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(Circulation. 2008;117:1775-1777.)
© 2008 American Heart Association, Inc.

Editorial

Disease-Modifying Mutations in Familial Hypertrophic Cardiomyopathy

Complexity From Simplicity

Denise Hilfiker-Kleiner, PhD; Ralph Knöll, MD

From the Department of Cardiology & Angiology Hannover Medical School, Hannover, Germany (D.H.-K.) and the Heart Centre Göttingen, Georg August University, Goettingen, Germany (R.K.).

Correspondence to Denise Hilfiker-Kleiner, PhD, Abt. Kardiologie und Angiologie, Medizinische Hochschule Hannover Carl-Neuberg Str. 1, 30625 Hannover, Germany. E-mail hilfiker.denise@mh-hannover.de

Key Words: Editorials • cardiomyopathy • genetics

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Cardiomyopathies are primary disorders of cardiac muscle associated with abnormalities of cardiac wall thickness, chamber size, contraction, relaxation, conduction, and rhythm. They are a major cause of morbidity and mortality at all ages and, like acquired forms of cardiovascular disease, frequently progress into heart failure.¹ In contrast to dilated cardiomyopathy (DCM), which is characterized by left or biventricular dilation in association with depressed myocardial contractility,¹ familial hypertrophic cardiomyopathy (FHC) is characterized by increased cardiac mass with myocyte and myofibrillar disarray. The disease is associated with electrical instability (ie, atrial and ventricular arrhythmias), which makes it the leading cause of death in young athletes. There is marked diversity in the morphological features and clinical manifestations of both DCM and FHC.²

Article p 1820

Family studies have demonstrated that hypertrophic cardiomyopathy is a heritable disorder that is transmitted as an autosomal-dominant trait or as a sporadic disease. There is neither a racial nor an ethnic predisposition to this condition. Hypertrophic cardiomyopathy is not a rare condition; several noninvasive studies have demonstrated echocardiographic criteria for this disease in 0.2% of young adults (reviewed by Maron³).

Genetic linkage studies in FHC have found disease loci on at least 14 different genes, most of them encoding sarcomeric genes; hence, FHC has been called a disease of the sarcomere. In addition, several mutations within the Ras pathway have been shown to cause at least syndromic forms of hypertrophic cardiomyopathy,^4,5 pointing to the presence of additional but poorly understood disease-causing and/or modifier genes.

Thus far, however, . . . [Full Text of this Article]