Cell Biochem Biophys DOI 10.1007/s12013-015-0551-6
ORIGINAL PAPER
Congenital Heart Disease: Causes, Diagnosis, Symptoms, and Treatments RongRong Sun • Min Liu • Lei Lu Yi Zheng • Peiying Zhang
•
Ó Springer Science+Business Media New York 2015
Abstract The congenital heart disease includes abnormalities in heart structure that occur before birth. Such defects occur in the fetus while it is developing in the uterus during pregnancy. About 500,000 adults have congenital heart disease in USA (WebMD, Congenital heart defects medications, www.WebMD.com/heart-disease/tc/ congenital-heart-defects-medications, 2014). 1 in every 100 children has defects in their heart due to genetic or chromosomal abnormalities, such as Down syndrome. The excessive alcohol consumption during pregnancy and use of medications, maternal viral infection, such as Rubella virus, measles (German), in the first trimester of pregnancy, all these are risk factors for congenital heart disease in children, and the risk increases if parent or sibling has a congenital heart defect. These are heart valves defects, atrial and ventricular septa defects, stenosis, the heart muscle abnormalities, and a hole inside wall of the heart which causes defect in blood circulation, heart failure, and eventual death. There are no particular symptoms of congenital heart disease, but shortness of breath and limited ability to do exercise, fatigue, abnormal sound of heart as heart murmur, which is diagnosed by a physician while listening to the heart beats. The echocardiogram or RongRong Sun and Min Liu have contributed equally to this work. R. Sun M. Liu L. Lu Y. Zheng Graduate School, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China P. Zhang (&) Department of Cardiology, Xuzhou Central Hospital, Affiliated Xuzhou Hospital, Medical School of Southeast University, Xuzhou Clinical Medical College of Nanjing University of Chinese Medicine, 199# South Jiefang Road, Xuzhou 221009, Jiangsu, China e-mail: [email protected]
transesophageal echocardiogram, electrocardiogram, chest X-ray, cardiac catheterization, and MRI methods are used to detect congenital heart disease. Several medications are given depending on the severity of this disease, and catheter method and surgery are required for serious cases to repair heart valves or heart transplantation as in endocarditis. For genetic study, first DNA is extracted from blood followed by DNA sequence analysis and any defect in nucleotide sequence of DNA is determined. For congenital heart disease, genes in chromosome 1 show some defects in nucleotide sequence. In this review the causes, diagnosis, symptoms, and treatments of congenital heart disease are described. Keywords Congenital heart disease Chromosomal abnormalities Viral infection
Introduction Congenital heart disease is the most common congenital anomaly in newborn babies [1]. Cardiac malformations have been produced in multiple experimental animal models, by perturbing selected molecules that function in the development pathways involved in myocyte specification, differentiation, or cardiac morphogenesis [1]. The precise genetic, epigenetic, environmental basis for various perturbations in human heart is not fully understood yet. The past 40 years of genetics research of heart diseases has indicated some advancement in the understanding of human genome analyses of rare Mendelian congenital heart disease families, and by DNA genes sequencing in the blood of patients of congenital heart disease cohorts. Although discovery of penetrance of disease gene mutations is known, and such studies have provided three
123
Cell Biochem Biophys
notable insights: (1) human congenital heart disease mutations impact a heterogeneous set of molecules that orchestrates cardiac development, (2) congenital heart disease mutations often alter gene-protein dosage, and (3) identical pathogenic congenital heart disease mutations cause a variety of distinct malformations, implying that higher-order interactions account for particular congenital heart disease phenotypes [1].
Genomic Studies of Congenital Heart Diseases The genomic technology and single nucleotide polymorphism array, the next generation sequencing of genes, and copy number variant platforms are making a rapid discovery to identify genetic causes of congenital heart disease. Although, such studies of congenital heart disease are sporadic presented, the detailed study of the genome from monogenic congenital heart disease parents and families will explain the genetic defects and architecture of congenital heart disease. The recent developments on the molecular genetics of congenital heart disease have been described by Wolf and Basson [2], as well as the interactions of genes and pathways during the development of congenital heart disease are presented. The discovery of specific genes that cause lesions and some previously identified genes are mentioned. T-box, NK, and GATA transcription factors have been associated with a variety of syndromic and isolated congenital heart defects. The redundant roles of NKx 2.5 and NKx 2.7 along with the interaction of NKx 2.7 with TBx 20 are elucidated. Other classes of transcription factors are also being elucidated. The 22q11.2 deletion and microduplication syndromes and their genetic interactions have been studied. The recent research also highlights PTPN11 and NOTCH1 in Noonam syndrome in the genetics of congenital heart disease. These genetic interactions will further provide a leading role in the better understanding of downstream transcriptional or signaling pathways of this genetic disease. The repair of genetic defects in blood or gene therapy may provide necessary treatment for the congenital heart disease in children, adolescents, and adults. The first step for genetic study is to extract DNA from blood samples by salt precipitation method to study the sequence of DNA in normal versus diseased blood samples, and observe the gene defects in the nucleotide sequence of DNA strand. Such earlier gene studies reported a gene defect on chromosome 1 for congenital heart disease [7].
(Tests and diagnosis) [3]. When blood does not flow normally through vessels, there is a sound of heart murmur in heart beat which is measured by stethoscope to examine the heart defects. Following tests are used to diagnose congenital heart disease. Fetal Echocardiogram An ultrasound waves test is done to create a picture of fetal heart and this test detects a heart defect before the birth, thus facilitate for a better treatment plan. Echocardiogram A regular echocardiogram is taken to diagnose a congenital heart defect after a child is born. An ultrasound test produces images of the heart defect. An echocardiogram also allows to observe heart beat of child and to identify abnormalities in the heart muscle and valves. Electrocardiogram The ECG test records the electrical activity of the heart and can help diagnose heart defects or rhythm problems. The electrodes are connected to a computer. The electrodes are placed on the chest of the patient which shows waves that indicate how the heart is beating in a child or an adult. Chest X-ray The chest X-ray is important for both, child and adult to see if the heart is enlarged, or if the lungs have extra blood or other fluid in them which can produce a heart failure. Pulse Oximetry This test measures how much oxygen is in the blood. A sensor is placed at the end of a finger to record the amount of oxygen in blood. Low oxygen in the blood indicates that child has a heart problem. Cardiac Catheterization In this test, a thin flexible tube (catheter) is inserted into a blood vessel at groin and guided through into the heart. The catheterization is sometimes necessary because it provides a detailed view of heart defects than an echocardiogram.
Diagnosis of Congenital Heart Disease Symptoms of Congenital Heart Disease The test and diagnosis of congenital heart disease in children or adults can be performed by taking blood pressure and electrocardiogram (ECG) or X-ray of heart patients
123
Congenital heart disease can have a range of symptoms due to conditions of different types of heart defects [4]. The
Cell Biochem Biophys
general signs of this disease include: excessive sweating, extreme tiredness, fatigue, poor feeding, rapid heartbeat, shortness of breath, chest pain, blue tinge to the skin (cyanosis), and clubbed fingernails. The congenital heart disease develops shortly after birth and the symptoms do not develop until early childhood or teenage years. However, some complications may develop during adulthood such as problem with growth and development of heart and body, the infections of respiratory tract, throat, lungs and sinuses, heart infection, endocarditis, pulmonary hypertension, high blood pressure, and the heart being unable to pump enough blood which can cause a heart failure.
Treatment of Congenital Heart Disease Heart surgeons repair congenital heart defects using catheter or surgical methods (NIH, National Heart, Lung and Blood Institute, US.) [5]. Many medications are known for the treatment of congenital heart disease. However, the use of catheter procedure is easier than surgery. A catheter (thin, flexible tube) is inserted into a vein or an artery, after the skin is punctured by a thin needle. In this case the openheart surgery can be avoided to repair the heart defect, but in severe cases of a hole in the inner wall of the heart, the stitches or a patch is needed to repair the inner wall and valves of heart.
Catheter Method The catheter method has been used successfully since the past 20 years by many heart surgeons to repair heart defects, such as atrial septal defect (ASD) and pulmonary valve stenosis. For ASD repair, a catheter is inserted into a vein in the groin (upper thigh) of patient and threads the tube to the heart’s septum. An umbrella-like device is attached to the catheter. When the catheter reaches the septum, the device is pushed out of the catheter. The device is placed so that it plugs the hole between the atria, secured in place, and catheter is withdrawn from the body. Within 6 months the normal tissue grows in and on the device, and the closure device does not need to be replaced as the child grows. In pulmonary valve stenosis, a catheter is inserted into a vein and is threaded to the pulmonary valve of the heart. A tiny balloon at the end of the catheter is quickly inflated to push apart the leaflets, or doors of the valve. The balloon is then deflated and the catheter and balloon are withdrawn. This method is used to repair any narrow valve in the heart. The catheter is guided by the use of echocardiography and transesophageal echocardiogram (TEE), and coronary angiography. The heart pictures are taken through the
esophagus, a passage leading from mouth to stomach. The TEE examines complex defects in the heart.
Surgery Method An open-heart surgery is performed in patients if heart defect is serious and cannot be repaired by catheter method. Usually one or more heart surgeries are required depending upon the severity of the congenital heart disease. The heart surgeons may use open-heart surgery to: close holes in the heart with stitches or a patch, repair or replace heart valves, widen arteries or openings to heart valves, repair complex defects, such as problems with the location of blood vessels near the heart or how they are formed. Rarely, babies are born with multiple defects that are too complex to repair and these babies need another new heart after their birth. In these cases, heart transplant surgery using a healthy heart of a child of same age and blood type is performed.
Types of Medications used for Congenital Heart Disease Many medications for the treatment of congenital heart defects are available as described by The Heart Disease Health Center ([6]). These medicines are necessary for patients to correct the defect in the heart and help to repair it. Certain medications may have to be taken for a long time to keep the heart beating properly and for the appropriate blood circulation in the body. For many heart defects and diseases, the use of diuretics, digoxin, vasodilators, and antiarrhythmic drugs have been recommended. The heart defects can also be treated by prostaglandins and prostaglandin inhibitors to keep the fetal blood vessel opened, and is called as ductus arteriosus, that normally closes at birth. Antibiotics are used for endocarditis before surgery. Aspirin is used as a blood thinner or anticoagulant which lowers the risk of blood clots in the heart or blood vessels. However, many heart defects can be a part of genetic and chromosomal syndromes. Some of these syndromes may be passed down through parents and families. The examples are: DiGeorge syndrome, Down syndrome, Marfan syndrome, Noonan syndrome, Trisomy 13, and Turner syndrome. For congenital heart disease, the genetic study of defective genes or DNA sequence is important to observe to identify which gene has abnormal nucleotide sequence. Gene therapy using new, modern genetic methods of RNA and DNA technologies can repair such defective genes in DNA sequences. Moreover, genomic study is time consuming and will take 100 years or more to understand correct human genome. Certain genes are defective from childhood so how to repair their DNA
123
Cell Biochem Biophys
sequences or to repair and correct their genetic materials by gene therapy is a challenging research for future [1]. However, various types of congenital heart defects or diseases have been described by [4], such as, aortic valve stenosis, coarctation of the aorta, Ebstein’s anomaly, patent ductus arteriosus, pulmonary valve stenosis, septal defects (including atrial septal defects and ventricular septal defects), single ventricle defects (including tricuspid atresia, and hypoplastic left heart syndrome), Tetralogy of Fallot, total anomalous pulmonary venous connection, transposition of the great arteries, and truncus arteriosus. There is a need for the genetic research of blood DNA sequences to further study congenital heart defects in children after birth, in adolescents, and adult patients.
Conclusion Congenital heart disease is the most common congenital anomaly in newborn babies and adolescents. The heart genetics research since past 40 years has shown some advancement in the understanding of human genome analyses of rare Mendelian congenital heart disease by gene sequencing, and blood DNA analyses of heart disease cohorts [1]. About 500,000 persons have congenital heart disease in USA [6]. 1 in 100 children and young teenagers have defects in their heart’s inner-walls or valves which is due to genetic or chromosomal abnormalities, such as Down syndrome. The catheter and surgery procedures can repair the heart defects in congenital heart disease. The diagnosis of this disease can be done by ECG and X-ray and other methods. Some medications are useful to protect the heart
123
from further defects or damages and heart failure in children, teenagers, or adults. The future studies of blood DNA sequences and human genome are necessary to understand the genetic defects and how to repair these by gene therapy. The discovery of new medications is also important for this heart disease.
References 1. Fahed, AC., Gelb, BD., Seidman, JG., Seidman, CF. (2014). Genetics of congenital heart disease. The glass half empty. Harvard University Medical School, Boston. Circulation Research, American Heart Association. www.nature.com/ncomms/2014/ 140428/ncomms4680/ris/ncomms4680refs.ris. 2. Wolf, M., & Basson, C. T. (2010). The molecular genetics of congenital heart disease: A review of recent developments. Current Opinion in Cardiology, 25(3), 192–197. doi:10.1097/ HCO.0b013e328337b4ce. 3. Mayo Clinic, USA. (2014). The diagnosis of congenital heart disease.www.Mayoclinic.org/diseases-conditions/congenital-heartdefects/basics/tests-diagnosis/con-20034017. 4. NHS Choices, UK. (2014). The symptoms of congenital heart disease. www.nhs.uk/conditions.congenital-heart-disease/pages/ symptoms.aspx. 5. NIH (2014) National Heart, Lung and Blood Institute, USA. How are congenital heart defects treated? www.nhlbi.nih.gov/healthy/ health-topics/topics/chd/treatment.html. 6. WebMD (2014) Congenital heart defects medications. The Heart Disease Health Center, USA. www.WebMD.com/heart-disease/tc/ congenital-heart-defects-medications. 7. Sheffield, V. C., Pierpont, M. E., Nishimura, D., Beck, J. S., Burns, T. L., Anne Berg, M., et al. (1996). Identification of a complex congenital heart defect susceptibility locus by using DNA pooling and shared segment analysis. Human Molecular Genetics, 6(1), 117–121.
ORIGINAL PAPER
Congenital Heart Disease: Causes, Diagnosis, Symptoms, and Treatments RongRong Sun • Min Liu • Lei Lu Yi Zheng • Peiying Zhang
•
Ó Springer Science+Business Media New York 2015
Abstract The congenital heart disease includes abnormalities in heart structure that occur before birth. Such defects occur in the fetus while it is developing in the uterus during pregnancy. About 500,000 adults have congenital heart disease in USA (WebMD, Congenital heart defects medications, www.WebMD.com/heart-disease/tc/ congenital-heart-defects-medications, 2014). 1 in every 100 children has defects in their heart due to genetic or chromosomal abnormalities, such as Down syndrome. The excessive alcohol consumption during pregnancy and use of medications, maternal viral infection, such as Rubella virus, measles (German), in the first trimester of pregnancy, all these are risk factors for congenital heart disease in children, and the risk increases if parent or sibling has a congenital heart defect. These are heart valves defects, atrial and ventricular septa defects, stenosis, the heart muscle abnormalities, and a hole inside wall of the heart which causes defect in blood circulation, heart failure, and eventual death. There are no particular symptoms of congenital heart disease, but shortness of breath and limited ability to do exercise, fatigue, abnormal sound of heart as heart murmur, which is diagnosed by a physician while listening to the heart beats. The echocardiogram or RongRong Sun and Min Liu have contributed equally to this work. R. Sun M. Liu L. Lu Y. Zheng Graduate School, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China P. Zhang (&) Department of Cardiology, Xuzhou Central Hospital, Affiliated Xuzhou Hospital, Medical School of Southeast University, Xuzhou Clinical Medical College of Nanjing University of Chinese Medicine, 199# South Jiefang Road, Xuzhou 221009, Jiangsu, China e-mail: [email protected]
transesophageal echocardiogram, electrocardiogram, chest X-ray, cardiac catheterization, and MRI methods are used to detect congenital heart disease. Several medications are given depending on the severity of this disease, and catheter method and surgery are required for serious cases to repair heart valves or heart transplantation as in endocarditis. For genetic study, first DNA is extracted from blood followed by DNA sequence analysis and any defect in nucleotide sequence of DNA is determined. For congenital heart disease, genes in chromosome 1 show some defects in nucleotide sequence. In this review the causes, diagnosis, symptoms, and treatments of congenital heart disease are described. Keywords Congenital heart disease Chromosomal abnormalities Viral infection
Introduction Congenital heart disease is the most common congenital anomaly in newborn babies [1]. Cardiac malformations have been produced in multiple experimental animal models, by perturbing selected molecules that function in the development pathways involved in myocyte specification, differentiation, or cardiac morphogenesis [1]. The precise genetic, epigenetic, environmental basis for various perturbations in human heart is not fully understood yet. The past 40 years of genetics research of heart diseases has indicated some advancement in the understanding of human genome analyses of rare Mendelian congenital heart disease families, and by DNA genes sequencing in the blood of patients of congenital heart disease cohorts. Although discovery of penetrance of disease gene mutations is known, and such studies have provided three
123
Cell Biochem Biophys
notable insights: (1) human congenital heart disease mutations impact a heterogeneous set of molecules that orchestrates cardiac development, (2) congenital heart disease mutations often alter gene-protein dosage, and (3) identical pathogenic congenital heart disease mutations cause a variety of distinct malformations, implying that higher-order interactions account for particular congenital heart disease phenotypes [1].
Genomic Studies of Congenital Heart Diseases The genomic technology and single nucleotide polymorphism array, the next generation sequencing of genes, and copy number variant platforms are making a rapid discovery to identify genetic causes of congenital heart disease. Although, such studies of congenital heart disease are sporadic presented, the detailed study of the genome from monogenic congenital heart disease parents and families will explain the genetic defects and architecture of congenital heart disease. The recent developments on the molecular genetics of congenital heart disease have been described by Wolf and Basson [2], as well as the interactions of genes and pathways during the development of congenital heart disease are presented. The discovery of specific genes that cause lesions and some previously identified genes are mentioned. T-box, NK, and GATA transcription factors have been associated with a variety of syndromic and isolated congenital heart defects. The redundant roles of NKx 2.5 and NKx 2.7 along with the interaction of NKx 2.7 with TBx 20 are elucidated. Other classes of transcription factors are also being elucidated. The 22q11.2 deletion and microduplication syndromes and their genetic interactions have been studied. The recent research also highlights PTPN11 and NOTCH1 in Noonam syndrome in the genetics of congenital heart disease. These genetic interactions will further provide a leading role in the better understanding of downstream transcriptional or signaling pathways of this genetic disease. The repair of genetic defects in blood or gene therapy may provide necessary treatment for the congenital heart disease in children, adolescents, and adults. The first step for genetic study is to extract DNA from blood samples by salt precipitation method to study the sequence of DNA in normal versus diseased blood samples, and observe the gene defects in the nucleotide sequence of DNA strand. Such earlier gene studies reported a gene defect on chromosome 1 for congenital heart disease [7].
(Tests and diagnosis) [3]. When blood does not flow normally through vessels, there is a sound of heart murmur in heart beat which is measured by stethoscope to examine the heart defects. Following tests are used to diagnose congenital heart disease. Fetal Echocardiogram An ultrasound waves test is done to create a picture of fetal heart and this test detects a heart defect before the birth, thus facilitate for a better treatment plan. Echocardiogram A regular echocardiogram is taken to diagnose a congenital heart defect after a child is born. An ultrasound test produces images of the heart defect. An echocardiogram also allows to observe heart beat of child and to identify abnormalities in the heart muscle and valves. Electrocardiogram The ECG test records the electrical activity of the heart and can help diagnose heart defects or rhythm problems. The electrodes are connected to a computer. The electrodes are placed on the chest of the patient which shows waves that indicate how the heart is beating in a child or an adult. Chest X-ray The chest X-ray is important for both, child and adult to see if the heart is enlarged, or if the lungs have extra blood or other fluid in them which can produce a heart failure. Pulse Oximetry This test measures how much oxygen is in the blood. A sensor is placed at the end of a finger to record the amount of oxygen in blood. Low oxygen in the blood indicates that child has a heart problem. Cardiac Catheterization In this test, a thin flexible tube (catheter) is inserted into a blood vessel at groin and guided through into the heart. The catheterization is sometimes necessary because it provides a detailed view of heart defects than an echocardiogram.
Diagnosis of Congenital Heart Disease Symptoms of Congenital Heart Disease The test and diagnosis of congenital heart disease in children or adults can be performed by taking blood pressure and electrocardiogram (ECG) or X-ray of heart patients
123
Congenital heart disease can have a range of symptoms due to conditions of different types of heart defects [4]. The
Cell Biochem Biophys
general signs of this disease include: excessive sweating, extreme tiredness, fatigue, poor feeding, rapid heartbeat, shortness of breath, chest pain, blue tinge to the skin (cyanosis), and clubbed fingernails. The congenital heart disease develops shortly after birth and the symptoms do not develop until early childhood or teenage years. However, some complications may develop during adulthood such as problem with growth and development of heart and body, the infections of respiratory tract, throat, lungs and sinuses, heart infection, endocarditis, pulmonary hypertension, high blood pressure, and the heart being unable to pump enough blood which can cause a heart failure.
Treatment of Congenital Heart Disease Heart surgeons repair congenital heart defects using catheter or surgical methods (NIH, National Heart, Lung and Blood Institute, US.) [5]. Many medications are known for the treatment of congenital heart disease. However, the use of catheter procedure is easier than surgery. A catheter (thin, flexible tube) is inserted into a vein or an artery, after the skin is punctured by a thin needle. In this case the openheart surgery can be avoided to repair the heart defect, but in severe cases of a hole in the inner wall of the heart, the stitches or a patch is needed to repair the inner wall and valves of heart.
Catheter Method The catheter method has been used successfully since the past 20 years by many heart surgeons to repair heart defects, such as atrial septal defect (ASD) and pulmonary valve stenosis. For ASD repair, a catheter is inserted into a vein in the groin (upper thigh) of patient and threads the tube to the heart’s septum. An umbrella-like device is attached to the catheter. When the catheter reaches the septum, the device is pushed out of the catheter. The device is placed so that it plugs the hole between the atria, secured in place, and catheter is withdrawn from the body. Within 6 months the normal tissue grows in and on the device, and the closure device does not need to be replaced as the child grows. In pulmonary valve stenosis, a catheter is inserted into a vein and is threaded to the pulmonary valve of the heart. A tiny balloon at the end of the catheter is quickly inflated to push apart the leaflets, or doors of the valve. The balloon is then deflated and the catheter and balloon are withdrawn. This method is used to repair any narrow valve in the heart. The catheter is guided by the use of echocardiography and transesophageal echocardiogram (TEE), and coronary angiography. The heart pictures are taken through the
esophagus, a passage leading from mouth to stomach. The TEE examines complex defects in the heart.
Surgery Method An open-heart surgery is performed in patients if heart defect is serious and cannot be repaired by catheter method. Usually one or more heart surgeries are required depending upon the severity of the congenital heart disease. The heart surgeons may use open-heart surgery to: close holes in the heart with stitches or a patch, repair or replace heart valves, widen arteries or openings to heart valves, repair complex defects, such as problems with the location of blood vessels near the heart or how they are formed. Rarely, babies are born with multiple defects that are too complex to repair and these babies need another new heart after their birth. In these cases, heart transplant surgery using a healthy heart of a child of same age and blood type is performed.
Types of Medications used for Congenital Heart Disease Many medications for the treatment of congenital heart defects are available as described by The Heart Disease Health Center ([6]). These medicines are necessary for patients to correct the defect in the heart and help to repair it. Certain medications may have to be taken for a long time to keep the heart beating properly and for the appropriate blood circulation in the body. For many heart defects and diseases, the use of diuretics, digoxin, vasodilators, and antiarrhythmic drugs have been recommended. The heart defects can also be treated by prostaglandins and prostaglandin inhibitors to keep the fetal blood vessel opened, and is called as ductus arteriosus, that normally closes at birth. Antibiotics are used for endocarditis before surgery. Aspirin is used as a blood thinner or anticoagulant which lowers the risk of blood clots in the heart or blood vessels. However, many heart defects can be a part of genetic and chromosomal syndromes. Some of these syndromes may be passed down through parents and families. The examples are: DiGeorge syndrome, Down syndrome, Marfan syndrome, Noonan syndrome, Trisomy 13, and Turner syndrome. For congenital heart disease, the genetic study of defective genes or DNA sequence is important to observe to identify which gene has abnormal nucleotide sequence. Gene therapy using new, modern genetic methods of RNA and DNA technologies can repair such defective genes in DNA sequences. Moreover, genomic study is time consuming and will take 100 years or more to understand correct human genome. Certain genes are defective from childhood so how to repair their DNA
123
Cell Biochem Biophys
sequences or to repair and correct their genetic materials by gene therapy is a challenging research for future [1]. However, various types of congenital heart defects or diseases have been described by [4], such as, aortic valve stenosis, coarctation of the aorta, Ebstein’s anomaly, patent ductus arteriosus, pulmonary valve stenosis, septal defects (including atrial septal defects and ventricular septal defects), single ventricle defects (including tricuspid atresia, and hypoplastic left heart syndrome), Tetralogy of Fallot, total anomalous pulmonary venous connection, transposition of the great arteries, and truncus arteriosus. There is a need for the genetic research of blood DNA sequences to further study congenital heart defects in children after birth, in adolescents, and adult patients.
Conclusion Congenital heart disease is the most common congenital anomaly in newborn babies and adolescents. The heart genetics research since past 40 years has shown some advancement in the understanding of human genome analyses of rare Mendelian congenital heart disease by gene sequencing, and blood DNA analyses of heart disease cohorts [1]. About 500,000 persons have congenital heart disease in USA [6]. 1 in 100 children and young teenagers have defects in their heart’s inner-walls or valves which is due to genetic or chromosomal abnormalities, such as Down syndrome. The catheter and surgery procedures can repair the heart defects in congenital heart disease. The diagnosis of this disease can be done by ECG and X-ray and other methods. Some medications are useful to protect the heart
123
from further defects or damages and heart failure in children, teenagers, or adults. The future studies of blood DNA sequences and human genome are necessary to understand the genetic defects and how to repair these by gene therapy. The discovery of new medications is also important for this heart disease.
References 1. Fahed, AC., Gelb, BD., Seidman, JG., Seidman, CF. (2014). Genetics of congenital heart disease. The glass half empty. Harvard University Medical School, Boston. Circulation Research, American Heart Association. www.nature.com/ncomms/2014/ 140428/ncomms4680/ris/ncomms4680refs.ris. 2. Wolf, M., & Basson, C. T. (2010). The molecular genetics of congenital heart disease: A review of recent developments. Current Opinion in Cardiology, 25(3), 192–197. doi:10.1097/ HCO.0b013e328337b4ce. 3. Mayo Clinic, USA. (2014). The diagnosis of congenital heart disease.www.Mayoclinic.org/diseases-conditions/congenital-heartdefects/basics/tests-diagnosis/con-20034017. 4. NHS Choices, UK. (2014). The symptoms of congenital heart disease. www.nhs.uk/conditions.congenital-heart-disease/pages/ symptoms.aspx. 5. NIH (2014) National Heart, Lung and Blood Institute, USA. How are congenital heart defects treated? www.nhlbi.nih.gov/healthy/ health-topics/topics/chd/treatment.html. 6. WebMD (2014) Congenital heart defects medications. The Heart Disease Health Center, USA. www.WebMD.com/heart-disease/tc/ congenital-heart-defects-medications. 7. Sheffield, V. C., Pierpont, M. E., Nishimura, D., Beck, J. S., Burns, T. L., Anne Berg, M., et al. (1996). Identification of a complex congenital heart defect susceptibility locus by using DNA pooling and shared segment analysis. Human Molecular Genetics, 6(1), 117–121.
