Врожденные пороки сердца: причины, генетика и диагностика.

Defect in the structure of the heart that is present at birth
The cause of a congenital heart defect is often unknown. Risk factors include certain infections during pregnancy such as rubella, use of certain medications or drugs such as alcohol or tobacco, parents being closely related, or poor nutritional status or obesity in the mother. Having a parent with a congenital heart defect is also a risk factor. or a heart transplant may be required. Some children have no signs while others may exhibit shortness of breath, cyanosis, fainting, heart murmur, under development of limbs and muscles, poor feeding or growth, or respiratory infections. Congenital heart defects cause abnormal heart structure resulting in production of certain sounds called heart murmur. These can sometimes be detected by auscultation; however, not all heart murmurs are caused by congenital heart defects.

The cause of congenital heart disease may be genetic, environmental, or a combination of both. They are described in the table below. +Genetic lesionsAttributable percentExamplesPrimary genetic testing methodAneuploidies5–8%Survivable autosomal trisomies (chromosomes 13, 18, 21), chromosome X monosomy (Turner syndrome)KaryotypingCopy number variants10–12%22q11.2 deletion/duplication (velocardiofacial/DiGeorge syndrome), 1q21.1 deletion/duplication, 8p23.1 deletion/duplication, 15q11.2 deletion (Burnside Butler syndrome)Array comparative genomic hybridization (also known as chromosomal microarray analysis)Inherited protein coding single nucleotide variant (SNV) or small insertion/deletion (indel)3–5%Holt–Oram syndrome, Noonan syndrome, Alagille syndromeGene panelDe novo protein coding SNV or indel~10% Several proteins that interact with MYH6 are also associated with cardiac defects. The transcription factor GATA4 forms a complex with the TBX5 which interacts with MYH6. Another factor, the homeobox (developmental) gene, NKX2 5 also interacts with MYH6. Mutations of all these proteins are associated with both atrial and ventricular septal defects; In addition, NKX2 5 is associated with defects in the electrical conduction of the heart and TBX5 is related to the Holt–Oram syndrome which includes electrical conduction defects and abnormalities of the upper limb. The Wnt signaling co factors BCL9, BCL9L and PYGO might be part of these molecular pathways, as when their genes are mutated, this causes phenotypes similar to the features present in Holt Oram syndrome. Another T box gene, TBX1, is involved in velo cardio facial syndrome DiGeorge syndrome, the most common deletion which has extensive symptoms including defects of the cardiac outflow tract including tetralogy of Fallot. Upper limb abnormalities Small or absent thymus Small or absent parathyroids Facial abnormalities

The notch signaling pathway, a regulatory mechanism for cell growth and differentiation, plays broad roles in several aspects of cardiac development. Notch elements are involved in determination of the right and left sides of the body plan, so the directional folding of the heart tube can be impacted. Notch signaling is involved early in the formation of the endocardial cushions and continues to be active as the develop into the septa and valves. It is also involved in the development of the ventricular wall and the connection of the outflow tract to the great vessels. Mutations in the gene for one of the notch ligands, Jagged1, are identified in the majority of examined cases of arteriohepatic dysplasia (Alagille syndrome), characterized by defects of the great vessels (pulmonary artery stenosis), heart (tetralogy of Fallot in 13% of cases), liver, eyes, face, and bones. Though less than 1% of all cases, where no defects are found in the Jagged1 gene, defects are found in Notch2 gene. In 10% of cases, no mutation is found in either gene. For another member of the gene family, mutations in the Notch1 gene are associated with bicuspid aortic valve, a valve with two leaflets instead of three. Notch1 is also associated with calcification of the aortic valve, the third most common cause of heart disease in adults. Mutations of a cell regulatory mechanism, the Ras/MAPK pathway are responsible for a variety of syndromes, including Noonan syndrome, LEOPARD syndrome, Costello syndrome and cardiofaciocutaneous syndrome in which there is cardiac involvement. While the conditions listed are known genetic causes, there are likely many other genes which are more subtle. It is known that the risk for congenital heart defects is higher when there is a close relative with one. Alcohol exposure in the father also appears to increase the risk of congenital heart defects. Being overweight or obese increases the risk of congenital heart disease. A distinct physiological mechanism has not been identified to explain the link between maternal obesity and CHD, but both pre pregnancy folate deficiency and diabetes have been implicated in some studies.

Many congenital heart defects can be diagnosed prenatally by fetal echocardiography. This is a test which can be done during the second trimester of pregnancy, when the woman is about 18–24 weeks pregnant. It can be an abdominal ultrasound or transvaginal ultrasound. If a baby is born with cyanotic heart disease, the diagnosis is usually made shortly after birth due to the blue colour of their skin (called cyanosis).

Hypoplasia can affect the heart, typically resulting in the underdevelopment of the right ventricle or the left ventricle. This causes only one side of the heart to be capable of pumping blood to the body and lungs effectively. Hypoplasia of the heart is rare but is the most serious form of CHD. It is called hypoplastic left heart syndrome when it affects the left side of the heart and hypoplastic right heart syndrome when it affects the right side of the heart. In both conditions, the presence of a patent ductus arteriosus (and, when hypoplasia affects the right side of the heart, a patent foramen ovale) is vital to the infant's ability to survive until emergency heart surgery can be performed, since without these pathways blood cannot circulate to the body (or lungs, depending on which side of the heart is defective). Hypoplasia of the heart is generally a cyanotic heart defect.

Obstructive defects occur when heart valves, arteries, or veins are abnormally narrow or blocked. Common defects include pulmonic stenosis, aortic stenosis, and coarctation of the aorta, with other types such as bicuspid aortic valve stenosis and subaortic stenosis being comparatively rare. Any narrowing or blockage can cause heart enlargement or hypertension.

The septum is a wall of tissue which separates the left heart from the right heart. Defects in the interatrial septum or the interventricular septum allow blood to flow from the left side of the heart to the right, reducing the heart's efficiency. although approximately 30% of adults have a type of atrial septal defect called probe patent foramen ovale.

Cyanotic heart defects are called such because they result in cyanosis, a bluish grey discoloration of the skin due to a lack of oxygen in the body. Such defects include persistent truncus arteriosus, total anomalous pulmonary venous connection, tetralogy of Fallot, transposition of the great vessels, and tricuspid atresia.

Supporting people with chronic diseases such as congenital heart disease with emotional problems and mental health is a treatment consideration. Since some people with congenital heart disease have a lower quality of life that is related to their condition, some people may struggle with finding a job, engaging in physical exercise, with their fertility, and clinical depression as examples. An estimated 31% of adults with congenital heart disease also have mood disorders. For congenital heart defects that arise without a family history (de novo), the recurrence risk in offspring is 3–5%. This risk is higher in left ventricular outflow tract obstructions, heterotaxy, and atrioventricular septal defects.