAgePhysical exerciseAffected by ACMType of first symptomAge at first symptomDiagnosed ACM mutationICDACM TherapyDysfunction and structural alterationsTissue characteristic of wallRepolarization abnormalitiesDepolarization or conduction abnormalitiesArrhythmiasComorbiditiesFam1Fam1.I.2F87nono––NM_004572.3(PKP2):c.2013delCnononenonen.a.nonenonenonehypertentionFam1.II.1M70nono – – – nononen.a.n.a.nonenonenonehyperlipidemiaFam1.II.2F67nono––NM_004572.3(PKP2):c.2013delCnononenonen.a.minornonenonehyperlipidemiaFam1.II.3F62nono–––nononen.a.n.a.nonenonenonehyperlipidemiaFam1.II.4M68nono–––nononen.a.n.a.nonenonenonemyocardial infarctionFam1.III.1M39yesno––NM_004572.3(PKP2):c.2013delCnononenonen.a.minornonenonenoneFam1.III.2M35noyesVT21NM_004572.3(PKP2):c.2013delCyesSotalolmajorn.a.majormajormajorhyperlipidemiaFam1.III.3F31yesyesSyncope17NM_004572.3(PKP2):c.2013delCyesSotalolmajorn.a.majornonemajornoneFam2Fam2.I.1M67nono–––nononen.a.n.a.nonenonenonenoneFam2.I.2F66nono––NG_009000.1(PKP2):c.2569_2577 + 41delnononenonen.a.minornonenoneatrial fibrillationFam2.II.1M34yesyesSyncope24NG_009000.1(PKP2):c.2569_2577 + 41delyesSotalolminorn.a.majormajormajornoneFam2.II.2M41yesno––NG_009000.1(PKP2):c.2569_2577 + 41delnononenonen.a.nonenonenonenone aIndividuals classified as they reach major or minor diagnostic criteria n.a.: not available; VT: Ventricular Tachycardia; ICD: implantable cardioverter defibrillator; Athletic lifestyle: defined as intense sportive activity more than 3 times a week Fig. 1Pedigrees of the two families analyzed in this study. Only labeled individuals were sequenced. +: Heterozygous variant, filled black symbols: affected individuals; white symbols with +: carrier individuals; white empty symbols: healthy individuals. Left: Family 1 (Fam1); the blue + symbol indicates the presence of the NM_004572.3(PKP2):c.2013delC variant, the orange + symbol indicates the presence of the four Fam1 variants ENSP00000312435.2(DAG1):p.Leu86Phe, ENSP00000263347.7(TCF25):p.Ser390Phe, ENSP00000259371.2(DAB2IP):p.Asp10Gly, ENSP00000357816.5(CTBP2):p.Gly70Arg. Right: Family 2 (Fam2); the pink + symbol indicates the presence of the NG_009000.1(PKP2):c.2569_2577 + 41del variant, the green + symbol indicates the presence of the ENSP00000434586.1(TTN):p.Gln24857His and the ENSP00000434586.1(TTN):p.Arg23483His variants