**1. Introduction**

Cardiomyopathies are categorized based on their phenotype. In that context, dilated cardiomyopathy (DCM) is characterized by a dilated left ventricle (LV), typically with thin walls, and systolic dysfunction (**Figure 1**). Sometimes the dysfunction is not limited to the left ventricle but also affects the right ventricle. It is estimated that approximately 1 in 2500 people suffer from DCM [1]. The causative pathways are often complex, and several risk factors work together. In the vast majority of patients, there is a history of hypertension. Other well-known etiologies are myocarditis, chemotherapy, toxins, radiation, and coronary artery disease. However, when a causative reason for the dilation of the heart cannot be identified, DCM is considered idiopathic. About 20–50% of idiopathic DCM is considered to be of a genetic origin, being consequently hereditary [2]. Interestingly, only in 30–40% of cases of familial DCM can a specific gene be identified [3].

In hereditary DCM, there is variability among phenotypes, and the manifestation of LV dysfunction is heterogeneous. More than 50 genes are associated with the disease [4] (**Table 1**). Many of the gene mutations responsible for DCM affect the cell structure called sarcomere, which is involved in cardiac contractility. That is why some of those genes may be responsible for the development of hypertrophic cardiomyopathy as well. In 20% of the cases of hereditary DCM, mutations of the titin (TTN) gene are found, which encodes the protein titin found in the sarcomere [5].

#### **Figure 1.**

*Normal and dilated left ventricle in parasternal short-axis view.*

The inheritance pattern is autosomal dominant in the vast majority of the cases, which means that an individual has a 50% chance to inherit the gene if one of the parents carries it. In other cases, the pattern is autosomal recessive, which means that if both parents are affected, there is a 25% chance of inheriting the disease genotype. X-linked patterns, in which the gene is inherited through an X chromosome, have also been reported. In some cases, it is possible that the carrier may not develop the phenotype of the disease due to variable penetrance of the disease.

Inherited DCM is defined by (a) the presence of two or more affected individuals in a single family who fulfill DCM criteria; fractional shortening <25% and/or ejection fraction <45% and left ventricular end diastolic diameter > 117% of the upper reference level corrected for age and body surface area based on Henry's formula or (b) the presence of a first-degree relative with unexplained sudden death before the age of 35 years [6].

Symptoms of DCM are due to ventricular dysfunction and compensatory left ventricular remodeling as well as the involvement of the electrical conduction system of the heart [7]. Symptoms vary among patients, even if they are members of

**159**

**Table 1.**

the same family [5]. Symptoms can occur at any age; typically, they first appear in mid-adulthood. Patients often report breathlessness, swelling of the legs, fatigue, chest pain, and arrhythmias, ranging from palpitations and syncope to fatal

*The main genes associated with hereditary dilated cardiomyopathy and the cellular structure that they regulate.*

*Sudden Cardiac Death in Hereditary Dilated Cardiomyopathy*

BAG3 Sarcomere CRYAB Cytoskeleton

DES Cytoskeleton DMD Cytoskeleton DSG2 Desmosome EYA4 Other FLNC Cytoskeleton GATAD1 Other

LCB3 Cytoskeleton LMNA Nuclear envelope MYBPC3 Sarcomere MYH6 Sarcomere MYH7 Sarcomere MYPN Cytoskeleton

PSEN1 Other PSEN2 Other RBM20 Other

SGCD Cytoskeleton TAZ Other

TMPO Nuclear envelope TNNC1 Sarcomere TNNI3 Sarcomere TNNT2 Sarcomere TPM1 Sarcomere TTN Sarcomere

CSRP3 Sarcomere and cytoskeleton

LAMA4 Extracellular matrix proteins

PLN Calcium/sodium handling

SCN5A Calcium/sodium handling

TCAP Sarcomere and cytoskeleton

VCL Sarcomere and cytoskeleton

**Gene Cellular structure** ABCC9 Calcium/sodium handling ACTC1 Sarcomere and cytoskeleton ACTN2 Sarcomere and cytoskeleton ANKRD1 Sarcomere and transcription factor

*DOI: http://dx.doi.org/10.5772/intechopen.91702*


#### *Sudden Cardiac Death in Hereditary Dilated Cardiomyopathy DOI: http://dx.doi.org/10.5772/intechopen.91702*

#### **Table 1.**

*The main genes associated with hereditary dilated cardiomyopathy and the cellular structure that they regulate.*

the same family [5]. Symptoms can occur at any age; typically, they first appear in mid-adulthood. Patients often report breathlessness, swelling of the legs, fatigue, chest pain, and arrhythmias, ranging from palpitations and syncope to fatal

arrhythmias that cause SCD. Unfortunately, SCD is sometimes the first manifestation of the disease.
