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| {{EH}} | | {{EH}} |
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| While most literature so far focuses on European, American, and Japanese populations, HCM appears in all racial groups. The incidence of HCM is about 0.2% to 0.5% of the general population.
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| ==Genetics==
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| HCM is the most common genetically transmitted cardiovascular disease. Penetrance of HCM is incomplete and age-related. The disease may be sporadic but affected family members are discovered in 13% of cases. More than 70 mutations involving at least 7 chromosomes encoding structural proteins of the myocyte have been discovered. These mutations have varying degrees of penetrance and even the same mutation may have variable expression, implying superimposed effects of other genes or environmental influences.
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| Hypertrophic cardiomyopathy is inherited as an [[autosomal dominant]] trait and is attributed to mutations in one of a number of genes that encode for one of the [[sarcomere]] [[protein]]s including beta-cardiac myosin heavy chain (the first gene identified), cardiac actin, [[troponin T|cardiac troponin T]], alpha-tropomyosin, [[troponin I|cardiac troponin I]], cardiac myosin-binding protein C, and the myosin light chains. Currently there are more than 400 mutations in these genes. The prognosis is variable, based on the gene mutation. In individuals without a family history of HCM, the most common cause of the disease is a [[mutation|de novo mutation]] of the gene that produces the β-myosin heavy chain.
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| An insertion/deletion polymorphism in the [[gene]] encoding for [[angiotensin converting enzyme]] (ACE) alters the clinical [[phenotype]] of the disease. The D/D (deletion/deletion) genotype of ACE is associated with more marked hypertrophy of the left ventricle and may be associated with higher risk of adverse outcomes
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| <ref name="Doolan, Nguyen et al 2004">Doolan G, Nguyen L, Chung J, Ingles J, Semsarian C. Progression of left ventricular hypertrophy and the angiotensin-converting enzyme gene polymorphism in hypertrophic cardiomyopathy. ''Int J Cardiol''. 2004 Aug; '''96'''(2):157–63. ([http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15314809 Medline abstract])</ref> <ref name="Marian, Yu et al 1993">Marian AJ, Yu QT, Workman R, Greve G, Roberts R. Angiotensin-converting enzyme polymorphism in hypertrophic cardiomyopathy and sudden cardiac death. ''Lancet''. 1993 Oct 30; '''342'''(8879):1085–6. ([http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8105312 Medline abstract])</ref>.
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| ===Specific Chromosomal Abnormalities===
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| ====β [[Myosin]] Heavy Chain-Chromosome 14 q11.2-3====
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| Accounts for approximately 35%-45% of cases. Significant [[LVH]] ([[left ventricular hypertrophy]]) is usually noted. The Arg403Gln mutation is associated with an extremely poor prognosis with average age of death at 33 years, while the Val606Met mutation is associated with a better prognosis.
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| ====Cardiac Myosin Binding Protein-C-Chromosome 11====
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| Accounts for another 15%-35% but has a reduced penetrance so may actually be more. Patients generally present later in life and in general, have a better prognosis than with the prior 2 mutations. Up to 60% at age 50 years have no [[LVH]].
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| ====Cardiac Troponin T-Chromosome 11====
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| Accounts for approximately 15% of cases. Substantially less hypertrophy is noted but histology demonstrates the characteristic myocyte disarray of HCM. Most mutations of this gene are associated with markedly reduced survival.
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| ====Other Genetic Abnormalities====
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| Other genes encoding alpha tropomyosin, myosin regulatory light chain, cardiac [[troponin I]] and cardiac [[troponin C]] have been implicated. A mutation on Chromosome 7 is associated with HCM and the [[WPW]] ([[Wolff-Parkinson-White syndrome]]).
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| ==References== | | ==References== |