Table 2. Major genes associated with dilated cardiomyopathy.
| Gene | Protein | Estimated prevalence in DCM (%) | Age of onset of DCM (years) | Notes |
|---|---|---|---|---|
| TTN | Titin | 12–25% | DCM: Usually 40–59 | - Usually, isolated DCM |
| - More common in women than in men; variable prognosis but family clustering | ||||
| LMNA | Lamin A/C | 5–10% (up to 30 if conduction disease also present) | 30–49 and penetrance is almost complete at the age of 70; conduction disease usually prominent | - Subset of Emery–Dreifuss muscular dystrophy |
| Nuclear membrane | - Phenotypic expression is characterized by a relatively high incidence of sudden cardiac death or major ventricular arrhythmias, even before the development of systolic left ventricular dysfunction | |||
| - Class IIa for ICD implantation: NSVT during monitoring, EF <45% at first evaluation, male and non-missense mutations96),97) | ||||
| MYH7 | β-Myosin heavy chain | 4–10% | Variable: adolescence to 49 | - Primarily HCM; also, LVNC and RCM |
| Sarcomere | - Prognosis variable depending on site of genetic variant; homogeneity within families | |||
| MYH6 | α-Myosin heavy chain | 4% | Variable: adolescence to 49 | - Primarily HCM |
| Sarcomere | - Prognosis variable depending on site of genetic variant; homogeneity within families | |||
| MYPN | Myopalladin | 3–4% | Variable: adolescence to 59 | - Usually, isolated DCM |
| Sarcomere, Z-disc | - Variable presentation with some early deaths due to heart failure | |||
| DSP | Desmoplakin | 3–4% | Variable: mostly 40–49 | - ARVC |
| Desmosome | - Identified in multiple patients with advanced DCM although natural history uncertain; arrhythmic burden seems to be much lower than in ARVC | |||
| RBM20 | RNA-binding protein 20 | 1–5% | Adolescence to 50; can present with SCD or advanced heart failure | - Usually, isolated DCM |
| Spliceosome | - Rapid progression: SCD and end-stage heart failure are common, with a high incidence of ventricular arrhythmias | |||
| - Severe disease expression in male patients98) | ||||
| TNNT2 | Cardiac muscle troponin T | 2–3% | Variable: adolescence to 49 | - HCM, LVNC, and RCM |
| Sarcomere | - Prognosis variable depending on site of genetic variant; homogeneity within families | |||
| SCN5A | SCN5A (sodium channel protein type 5, α subunit) | 2–3% | Adolescence | - Brugada syndrome and LQTS |
| Ion channel | - Early onset, commonly with atrial fibrillation; not associated with risk of ventricular arrhythmias | |||
| TPM1 | α-Tropomyosin | 0.5–1.0% | Variable: adolescence to 49 | - Other cardiomyopathy: HCM, LVNC, and RCM |
| Sarcomere | - Prognosis variable depending on site of genetic variant; homogeneity within families |
ARVC = arrhythmogenic right ventricular cardiomyopathy; DCM = dilated cardiomyopathy; EF = ejection fraction; HCM = hypertrophic cardiomyopathy; ICD = implantable cardioverter defibrillator; LQTS = long QT syndrome; LVNC = left ventricular noncompaction; NSVT = nonsustained ventricular tachycardia; RCM = restrictive cardiomyopathy; SCD = sudden cardiac death.