Table 3.
Genotypic value of monogenic cardiovascular diseases.1
| Monogenic cardiovascular diseases | Genotype-phenotype relationship |
|---|---|
| Hypertrophic cardiomyopathy | Carrying ≥2 sarcomere disease-causing mutations increases the risk of cardiovascular death in patients. |
| Arrhythmogenic right ventricular cardiomyopathy | Patients with a gene mutation have worse prognosis than those without gene mutations; patients with ≥2 gene mutations are prone to develop ventricular tachycardia/ventricular fibrillation and a high proportion of left ventricular dysfunction, heart failure, and heart transplantation. Adult males and females over 30 years old with the TMEM43 gene P. S358L mutation implanted with an ICD as a primary prevention can have increased survival rates. |
| Familial dilated cardiomyopathy | Patients with specific pathogenic genes have poor prognosis, and genetic testing is helpful for risk stratification. Patients with LMNA or DES gene mutations and cardiac conduction abnormalities (1–3 atrioventricular block) and/or a family history of sudden death are at higher risk of SCD. The DMD gene mutation may be associated with muscular dystrophy. |
| Metabolic cardiomyopathy | Due to extracardiac involvement, attention should be paid to the detection of related genes in patients with unexplained myocardial lesions with multi-system involvement, and infants or adolescents with onset of myocardial lesions. |
| Long QT syndrome | Patients with ≥2 disease-causing gene mutations or patients with congenital deafness with Jervell-Lange-Nielsen syndrome are at high risk of SCD, and preventive ICD implantation should be actively considered. LQTS1 patients should avoid strenuous exercise, especially swimming; LQTS2 patients should avoid sudden loud sounds (such as alarms, telephones, etc.). Patients with LQTS1 who have not been treated with beta blockers and have suffered cardiac arrest should first consider beta blocker oral therapy or left sympathetic neurotomy, rather than ICD implantation, unless the patient develops early onset. |
| Short QT syndrome | Quinidine shall be considered in patients diagnosed with SQTS1 by genetic testing. Sotalol should be used in patients with SQTS other than SQTS1. |
| Catecholaminergic polymorphic ventricular tachycardia | Patients with the RYR2 gene mutation have earlier onset and worse prognosis. Flecainide can effectively reduce the occurrence of ventricular arrhythmia in RYR2 gene mutation carriers. |
| Progressive cardiac conduction disease | Implantation of ICD may be useful in patients with pathogenic LMNA gene mutations and other clinical risk factors, such as paroxysmal ventricular tachycardia, male gender, and non-missense mutations, and especially patients with left ventricular ejection fraction <45%. |
| Familial hyperaldosteronism | Patients with FHA I fusion of CYP11B2/CYP11B1 are recommended to be treated with physiological doses of glucocorticoid. |
| Marfan syndrome | Personalized treatment can be prescribed based on genotypes and phenotypes, such as surgery in advance (e.g., when the maximum internal diameter of the thoracic aorta reaches 4.0–5.0 cm) to prevent dissection and rupture. For LDS patients with TGFBR1 and TGFBR2 pathogenic gene mutations, surgery can be considered with a maximum internal diameter of 4.2 cm in the thoracic aorta. Patients with LDS have a higher risk of developing aneurysms in locations other than aorta, and should be observed and monitored closely. |
| Thoracic aortic aneurysm and dissection | Personalized treatment can be prescribed based on genotypes and phenotypes, such as surgery in advance (e.g., when the maximum internal diameter of the thoracic aorta reaches 4.0–5.0 cm) to prevent dissection and rupture. For carriers of mutations in the pathogenic genes of TGFBR1 and TGFBR2, surgery can be considered with a maximum internal diameter of 4.2 cm in the thoracic aorta. For patients with ACTA2 gene mutations, surgery can be considered with a maximum internal diameter of 4.5 cm in the thoracic aorta. Patients with ACTA2 gene mutation have a higher risk of early stroke and coronary artery disease, and should be observed and monitored closely. |
| Ehlers-Danlos syndrome | Carriers of COL3A1 gene mutations are recommended to undergo surgery in advance (e.g., when the maximum internal diameter of the thoracic aorta reaches 4.0–5.0 cm) to avoid aortic rupture. Female patients have a higher risk of uterine rupture during pregnancy, and should be observed and monitored closely. |
| Pulmonary hypertension | Patients with BMPR2 mutations have worse clinical phenotypes and a worse prognosis. |
ICD: implantable cardioverter-defibrillator; SCD: sudden cardiac death; LQTS: long QT syndrome; SQTS: short QT syndrome; FHA: Familial hyperaldosteronism; LDS: Loeys-Dietz syndrome.