Cardiomyopathy familial

Most TTR variants are associated with extracellular deposition of amyloid fibrils in various tissue. These autosomal dominant hereditary amyloidoses include amyloidotic cardiomyopathy, familial amyloidotic polyneuropathy, and senile systemic amyloidosis. There is phenotypic variability (e.g., variable age of onset), suggesting that other factors may influence pathogenesis of the diseases. 

Other terms are encountered frequently in discussions of patients with cardiomyopathy. Familial cardiomyopathy is used to denote a condition found in more than one family member. Genetic predisposition may occur in aU three functional types. Ischemic cardiomyopathy is another frequently used term. Patients with occlusive atherosclerotic CAD and LV dysfunction are said to have ischemic cardiomyopathy. Ischemic cardiomyopathy is not a true cardiomyopathy because there is an identifiable cause of the ventricular muscle dysfunction. 

Troponin is a regulator of striated muscle contraction. Measurements of troponin I levels are routinely used in the diagnosis of myocardial infarction. In addition, mutations in the troponin I subunit are associated with familial hypertrophic cardiomyopathy. 

Sorcin is associated with the development of multidrug resistances in leukemia and other cancels. Sorcin is also able to improve cardiac contractility independently of (3-adienergic stimulation and may prove beneficial in treatment of heart failure. A point mutation in sorcin causes familial hypertrophic cardiomyopathy. 

Arrhythmogenic Right Ventricular Dysplasia/ Cardiomyopathy Aiteriogenesis Arteriosclerosis Arylhydrocarbon Receptor L-Ascorbic Acid ASF Family of Transporters Asn-linked Glycosylation ASON... 

In a previous section we mentioned the significance of myosin filament structure. In nematodes two forms of myosin-II, myosin A and B, are required for proper filament stmcture (Epstein, 1988). The two forms of myosin are expressed at the proper time to allow for correct filament assembly. An accessory protein called paramyosin is also required for correct filament assembly. In vertebrate cardiac muscle, there are also two isoforms of myosin-II a-myosin and p-myosin. The proper ratio of these two proteins is of utmost importance for proper muscle activity. The incorrect synthesis of a- and P-myosins results in a severe cardiac disorder known as hypertrophic cardiomyopathy. Genetic transmission of the disease occurs in about 55% of families. The inherited condition is called familial hypertrophic cardiomyopathy (FHC), and this condition is a leading cause of sudden death in young athletes. 

Geisterfer-Lowrance, A.A., Kass, S., Tanigawa, G., Vosberg, H.-P., McKenna, W., Seidman, C.E., Seidman, J.G. (1990). A molecular basis for familial hypertrophic cardiomyopathy a p-cardiac myosin heavy chain gene missense mutation. Cell 62, 999-1006,... 

Fatal infantile cytochrome c oxidase (CCO) deficiency is characterized by total absence of catalytic activity in skeletal muscle. This often occurs within the context of the Fanconi syndrome, or less commonly in association with a cardiomyopathy. Although the deficiency is global in skeletal muscle, with all fibers affected, only isolated scattered fibers show abnormal aggregations of mitochondria (ragged-red fibers). Multiple affected siblings within one family are frequently encountered and suggest autosomal recessive inheritance. The condition normally proves fatal before the age of six months and is characterized by worsening intractable lactic acidemia. 

Mutations in the Cardiac (i-Myosin Heavy Chain Gene Are One Cause of Familial Hypertrophic Cardiomyopathy... 

Figure 49-13. Simplified scheme of the causation of familial hypertrophic cardiomyopathy (MIM 192600) due to mutations in the gene encoding fi-myosin heavy chain. Mutations in genes encoding other proteins, such as the troponins, tropomyosin, and cardiac myosin-binding protein C can also cause this condition. Mutations in genes encoding yet other proteins (eg, dystrophin) are involved in the causation of dilated cardiomyopathy.

In short, the risks for HF are hypertension, atherosclerotic disease, diabetes mellitus, obesity, metabolic syndrome, use of cardiotoxins and a positive family history of cardiomyopathy. 

Zhang L et al A missense mutation in the CFIRM2 gene is associated with familial dilated cardiomyopathy. Circ Res 2008 102 1426. [PMID 18451336]... 

Adriamycin is an antibiotic of the family of anthracyclines with a wide spectrum of chemotherapeutic applications and anti-neoplasic action but it causes cardiotoxicity ranging from delayed and insidious cardiomyopathy to irreversible heart failure [48-52],... 

Gerull, B., Gramlich, M., and Atherton, J. (2002). Mutations of TTN, encoding the giant muscle filament titin, cause familial dilated cardiomyopathy. Nat. Genet. 30, 201-204. 

Hereditary haemochromatosis Usuahy with family history of cirrhosis, skin hyperpigmentation, diabetes melhtus, pseudo-gout and/or cardiomyopathy, all due to iron overload. 

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