Hypertrophic cardiomyopathy (HCM) is found through¬out the world with a prevalence in North America of 0.2%. Before the diagnosis of HCM is considered hyper¬tensive heart disease, a major cause of the left ventricle hypertrophy, and other causes of hypertrophy must be excluded. In practice HCM is defined and diagnosed by the demonstration of unexplained left ventricular hypertrophy.
Hypertrophic cardiomyopathy is a disease caused by a wide variety of mutations in genes encoding cardiac sarcomeric proteins, which leads to inappropriate and often severe hypertrophy of the myocardium.
A. Genetics
Approximately 60% of cases are familial and are inherited in a Mendelian single gene autosomal dominant fashion. More than 150 mutations in 10 culprit genes that encode sarcomeric proteins are implicated in this disease. The most common of these culprit genes include:
1. Beta myosin heavy chain (MYH7), approximately 35%
2. Cardiac troponin-2 (TNNT2), approximately 15%
3. Myosin binding protein C genes, approximately 15%
4. Alpha tropomyosin
5. Essential myosin light chain
6. Troponins-I
7. Alpha cardiac actin
8. Regulatory myosin light chain.
Familial HCM can be caused by genetic defects at more than one locus, therefore, it is a genetically heterogeneous disease. The mutations of the troponins-T and some mutations of the beta myosin heavy chain appear to be associated with sudden death more often than other mutations. Some mutations may be associated with a high incidence of sudden cardiac death, whereas others appear to have a more benign course. This has led to the hypo¬thesis that genotyping may facilitate the identification of individuals at risk for sudden death. But there is extreme variability and even mutations that were considered by some to be malignant, MYH7 and TNNT2, often run a benign course. In a study by Ackerman et al. so-called ‘‘malignant’’ mutation was found in only 1% of 293 study patients. The authors concluded that given the low prevalence of malignant MYH7 and TNNT2 mutations in a large study, genetic testing was unlikely to contribute significantly to risk assessment.

Страницы: 1 | 2 | 3 | 4 | 5