Hypertrophic cardiomyopathy is a disease of the myocardium (the muscle of the heart) in which a portion of the myocardium ishypertrophied (thickened) without any obvious cause. It is perhaps most well known as a leading cause of sudden cardiac death in young athletes.[The occurrence of hypertrophic cardiomyopathy is a significant cause of sudden unexpected cardiac death in any age group and as a cause of disabling cardiac symptoms. Younger people are likely to have a more severe form of hypertrophic cardiomyopathy
HCM is frequently asymptomatic until sudden cardiac death, and for this reason some suggest routinely screening certain populations for this disease.
While most literature so far focuses on European, American, and Japanese populations, HCM appears in all racial groups. The prevalence of HCM is about 0.2% to 0.5% of the general population.
Myosin heavy chain mutations are associated with development of familial hypertrophic cardiomyopathy.
Signs and symptoms
The clinical course of HCM is variable. Many patients are asymptomatic or mildly symptomatic. The symptoms of HCM include dyspnea (shortness of breath), chest pain (sometimes known as angina), uncomfortable awareness of the heart beat (palpitations), lightheadedness, fatigue, fainting (called syncope) and sudden cardiac death.Dyspnea is largely due to increased stiffness of the left ventricle, which impairs filling of the ventricles and leads to elevated pressure in the left ventricle and left atrium. Symptoms are not closely related to the presence or severity of an outflow tract gradient. Often, symptoms mimic those of congestive heart failure (esp. activity intolerance & dyspnea), but treatment is very different. To treat with diuretics (a mainstay of CHF treatment) will exacerbate symptoms in hypertrophic cardiomyopathy by decreasing ventricular volume and increasing outflow resistance.
Genetics
| Gene | Locus | Type |
|---|---|---|
| MYH7 | 14q12 | CMH1 (192600) |
| TNNT2 | 1q32 | CMH2 (115195) |
| TPM1 | 15q22.1 | CMH3 (115196) |
| MYBPC3 | 11p11.2 | CMH4 (115197) |
| ? | ? | CMH5 |
| PRKAG2 | 7q36 | CMH6 (600858) |
| TNNI3 | 19q13.4 | CMH7 |
| MYL3 | 3p | CMH8 (608751) |
| TTN | 2q24.3 | CMH9 |
| MYL2 | 12q23-q24 | CMH10 |
| ACTC1 | 15q14 | CMH11 (612098) |
| CSRP3 | 11p15.1 | CMH12 (612124) |
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 proteins.
About 50-60% of patients with a high index of clinical suspicion for HCM will have a mutation identified in at least 1 of 9 sarcomeric genes. Approximately 45% of these mutations occur in the β myosin heavy chain gene on chromosome 14 q11.2-3, while approximately 35% involve the cardiac myosin binding protein C gene. Since HCM is typically an autosomal dominant trait, children of an HCM parent have 50% chance of inheriting the disease-causing mutation. Whenever a mutation is identified through genetic testing, family-specific genetic testing can be used to identify relatives at-risk for the disease (HCM Genetic Testing Overview). In individuals without a family history of HCM, the most common cause of the disease is a de novo mutation of the gene that produces the β-myosin heavy chain.
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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