Aj. Marian et R. Roberts, FAMILIAL HYPERTROPHIC CARDIOMYOPATHY - A PARADIGM OF THE CARDIAC HYPERTROPHIC RESPONSE TO INJURY, Annals of medicine, 30, 1998, pp. 24-32
Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease cau
sed by mutations in sarcomeric proteins. It is characterized by left v
entricular hypertrophy in the absence of an increased external load, a
nd myofibrillar disarray. While hypertrophy is a common cardiac respon
se to injury, disarray is the pathological hallmark of HCM. A large nu
mber of mutations in genes coding for sarcomeric proteins, ie the beta
-myosin heavy chain (beta-MyHC), cardiac troponin (cTn)T, cTnI, alpha-
tropomyosin, myosin-binding protein C (MyBP-C), and essential and regu
latory myosin light chains in patients with HCM have been identified,
Genotype-phenotype correlation studies have shown that mutations carry
prognostic significance. Unlike mutations in the beta-MyHC gene, the
prognostic significance of which reflect their hypertrophic expressivi
ty, cTnT mutations are associated with a mild degree of hypertrophy, b
ut a high incidence of sudden cardiac death. Mutations in MyBP-C are a
ssociated with mild hypertrophy, and a benign prognosis. However, the
genetic background in which the mutations occur, and possibly environm
ental factors also, modulate phenotypic expression of HCM. Functional
studies of mutations causing HCM have shed significant light into the
pathogenesis of HCM and have led to the hypothesis that mutant sarcome
ric proteins function as 'poison peptides' exerting a dominant-negativ
e effect on the function of the cardiac myocytes, followed by structur
al changes and a compensatory hypertrophy.