**9. Cardiomyopathy in muscular dystrophies**

Muscular dystrophies are a heterogeneous group of inherited disorders, characterized by progressive weakness and wasting of the skeletal muscles. They are generally associated with cardiomyopathy. In many cases, there is no correlation between the skeletal myopathy and the involvement of the heart. The mutations of the genes that cause muscular dystrophies affect the skeletal and/or cardiac muscles. These include proteins which are associated with the dystrophin–glycoprotein complex, the nuclear lamina or the sarcomere (Hermans, 2012).

Cardiomyopathy occurs in myofibrillar myopathy, myotonic dystrophies, myotonic myopa‐ thies, dystrophinopathies, Emery-Dreifuss muscular dystrophy, and limb girdle muscular dystrophies (Hermans, 2012).

They are inherited in autosomal dominant, autosomal recessive and X-linked mode. (See Table 4, Table 5).

The different forms of muscular dystrophies vary in the age of onset with no male or female prevalence and have different clinical features and severity. Mutations in the genes that are involved muscular dystrophies can cause hypertrophic, dilated or restrictive cardiomyopathy, but most cardiomyopathies in patients with a muscular dystrophy are of the dilated type. The progression of the disorders and life expectancy vary widely, even among different members of the same family. Patients die of sudden death due to conduction defects, and heart failure.

In dystrophinopathies, sarcoglycanopathies, and the disorders that are linked to mutations in the fukutin-related protein, the feature that stands out is the cardiomyopathy the patients suffer. In muscular dystrophies, the patients usually have a dilated cardiomyopathy. Hyper‐ trophic cardiomyopathy can be observed in Danon disease, α-B crystallinopathy, and on patients or carriers of DMD and BMD. (De Ambroggi, 1995, Vicart 1998; Nguyen, 1998; Lazarus, 1999; Melacini, 1999; Barresi, 2000; Politano, 2001; Selcen, 2003; Fanin, 2001; Jefferies, 2005; Nakanishi, 2006; Connuck, 2008; Kaspar, 2009; Goldfarb, 2009; Lilienbaum, 2012; Hermans, 2012)

and the disorders can appear at any age. All the mitochondria have multiple copies of their own mtDNA and the mutation rate is much higher than in nuclear DNA (Walter, 2000;

Many mitochondrial disorders involve multiple organ systems such as the brain, the heart, the liver, and the skeletal muscles which are, therefore, affected due to the fact they depend on the energy and they are especially susceptible to energy metabolism impairment (Walter, 2000;

Mitochondrial dysfunction and clinical symptoms appear when the heteroplasmic levels are

above 80%-90% (Walter, 2000; Carrasco, 2005; De Jonge, 2011).

Carrasco, 2005; De Jonge, 2011).

**Disease Name Gene Symbol Locus**

*(TTID)*

Myotilinopathy Myotilin *MYOT*

BCL2 associated athanogen 3

myotoninprotein kinase (Mt-PK).

zinc finger protein-9 gene

**Table 4.** Genes that cause cardiomyopathy in muscular dystropies

Alpha-B crystallinopathy

*BAG3*-Related Myofibrillar Myopathy

Myotonic dystrophy

Myotonic dystrophy

Duchenne/Becker muscular dystrophy

Emery-Dreyfuss Muscular

Dystrophy1,X-linked

type 1

type 2

**name**

Desminopathy Desmin *DES* MFM1 **2q35** Desmin AD/AR

ZASPopathy ZASP *LDB3* MFM4 **10q23.2** LIM domain-binding

Filaminopathy FilaminC *FLNC* MFM5 7q32.1 Filamin C AD

**Chromosome locus**

MFM3 5q31.2 Myotilin

CRYAB gene *CRYAB* MFM2 11q23.1 alpha-B-crystallin AR/AD

*BAG3* BAG3 *10q26.11* BAG family

*DMPK* DMPK 19q13.3 dystrophia

*CNBP 3q21.3* zinc finger protein-9AD

dystrophin *DMD* DMD Xp21.2 dystrophin X-linked

EMD gene *EMD* EMD1 Xq28 emerin X-linked

**Protein Mode of**

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

(titinmmunoglobuli n domain protein)

protein 3

molecular chaperone regulator 3

kinase

myotonica-protein

**inheritance**

117

AD

AD

AD

AD

Carrasco, 2005; De Jonge, 2011).
