Hypertrophic cardiomyopathy is the most common genetic cardiomyopathy with a prevalence of 1 in 500 in the general population. It is diagnosed phenotypically by abnormal thickening of the ventricular walls in the absence of abnormal loading conditions and the current criteria dictates that there is a wall thickness of greater than 15 mm in at least one LV myocardial segment, however in some cases 13mm of hypertrophy is sufficient for diagnosis. Patients with the disease often show symptoms including but not limited to arrythmia, chest pain, fatigue, fluttering or pounding feeling in the chest, and lightheadedness. Management of HCM is focused on symptom relief and reducing possible causes of heart failure.
| Name | Type | HCM Type | HCM Frequency | Chromosome | Protein | Function | Think or Thick Myofilament Protein |
|---|---|---|---|---|---|---|---|
| MYH7 | Myosin | - | 30-35% | 14 | β-myosin heavy chain | instructs on how to make β-myosin heavy chain | thick |
| MYL3 | Myosin | 8 | <1% | 3 | Myosin light chain | Myosin heavy chain 7 binding protein | thick |
| MYL2 | Myosin | 12 | <1% | 12 | Regulatory myosin light chain | Myosin heavy chain 7 binding protein | thick |
| MYH6 | Myosin | 14 | <0.5% | 14 | Myosin heavy chain alpha | Sarcomere protein expressed at low levels in the adult human heart | - |
| MYBPC3 | Myosin | 4 | 20-30% | 11 | Myosin binding protein-C3 | Cardiac Contraction | thick |
| TNNC1 | Troponin | 13 | <1% | 3 | Cardiac Troponin C | Calcium sensitive regulator of myofilament function | thin |
| TNNI3 | Troponin | 7 | <5% | 19 | Cardiac troponin I | Inhibitor of acto-myosin interaction | thin |
| TNNT2 | Troponin | 2 | 10-15% | 1 | Cardiac troponin T | Regulator of acto-myosin interaction | thin |
| ACTC1 | Actin | 11 | <0.5% | 15 | Cardiac α - actin | Acto-myosin interaction | thin |
| NEXN | Actin | 20 | - | 1 | Nexilin | Z disc protein | - |
| TPM1 | Actin | 3 | <5% | 15 | Α-tropomyosin 1 chain | Places the troponin complex on cardiac actin | thin |
| Name | Symptoms |
|---|---|
| TPMI | hypertrophic cardiomyopathy, mild degree of hypertrophy with a high incidence of sudden death, ventricular myosite disarray |
| ACTC1 | Hypertrophic cardiomyopathy, septal bulge of left ventricular outflow tract, Wolff-Parkinson-White arrhythmia (rare), early onset in some patients, highly penetrant but low morbidity |
| NEXN | Left ventricular hypertrophy, septal hypertrophy asymmetric interventricular, left ventricular anterior wall hypertrophy (in some patients), atrial fibrillation (in some patients) |
| Name | Symptoms |
|---|---|
| MYBPC3 | Hypertrophic cardiomyopathy, Chest pain, Cardiomegaly, Bilateral ventricular hypertrophy, Enlarged right atrium, Progressive heart failure, Pericardial effusion, First-degree atrioventricular block, Reduced left ventricular systolic function, Reduced shortening fraction of left ventricle, Reduced right ventricular systolic function, Enlarged left ventricular end systolic diameter, Thickened interventricular septum, Complete and incomplete left bundle branch block, Right bundle branch block, Ventricular fibrillation, Cardiac arrest, sudden dieath may occur during vigorous exercise, stroke |
| MYL3 | Palpitations, systolic ejection murmur, hypertrophic left ventricular free wall, hypertrophic ventricular septum (primarily apical half), massive hypertrophy of cardiac papillary muscles, massive thickening of the mid-left ventricular chamber walls, anterior displacement of mitral valve (closer to ventricular septum), significant pressure gradient between proximal and distal left ventricular cavities, biatrial enlargement (in some patients), restrictive physiology (in some patients), left ventricular hypertrophy pattern seen on electrocardiogram (ECG), left atrial enlargement seen on ECG, T-wave inversion of mild amplitude seen on ECG, ventricular fibrillation, elevated left ventricular end-diastolic pressure, cardiac arrest, sudden cardiac death, extensive myocyte disorganization seen on biopsy, myocyte hypertrophy, interstitial fibrosis, early-onset severe disease in homozylogous patients |
| MYL2 | Chest pain, palpitations, thickening of left ventricular wall, mild to moderate septal hypertrophy, asymmetric septal hypertrophy, hypertrophy involving both ventricular septum and left ventricular free wall, systolic anterior motion of mitral valve (in some patients), massive hypertrophy of cardiac papillary muscles (in some patients), massive thickening of the mid-left ventricular chamber walls (in some patients), significant pressure gradient between proximal and distal left ventricular cavities (in some patients), left ventricular hypertrophy pattern seen on electrocardiogram (ECG), prolonged Q waves seen on ECG, Q waves more than one-third ensuing R wave in depth seen on ECG, repolarization abnormalities with marked T-wave inversion seen on ECG, supraventricular tachycardia (in some patients), ventricular fibrillation (in some patients), sudden cardiac death (in some patients), Premature fatigue on exertion, reduced penetrance is present in some families, early onset in some patients, some affected individuals may be asymptomatic, marked variability in severity of phenotype |
| MYH6 | Increased left ventricular wall thickness, decreased left ventricular fractional shortening, decreased left ventricular ejection fraction, ventricular outflow obstruction, progression to cardiac dilation, refractory heart failure, variable age of onset from third to eighth decade of life |
| Name | Symptoms |
|---|---|
| TNNT2 | Symptoms unclear |
| TNNI3 | Ventricular hypertrophy, apical hypertrophy (in some patients), ventricular preexcitation, Wolff-Parkinson-White, atrial fibrillation (in some patients), sudden cardiac death in some families |
| TNNC1 | Dyspnea on exertion, syncope, with or without exertion, chest pain, left anterior hemiblock (in some patients), right bundle branch block (in some patients), atrial fibrillation (in some patients), ventricular fibrillation (may be associated with physical or emotional stress), increased left ventricular wall thickness, concentric hypertrophy of left ventricle (in some patients), asymmetric septal wall hypertrophy (in some patients), left ventricular outflow obstruction, significant voltage criteria for biventricular hypertrophy seen on ECG, ST segment depression in anterior leads seen on ECG, Variable age of onset from first to sixth decade of life |
| Name | Symptoms |
|---|---|
| 2 | 1.3 - 3 cm |
| 3 | hypertrophic cardiomyopathy, mild degree of hypertrophy with a high incidence of sudden death, ventricular myosite disarray |
| 4 | Hypertrophic cardiomyopathy, Chest pain, Cardiomegaly, Bilateral ventricular hypertrophy, Enlarged right atrium, Progressive heart failure, Pericardial effusion, First-degree atrioventricular block, Reduced left ventricular systolic function, Reduced shortening fraction of left ventricle, Reduced right ventricular systolic function, Enlarged left ventricular end systolic diameter, Thickened interventricular septum, Complete and incomplete left bundle branch block, Right bundle branch block, Ventricular fibrillation, Cardiac arrest, sudden dieath may occur during vigorous exercise, stroke |
| 7 | Ventricular hypertrophy, apical hypertrophy (in some patients), ventricular preexcitation, Wolff-Parkinson-White, atrial fibrillation (in some patients), sudden cardiac death in some families |
| 8 | Palpitations, systolic ejection murmur, hypertrophic left ventricular free wall, hypertrophic ventricular septum (primarily apical half), massive hypertrophy of cardiac papillary muscles, massive thickening of the mid-left ventricular chamber walls, anterior displacement of mitral valve (closer to ventricular septum), significant pressure gradient between proximal and distal left ventricular cavities, biatrial enlargement (in some patients), restrictive physiology (in some patients), left ventricular hypertrophy pattern seen on electrocardiogram (ECG), left atrial enlargement seen on ECG, T-wave inversion of mild amplitude seen on ECG, ventricular fibrillation, elevated left ventricular end-diastolic pressure, cardiac arrest, sudden cardiac death, extensive myocyte disorganization seen on biopsy, myocyte hypertrophy, interstitial fibrosis, early-onset severe disease in homozylogous patients, |
| 10 | Chest pain, palpitations, thickening of left ventricular wall, mild to moderate septal hypertrophy, asymmetric septal hypertrophy, hypertrophy involving both ventricular septum and left ventricular free wall, systolic anterior motion of mitral valve (in some patients), massive hypertrophy of cardiac papillary muscles (in some patients), massive thickening of the mid-left ventricular chamber walls (in some patients), significant pressure gradient between proximal and distal left ventricular cavities (in some patients), left ventricular hypertrophy pattern seen on electrocardiogram (ECG), prolonged Q waves seen on ECG, Q waves more than one-third ensuing R wave in depth seen on ECG, repolarization abnormalities with marked T-wave inversion seen on ECG, supraventricular tachycardia (in some patients), ventricular fibrillation (in some patients), sudden cardiac death (in some patients), - Premature fatigue on exertion - Reduced penetrance is present in some families - Early onset in some patients - Some affected individuals may be asymptomatic - Marked variability in severity of phenotype |
| 11 | Hypertrophic cardiomyopathy - Septal bulge of left ventricular outflow tract - Wolff-Parkinson-White arrhythmia (rare)- Early onset in some patients - Highly penetrant, but low morbidity |
| 13 | Dyspnea on exertion - Syncope, with or without exertion, Chest pain, Left anterior hemiblock (in some patients), Right bundle branch block (in some patients), Atrial fibrillation (in some patients), Ventricular fibrillation (may be associated with physical or emotional stress), Increased left ventricular wall thickness, Concentric hypertrophy of left ventricle (in some patients), Asymmetric septal wall hypertrophy (in some patients), Left ventricular outflow obstruction, Significant voltage criteria for biventricular hypertrophy seen on ECG, ST segment depression in anterior leads seen on ECG, Variable age of onset from first to sixth decade of life |
| 14 | Increased left ventricular wall thickness, Decreased left ventricular fractional shortening, Decreased left ventricular ejection fraction, Ventricular outflow obstruction, Progression to cardiac dilation, Refractory heart failure- Variable age of onset from third to eighth decade of life |
| 20 | Left ventricular hypertrophy, Septal hypertrophy, asymmetric interventricular, Left ventricular anterior wall hypertrophy (in some patients), Atrial fibrillation (in some patients) |