Hypertrophic cardiomyopathy (HCM, OMIM#192600) is a well-known primary disease of the myocardium. HCM is defined by unexplained ventricular hypertrophy with preferential hypertrophy of the septum and anterior left ventricular wall in the absence of a detectable cause.
This disorder has a prevalence within the general population of one in 500, or 0.2%. It follows a heterogeneous autosomal dominant inheritance pattern and often develops during childhood and adolescence. Individuals with the disease may develop myocardial ischemia, arrhythmia or heart failure. Notably, HCM is the most common cause of sudden cardiac death in young adults and athletes.
Genes encoding for cardiac sarcome proteins accounts for up to 60% of cases of HCM. The remaining causes include other genetic syndromes (mostly inherited metabolic and neuromuscular disorders) and non-genetic factors mimicking the genetic form of the disease .
Genes involved in HCM and corresponding estimated proportion of mutations causing HCM:
This test is indicated for:
- Diagnosis confirmation and refinement of a patient with a definite or suspected cardiomyopathy
- Predictive diagnosis in asymptomatic relatives 
- Individuals with a suspected or confirmed diagnosis of HCM
- Individuals with a family history of sudden death
- Individuals with left ventricular thickening and suspected HCM
- Athletes with ventricular hypertrophy
- Genetic study of family members for abnormalities identified in index cases
Test Benefits & Risk Management
Benefits of this test are:
- The diagnosis confirmation and refinement of a patient supposedly affected by HCM, e.g. discrimination between HCM and other causes of left ventricular (LV) hypertrophy, including hypertension, “athlete’s heart” and other metabolic or infiltrative storage disorders with LV hypertrophy that can mimic clinically diagnosed HCM (Fabry disease, Noonan disease, Danon disease, etc.).
An early identification, would allow an earlier treatment of these different conditions.
- The subsequent identification of affected relatives in families where a causative HCM mutation has already been found. This would allow an earlier management of at-risk members and avoid unnecessary further screening of non-carriers.
Risk management includes, but is not limited to:
- Monitoring of the disease: Regular cardiologic evaluation is advised to detect clinical signs of HCM and to estimate the risk of sudden cardiac death .
- Lifestyle changes: Intense physical activity (e.g., burst activities, sprinting), or systematic isometric exercise (e.g., heavy lifting) will be discouraged .
- Implantable cardiac defibrillators (ICDs) for secondary or primary prevention in patients at right risk of sudden cardiac death .
- A range of drugs exists to manage specific symptoms. For instance, drugs appropriate to control heart failure symptoms, such as beta-blockers, which may be used to relieve palpitation and calcium antagonists, which can similarly reduce palpitations and chest pains .
- Surgical septal myectomy , which removes some of the thickened muscle from the septum thereby relieving obstruction or alcohol septal ablation  for progressive and drug-refractory heart failure caused by left ventricular outflow tract (LVOT) obstruction.
- Heart transplantation for systolic (or less frequently intractable diastolic) dysfunction associated with severe unrelenting symptoms .
- Drug therapy (Disopyramide, amiodarone, dronedarone) [2,5] or possibly radiofrequency ablation or surgical maze procedure for atrial fibrillation .
This panel includes the 8 genes encoding for main cardiac sarcomere protein. It also comprises 3 genes responsible for most common HCM genocopies (HCM phenotype not due to mutations in sarcomeric genes), therefore also allowing for differential diagnosis.
It is estimated that > 80% of mutations currently reported for HCM are covered with this panel.
|Gene||MIM Gene||Related Disorder|
|ACTC1||102540||HCM, DCM, LVNC|
|MYBPC3||600958||HCM, DCM, LVNC|
|MYH7||160760||HCM, DCM, LVNC|
|PRKAG2||602743||Glycogen storage disease of heart, lethal congenital, HCM|
|PTPN11||176876||Noonan syndrome, Leopard syndrome|
|TNNI3||191044||HCM, DCM, LVNC, RCM|
|TNNT2||191045||HCM, DCM, LVNC, RCM|
|TPM1||191010||HCM, DCM, LVNC|
- Targeted capture of all coding exons and exon-intron boundaries followed by NGS.
- Sanger sequencing on low coverage regions and all relevant variants
Two months on average
- Elliott PM, Anastasakis A, Borger MA, et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: The Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J. 2014 Aug 29. PubMed PMID: 25173338.
- Gersh BJ, Maron BJ, Bonow RO et al. 2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011; 124: e783-e831. PubMed PMID: 22075469.
- Pelliccia A, Fagard R, Bjornstad HH, et al. Recommendations for competitive sports participation in athletes with cardiovascular disease: a consensus document from the Study Group of Sports Cardiology of the Working Group of Cardiac Rehabilitation and Exercise Physiology and the Working Group of Myocardial and Pericardial Diseases of the European Society of Cardiology. Eur Heart J. 2005; 26:1422– 45. PubMed PMID: 15923204.
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- Harris KM, Spirito P, Maron MS, et al. Prevalence, clinical profile, and significance of left ventricular remodeling in the end-stage phase of hypertrophic cardiomyopathy. Circulation. 2006; 114:216 –25. PubMed PMID: 16831987.
Gaita F, Di Donna P, Olivotto I, et al. Usefulness and safety of transcatheter ablation of atrial fibrillation in patients with hypertrophic cardiomyopathy. Am J Cardiol. 2007; 99:1575– 81. PubMed PMID: 17531584.