Table 2.
Clinical manifestations, mutated genes, and classical heart defects with their relative prevalence among RASopathies and relative prevalence of hypertrophic cardiomyopathy
| Gene | Clinical Features | HCM |
|---|---|---|
| Noonan syndrome | ||
| PTPN11 | PVS (65%), atrioventricular septal defects (18%), ASD (10%), VSD (9%), PDA (6%), mitral valve abnormalities (2.5%), Tetralogy of Fallot (<1%), aortic coarctation (<1%) | HCM (20%) |
| SOS1 | PVS (70%), ASD (14.5%), mitral valve abnormalities (4%) | HCM (18%) |
| RAF1 | PVS (21%), ASD (20%), mitral valve abnormalities (13%), Tetralogy of Fallot (2.8%), aortic coarctation (1.8%) | HCM (65%) |
| RIT1 | PVS (74%), ASD (30%), PDA (7%), mitral valve abnormalities (13%), biventricular obstruction (<1%) | HCM (36%) |
| SHOC2 | PVS (32%), ASD (32%), mitral valve abnormalities (27%), VSD (13%) | HCM (30%) |
| NRAS | PVS (14%) | HCM (39%) |
| CBL | PVS (50%), ASD (10%), mitral valve abnormalities (10%) | HCM (10%) |
| Noonan syndrome with multiple lentigines | ||
| PTPN11 | Biventricular hypertrophy (46%), LVOTO (40%), ventricular tachycardia, conduction abnormalities, mitral valve abnormalities (42%), PVS (21%), ASD (6%), atrioventricular septal defects, coronary artery abnormalities | HCM (85%) |
| RAF1 | Mitral valve abnormalities (100%), PVS (40%), high risk of SCD | HCM (100%) |
| BRAF | - | HCM (60%–85%) |
| Costello syndrome | ||
| HRAS | Atrial tachycardia (56%), PVS | HCM (65%) |
| Cardiofaciocutaneous syndrome | ||
| BRAF1 | PVS (45%), ASD (30%), VSD (8%). Tetralogy of Fallot (7%) | HCM (40%) |
| MAP2K1-MAP2K2 | PVS (65%–100%), septal defects (15%) | HCM (40%) |
| KRAS | PVS (40%), mitral valve abnormalities (26%), ASD (20%), VSD (13%) | HCM (20%) |
Abbreviations: ASD, atrial septal defect; HCM, hypertrophic cardiomyopathy; PDA, patent ductus arteriosus; PVS, pulmonary valve stenosis; VSD, ventricular septal defect.