Hypertrophic cardiomyopathy

• attributed to multiple gene mutations that affect several proteins of the sarcomere.
  • abnormal heavy-chain myosin proteins (most common)
  • tropomyosin (mild hypertrophy, but high risk of sudden death)
  • troponins
  • actin
• autosomal dominant (most common), with spontaneous mutations and variable degrees of gene mutation expression possible.

Pathophysiology

• Classic hypertrophic cardiomyopathy is associated with asymmetric hypertrophy of the interventricular septum (ASH, asymmetric septal hypertrophy) that is greater than the left ventricular free wall hypertrophy.
• Dynamic obstruction of the left ventricular outflow tract, so-called idiopathic subaortic stenosis (IHSS, idiopathic hypertrophic subaortic stenosis), is seen in many patients.
• However, generalized hypertrophy also may be seen.
• Although severe hypertrophy of the left ventricular free wall and the septum may be associated with an increased risk of sudden death, some forms of hypertrophic cardiomyopathy may have a high risk of sudden death in the presence of relatively mild hypertrophy (eg, the known mutations on the tropomyosin gene).

Screening

• The dominant inheritance of many forms of hypertrophic cardiomyopathy is the rationale for screening examinations of family members of patients who are diagnosed with these disorders.
•  Furthermore, a positive family history of sudden death at a young age from hypertrophic cardiomyopathy, such as described for the boy in the vignette, is a significant risk factor for premature or sudden cardiac death in patients who have hypertrophic cardiomyopathy.
• Echocardiography is the most commonly employed screening tool for individuals who have such a positive history. Pitfalls in echocardiographic screening include the possibility of a significant hypertrophy developing after a "normal" echocardiogram or the possibility of the screened individual having a form of hypertrophic cardiomyopathy that has milder degrees of hypertrophy but a poorer prognosis (tropomyosin mutations).
• Genetic screening of an individual to determine whether he or she has hypertrophic cardiomyopathy or to determine which type of cardiomyopathy an affected individual has remains problematic. Clinical genetic testing is unavailable at this time.
• Blood samples collected from families in whom there are multiple affected individuals can be used to find new mutations or to confirm that a specific family has a known mutation. However, it is not currently practical to attempt to use a genetic screen for a single patient who is not known to have hypertrophic cardiomyopathy.
• Electrocardiography results may be very abnormal in adolescents or children who have hypertrophic cardiomyopathy, but electrocardiographic findings may be normal until echocardiography results are abnormal for a longer period of time.
• Exercise myocardial perfusion scanning may have a role in risk stratification for patients who have hypertrophic cardiomyopathy because exercise-related myocardial ischemia appears to be one of the mechanisms for syncope, chest pain, and sudden death in affected patients. However, perfusion scanning cannot be used to screen for the presence of hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy appears in 40% of patients with Friedrich Ataxia

References:
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children, and adolescents. Pediatr Clin North Am. 1999;46:221-234
Maron BJ, Moller JH, Seidman CE, et al. Impact of laboratory molecular
diagnosis on contemporary diagnostic criteria for genetically
transmitted cardiovascular diseases: hypertrophic cardiomyopathy,
long-QT syndrome, and Marfan syndrome. A statement for healthcare
professionals from the Councils on Clinical Cardiology, Cardiovascular
Disease in the Young, and Basic Science, American Heart Association.
Circulation. 1998;98:1460-1471
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Cardiol Rep. 2000;2:134-140
Towbin JA. Pediatric myocardial disease. Pediatr Clin North Am. 1999;46:289-312