Development of left ventricular hypertrophy in adults with hypertrophic cardiomyopathy caused by cardiac myosin-binding protein C gene mutations
Barry J. Maron, MD, FACC*,
Hideshi Niimura, MD ,
Susan A. Casey, RN ,
Marjorie K. Soper, MD,
Gregory B. Wright, MD, FACC,
J. G. Seidman, PhD and
Christine E. Seidman, MD
* Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, Minneapolis, Minnesota, USA
First Department of Internal Medicine, Kagoshima University, Kagoshima, Japan
Children’s Heart Clinic, Minneapolis, Minnesota, USA
Howard Hughes Medical Institute and Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA
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Figure 1 This myosin-binding protein C (MyBPC) pedigree shows generational skipping of the hypertrophic cardiomyopathy (HCM) phenotype. Note that the adult woman (II.2) without left ventricular hypertrophy (LVH) on the echocardiogram (the 12-lead electrocardiogram was also normal) was, nevertheless, the offspring of a father with LVH and the HCM mutant gene (I.2) and also passed the HCM gene to a son with LVH (III.4); a genetically affected sister also has HCM with LVH (II.3). Circles = females; squares = males; solid symbols = genetically affected relatives with LVH (representing HCM phenotype); open symbols = genetically affected relatives without LVH; stippled symbols = family members in whom clinical and genetic status was undetermined. The presence (+) or absence (–) of the MyBPC mutation is indicated for persons in whom deoxyribonucleic acid was tested for the mutation segregating in their family.
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Figure 2 Development of hypertrophic cardiomyopathy (HCM) phenotype in adulthood. Stop-frame two-dimensional echocardiograms at end- diastole, at the papillary muscle level in the parasternal short-axis plane, from a woman with familial HCM at age 27 years, when genotyping was initiated (A), and at age 33 years, after myosin-binding protein C mutation was known (B). (A) Left ventricular (LV) thickness is normal ( 12 mm) in all segments of the wall, including the ventricular septum (VS). (B) Six years later, at age 33, wall thickness was abnormally increased (19 to 20 mm) in the anterior ventricular septum (AVS) and posterior septum (PVS), as well as the anterolateral free wall (AFW). Mild mitral valve systolic anterior motion (without septal contact or outflow gradient) appeared at this time, although it is not shown here. Calibration marks are 10 mm apart.
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Figure 3 Development of hypertrophic cardiomyopathy (HCM) phenotype in adulthood. Echocardiograms from a man with familial HCM at age 29 years, when genotyping was initiated (A,C), and at age 35 years, after the MyBPC mutation was known (B). (A) Parasternal long-axis view at end-diastole, showing normal thickness of the ventricular septum (VS) (i.e., 11 mm) and elongated mitral valve (MV) leaflets. (B) Six years after the initial echocardiogram, the long-axis view at end-diastole shows, in addition to greatly elongated MV leaflets, hypertrophy of the anterior basal septum (arrows), which bulges prominently into the left ventricular (LV) outflow tract. (C) Apical four-chamber view from the initial echocardiogram with normal LV wall thickness, showing only a moderate degree of systolic anterior motion (arrow) produced preferentially by the distal portion of the posterior mitral leaflet (as the sole and initial clinical evidence of HCM); the anterior mitral leaflet (AmL) coapts abnormally at the base of the posterior leaflet, rather than at its tip. Calibration marks are 10 mm apart. Ao = aorta; LA = left atrium; RV = right ventricle.
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