**5. Arrhythmogenic right ventricular cardiomyopathy / dysplasia**

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/ARVD) is a commonly inherited disorder with a family history in 30 to 50% of the cases (Klauke, 2010).

The prevalence has been estimated 1:2000 to 1:5000 in the general population (Peters 2006, Cox&Hauer, 2011).

ARVC is characterized by fibro-fatty replacement of the myocardium with a marked involve‐ ment of the right ventricle. ARVC can be defined by the presence either sectored or global right ventricular dysfunction. The left ventricular abnormalities which lead to DCM may take place later. Clinical features include tachyarrhythmias, electrocardiographic abnormalities, systolic heart failure, syncope and sudden death. ARVC is a frequent cause of sudden death in young people and athletes (Maron, 2006).

It is transmitted with an autosomal dominant pattern, though autosomal recessive families have also been reported. Incomplete penetrance and great variability in the symptoms have been observed (Hamid, 2002; Awad, 2008; Eliott, 2008; Klauke, 2010, Cox&Hauer, 2011).

Desmosomes are intercellular junctions that link intermediate filaments to the plasma membrane and are essential to tissues that experience mechanical stress such as the myocar‐ dium. Mutations in the cardiac desmosome genes are to be held responsible for most of the cases that cause the disorder. (See Table 3)

The mutations p.S13F, p.E114del and p.N116S in the desmin gene have the same ARVC cardiac phenotype. In transfection cells aggresome formation in the cytoplasm was observed (Van Titelen, 2007; Vernengo, 2010; Klauke, 2010). Only recently has it been proven that seven members of the Swedish family with ARVC7 had the p.Pro419Ser mutation in *DES*, instead of a mutation linked to chromosome 10q23.2 (Melberg, 1999; Hedberg, 2012).

trabeculations and intertrabecular recesses (Hermida-Prieto, 2004; Freedom, 2005; Budde,

transmembrane protein 43 *TMEM43* ARVD5 3p25 .1 Transmembrane protein 43

Mutations in several genes coding for sarcomeric proteins have been described in NCCM, such as β-myosin heavy chain (*MYH7*), cardiac myosin-binding protein C (*MYBPC3*), α-cardiac actin (*ACTC1*), cardiac troponin T (*TNNT2*), α-tropomyosin (*TPM1*) and cardiac troponin I (*TNNI3).* MYH7 has been reported to be the most frequent disease gene in NCCM in the

Takotsubo cardiomyopathy is characterized by an acute but transitient LV systolic dysfunction without atherosclerotic coronary artery disease and it is triggered by psychological stress

The cell membrane transit of sodium and potassium ions is ruled by the ion channel genes which encode proteins responsible for the right transit of these ions. Mutations in these

The majority of the patients have an autosomal dominant mode of inheritance.

Desmin *DES* ARVC 2q35 Desmin

**ARCV gene Symbol Locus name Chromosome locus Protein**

Ryanodine receptor 2 *RYR2* ARVD2 1q43 RYR2 Unknown Unknown ARVD3 14q12-q22 Unknown Unknown Unknown ARVD4 2q32 .1-q32.3 Unknown

Unknown Unknown ARVD6 10p14-p12 Unknownn Desmin *DES* ARVD7 2q35 Desmin Desmoplakin *DSP* ARVD8 6p24 .3 Desmoplakin Plakophilin-2 *PKP2* ARVD9 12p11 .21 Plakophilin-2 Desmoglein-2 *DSG2* ARVD10 18q12 .1 Desmoglein-2 Desmocollin-2 *DSC2* ARVD11 18q12 .1 Desmocollin-2 Junction plakoglobin *JUP* ARVD12 17q21 .2 Junction plakoglobin

*TGFB3* ARVD1 14q2 Transforming growth factor

beta-3

The Role of Genetics in Cardiomyopathy http://dx.doi.org/10.5772/55775 113

absence of HCM (Ichida, 2001; Hermida-Prieto. 2004; Vatta, 2003; Shan, 2008).

2007; Monserrat, 2007; Klaassen, 2008)

**Table 3.** Genes that cause ARVC.

Transforming growth factor

beta- 3

**7. Takotsubo cardiomyopathy**

(Sharkey, 2005; Sealove, 2008).

**8. Ion channel disorders**

Naxos disease and Carvajal disease are ARVC inherited in an autosomal recessive pattern. The former is caused by mutations in the plakoglobin gene on chromosome 17q21,2 and the latter by mutations in the desmoplakin gene on chromosome 6p24 (Protonotarios, 1986; McKoy, 2000; Schonberger, 2001; Cox&Hauer, 2011).
