Congenital heart defect
Encyclopedia
A congenital heart defect (CHD) is a defect in the structure of the heart
and great vessels
which is present at birth
. Many types of heart defects exist, most of which either obstruct blood flow
in the heart or vessels
near it, or cause blood to flow
through the heart in an abnormal pattern. Other defects, such as long QT syndrome
, affect the heart
's rhythm. Heart defects are among the most common birth defects and are the leading cause of birth defect-related deaths. Approximately 9 people in 1000 are born with a congenital heart defect. Many defects don't need treatment, but some complex congenital heart defects require medication or surgery.
, syncope
, heart murmur
, under-developing 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.
:
Ventricular septal defect (VSD), atrial septal defects, and tetralogy of Fallot are the most common congenital heart defects seen in the VACTERL association. Less common defects in the association are truncus arteriosus, and transposition of the great arteries.
") has been studied extensively and the genes that control the process are being elucidated.
Around day 15 of development, the cells that will become the heart exist in two horseshoe shaped bands of the middle tissue layer (mesoderm
), and some cells migrate from portion of the outer layer (ectoderm
), the neural crest
which is the source of a variety of cells found throughout the body. On day 19 of development, a pair of vascular elements, the "endocardial tubes", form. The tubes fuse when cells between then undergo programmed death and cells from the first heart field migrate to the tube, and form a ring of heart cells (myocyte
s) around it by day 21. On day 22, the heart begins to beat and by day 24, blood is circulating.
At day 22, the circulatory system is bilaterally symmetrical with paired vessels on each side and the heart consisting of a simple tube located in the midline of the body layout. The portion that will become the atria and will be located closest to the head are the most distant from the head. From days 23 through 28, the heart tube folds and twists, with the future ventricles
moving left of center (the ultimate location of the heart) and the atria moving towards the head.
On day 28, areas of tissue in the heart tube begin to expand inwards; after about two weeks, these expansions, the membranous "septum primum
" and the muscular "endocardial cushions
", fuse to form the four heart chambers of the heart. A failure to fuse properly will result in a defect that may allow blood to leak between chambers. After this happens, cells which have migrated from the neural crest begin to divide the bulbus cordis
, the main outflow tract is divided in two by the growth a spiraling septum, becoming the great vessels—the ascending segment of the aorta and the pulmonary trunk. If the separation is incomplete, the result is a "persistent truncus arteriosis". The vessels may be reversed ("transposition of the great vessels
"). The two halves of the split tract must migrate into the correct positions over the appropriate ventricles. A failure may result in some blood flowing into the wrong vessel (e.g. overriding aorta
). The four chambered heart and the great vessels have features required for fetal growth. The lungs are unexpanded and cannot accommodate the full circulatory volume. Two structures exist to shunt blood flow away from the lungs. Cells in part of the septum primum die creating a hole while muscle cells, the "septum secundum
", grow along the right atrial side the septum primum, except for one region, leaving a gap through which blood can pass from the right artium to the left atrium, the foramen ovale
. A small vessel, the ductus arteriosus
allows blood from the pulmonary artery
to pass to the aorta.
21
, 13, and 18 cause about 5-8% of cases of CHD, with trisomy 21 being the most common genetic cause. Small chromosomal abnormalities also frequently lead to congenital heart disease, and examples include microdeletion of the long arm of chromosome 22 (22q11, DiGeorge syndrome
), the long arm of chromosome 1 (1q21), the short arm of chromosome 8 (8p23) and many other, less recurrent regions of the genome, as shown by high resolution genome-wide screening (Array comparative genomic hybridization
).
The genes regulating the complex developmental sequence have only been partly elucidated. Some genes are associated with specific defects. A number of genes have been associated with cardiac manifestations. Mutations of a heart muscle protein, α-myosin heavy chain (MYH6
) are associated with atrial septal defects. 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. 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
.
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.
Mutation 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.
s (Rubella
), drugs
(alcohol
, hydantoin
, lithium
and thalidomide
) and maternal illness (diabetes mellitus
, phenylketonuria
, and systemic lupus erythematosus
).
A distinct physiological mechanism has not been identified to explain the link between maternal obesity and CHD, but both prepregnancy folate deficiency and diabetes have been implicated in some studies. Identification of the mechanism could aid health officials to develop reduction strategies and curb CHD’s prevalence in this preventable situation.
can affect the heart, typically resulting in the underdevelopment of the right ventricle
or the left ventricle
. This results in only one side of the heart capable of pumping blood to the body and lung
s 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
.
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
.
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. Ventricular septal defect
s are collectively the most common type of CHD, although approximately 30% of adults have a type of atrial septal defect
called probe patent foramen ovale.
s 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
.
Some conditions affect the great vessels or other vessels in close proximity to the heart, but not the heart itself, but are often classified as congenital heart defects.
Some constellations of multiple defects are commonly found together.
Most patients require life-long specialized cardiac care, first with a pediatic cardiologist and later with and adult congenital cardiologist. There are more than 1.8 million adults living with congenital heart defects.
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
and great vessels
Great vessels
Great vessels is a term used to refer collectively to the four large vessels that bring blood to and from the heart. These are:*Superior vena cava*Inferior vena cava*Pulmonary artery*AortaAll four pulmonary veins are considered apart of the great vessels...
which is present at birth
Birth
Birth is the act or process of bearing or bringing forth offspring. The offspring is brought forth from the mother. The time of human birth is defined as the time at which the fetus comes out of the mother's womb into the world...
. Many types of heart defects exist, most of which either obstruct blood flow
Blood flow
Blood flow is the continuous running of blood in the cardiovascular system.The human body is made up of several processes all carrying out various functions. We have the gastrointestinal system which aids the digestion and the absorption of food...
in the heart or vessels
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
near it, or cause blood to flow
Circulatory system
The circulatory system is an organ system that passes nutrients , gases, hormones, blood cells, etc...
through the heart in an abnormal pattern. Other defects, such as long QT syndrome
Long QT syndrome
The long QT syndrome is a rare inborn heart condition in which delayed repolarization of the heart following a heartbeat increases the risk of episodes of torsade de pointes . These episodes may lead to palpitations, fainting and sudden death due to ventricular fibrillation...
, affect the heart
Cardiac cycle
The cardiac cycle is a term referring to all or any of the events related to the flow or blood pressure that occurs from the beginning of one heartbeat to the beginning of the next. The frequency of the cardiac cycle is described by the heart rate. Each beat of the heart involves five major stages...
's rhythm. Heart defects are among the most common birth defects and are the leading cause of birth defect-related deaths. Approximately 9 people in 1000 are born with a congenital heart defect. Many defects don't need treatment, but some complex congenital heart defects require medication or surgery.
Signs and symptoms
Signs and symptoms are related to the type and severity of the heart defect. Symptoms frequently present early in life, but it's possible for some CHDs to go undetected throughout life. Some children have no signs while others may exhibit shortness of breath, cyanosisCyanosis
Cyanosis is the appearance of a blue or purple coloration of the skin or mucous membranes due to the tissues near the skin surface being low on oxygen. The onset of cyanosis is 2.5 g/dL of deoxyhemoglobin. The bluish color is more readily apparent in those with high hemoglobin counts than it is...
, syncope
Syncope (medicine)
Syncope , the medical term for fainting, is precisely defined as a transient loss of consciousness and postural tone characterized by rapid onset, short duration, and spontaneous recovery due to global cerebral hypoperfusion that most often results from hypotension.Many forms of syncope are...
, heart murmur
Heart murmur
Murmurs are extra heart sounds that are produced as a result of turbulent blood flow that is sufficient to produce audible noise. Most murmurs can only be heard with the assistance of a stethoscope ....
, under-developing 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
Heart murmur
Murmurs are extra heart sounds that are produced as a result of turbulent blood flow that is sufficient to produce audible noise. Most murmurs can only be heard with the assistance of a stethoscope ....
. These can sometimes be detected by auscultation
Auscultation
Auscultation is the term for listening to the internal sounds of the body, usually using a stethoscope...
; however, not all heart murmurs are caused by congenital heart defects.
Associated symptoms
Congenital heart defects are associated with an increased incidence of some other symptoms, together being called the VACTERL associationVACTERL association
VATER syndrome or VACTERL association is a non-random association of birth defects. The reason it is called an association, rather than a syndrome is that while all of the birth defects are linked, it is still unknown which genes or sets of genes cause these birth defects to occur.Each child with...
:
- V - Vertebral anomalies
- A - Anal atresia
- C - Cardiovascular anomalies
- T - Tracheoesophageal fistulaTracheoesophageal fistulaA tracheoesophageal fistula is an abnormal connection between the esophagus and the trachea...
- E - Esophageal atresiaEsophageal atresiaEsophageal atresia is a congenital medical condition which affects the alimentary tract. It causes the esophagus to end in a blind-ended pouch rather than connecting normally to the stomach. It comprises a variety of congenital anatomic defects that are caused by an abnormal embryological...
- R - Renal (Kidney)KidneyThe kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
and/or radialRadius (bone)The radius is one of the two large bones of the forearm, the other being the ulna. It extends from the lateral side of the elbow to the thumb side of the wrist and runs parallel to the ulna, which exceeds it in length and size. It is a long bone, prism-shaped and slightly curved longitudinally...
anomalies - L - Limb defects
Ventricular septal defect (VSD), atrial septal defects, and tetralogy of Fallot are the most common congenital heart defects seen in the VACTERL association. Less common defects in the association are truncus arteriosus, and transposition of the great arteries.
Embryology
There is a complex sequence of events that result in a well formed heart at birth and disruption of any portion may result in a defect. The orderly timing of cell growth, cell migration, and programmed cell death ("apoptosisApoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
") has been studied extensively and the genes that control the process are being elucidated.
Around day 15 of development, the cells that will become the heart exist in two horseshoe shaped bands of the middle tissue layer (mesoderm
Mesoderm
In all bilaterian animals, the mesoderm is one of the three primary germ cell layers in the very early embryo. The other two layers are the ectoderm and endoderm , with the mesoderm as the middle layer between them.The mesoderm forms mesenchyme , mesothelium, non-epithelial blood corpuscles and...
), and some cells migrate from portion of the outer layer (ectoderm
Ectoderm
The "ectoderm" is one of the three primary germ cell layers in the very early embryo. The other two layers are the mesoderm and endoderm , with the ectoderm as the most exterior layer...
), the neural crest
Neural crest
Neural crest cells are a transient, multipotent, migratory cell population unique to vertebrates that gives rise to a diverse cell lineage including melanocytes, craniofacial cartilage and bone, smooth muscle, peripheral and enteric neurons and glia....
which is the source of a variety of cells found throughout the body. On day 19 of development, a pair of vascular elements, the "endocardial tubes", form. The tubes fuse when cells between then undergo programmed death and cells from the first heart field migrate to the tube, and form a ring of heart cells (myocyte
Myocyte
A myocyte is the type of cell found in muscles. They arise from myoblasts.Each myocyte contains myofibrils, which are long, long chains of sarcomeres, the contractile units of the cell....
s) around it by day 21. On day 22, the heart begins to beat and by day 24, blood is circulating.
At day 22, the circulatory system is bilaterally symmetrical with paired vessels on each side and the heart consisting of a simple tube located in the midline of the body layout. The portion that will become the atria and will be located closest to the head are the most distant from the head. From days 23 through 28, the heart tube folds and twists, with the future ventricles
Ventricle (heart)
In the heart, a ventricle is one of two large chambers that collect and expel blood received from an atrium towards the peripheral beds within the body and lungs. The Atria primes the Pump...
moving left of center (the ultimate location of the heart) and the atria moving towards the head.
On day 28, areas of tissue in the heart tube begin to expand inwards; after about two weeks, these expansions, the membranous "septum primum
Septum primum
In the developing heart, the cavity of the primitive atrium becomes subdivided into right and left chambers by a septum, the septum primum, which grows downward into the cavity. The increasingly smaller gap below it is known as the ostium primum...
" and the muscular "endocardial cushions
Endocardial cushions
Atrioventricular cushions or endocardial cushions refers to a subset of cells in the primordial heart that play a vital role in proper heart septation.They develop on the atrioventricular canal.During development the heart starts out as a tube...
", fuse to form the four heart chambers of the heart. A failure to fuse properly will result in a defect that may allow blood to leak between chambers. After this happens, cells which have migrated from the neural crest begin to divide the bulbus cordis
Bulbus cordis
The bulbus cordis lies ventral to the primitive ventricle after the developing heart assumes its S-shaped form...
, the main outflow tract is divided in two by the growth a spiraling septum, becoming the great vessels—the ascending segment of the aorta and the pulmonary trunk. If the separation is incomplete, the result is a "persistent truncus arteriosis". The vessels may be reversed ("transposition of the great vessels
Transposition of the great vessels
Transposition of the great vessels is a group of congenital heart defects involving an abnormal spatial arrangement of any of the primary blood vessels: superior and/or inferior vena cavae , pulmonary artery, pulmonary veins, and aorta...
"). The two halves of the split tract must migrate into the correct positions over the appropriate ventricles. A failure may result in some blood flowing into the wrong vessel (e.g. overriding aorta
Overriding aorta
An overriding aorta is a congenital heart defect where the aorta is positioned directly over a ventricular septal defect, instead of over the left ventricle....
). The four chambered heart and the great vessels have features required for fetal growth. The lungs are unexpanded and cannot accommodate the full circulatory volume. Two structures exist to shunt blood flow away from the lungs. Cells in part of the septum primum die creating a hole while muscle cells, the "septum secundum
Septum secundum
The septum secundum, semilunar in shape, grows downward from the upper wall of the atrium immediately to the right of the primary septum and ostium secundum....
", grow along the right atrial side the septum primum, except for one region, leaving a gap through which blood can pass from the right artium to the left atrium, the foramen ovale
Foramen ovale (heart)
In the fetal heart, the foramen ovale , also ostium secundum of Born or falx septi, allows blood to enter the left atrium from the right atrium. It is one of two fetal cardiac shunts, the other being the ductus arteriosus...
. A small vessel, the ductus arteriosus
Ductus arteriosus
In the developing fetus, the ductus arteriosus , also called the ductus Botalli, is a shunt connecting the pulmonary artery to the aortic arch. It allows most of the blood from the right ventricle to bypass the fetus's fluid-filled lungs. Upon closure at birth, it becomes the ligamentum arteriosum...
allows blood from the pulmonary artery
Pulmonary artery
The pulmonary arteries carry deoxygenated blood from the heart to the lungs. They are the only arteries that carry deoxygenated blood....
to pass to the aorta.
Changes at birth
The ductus arteriosus stays open because of circulating factors including prostaglandins. The foramen ovale stays open because of the flow of blood from the right atrium to the left atrium. As the lungs expand, blood flows easily through the lungs and the membranous portion of the foramen ovale (the septum primum) flops over the muscular portion (the septum secundum). If the closure is incomplete, the result is a patent foramen ovale. The two flaps may fuse, but many adults have a foramen ovale that stays closed only because of the pressure difference between the atria.Causes
The cause of congenital heart disease may be either genetic or environmental, but is usually a combination of both.Genetics
Most of the known causes of congenital heart disease are sporadic genetic changes, either focal mutations or deletion or addition of segments of DNA. Large chromosomal abnormalities such as trisomiesTrisomy
A trisomy is a type of polysomy in which there are three copies, instead of the normal two, of a particular chromosome. A trisomy is a type of aneuploidy .-Description and causes:...
21
Down syndrome
Down syndrome, or Down's syndrome, trisomy 21, is a chromosomal condition caused by the presence of all or part of an extra 21st chromosome. It is named after John Langdon Down, the British physician who described the syndrome in 1866. The condition was clinically described earlier in the 19th...
, 13, and 18 cause about 5-8% of cases of CHD, with trisomy 21 being the most common genetic cause. Small chromosomal abnormalities also frequently lead to congenital heart disease, and examples include microdeletion of the long arm of chromosome 22 (22q11, DiGeorge syndrome
DiGeorge syndrome
22q11.2 deletion syndrome, which has several presentations including DiGeorge syndrome , DiGeorge anomaly, velo-cardio-facial syndrome, Shprintzen syndrome, conotruncal anomaly face syndrome, Strong syndrome, congenital thymic aplasia, and thymic hypoplasia is a syndrome caused by the deletion of a...
), the long arm of chromosome 1 (1q21), the short arm of chromosome 8 (8p23) and many other, less recurrent regions of the genome, as shown by high resolution genome-wide screening (Array comparative genomic hybridization
Array comparative genomic hybridization
Array-comparative genomic hybridization is a technique to detect genomic copy number variations at a higher resolution level than chromosome-based comparative genomic hybridization .-Process:DNA from...
).
The genes regulating the complex developmental sequence have only been partly elucidated. Some genes are associated with specific defects. A number of genes have been associated with cardiac manifestations. Mutations of a heart muscle protein, α-myosin heavy chain (MYH6
MYH6
Myosin-6 is a protein that in humans is encoded by the MYH6 gene.- Function :Cardiac muscle myosin is a hexamer consisting of two heavy chain subunits, two light chain subunits, and two regulatory subunits. This gene encodes the alpha heavy chain subunit of cardiac myosin...
) are associated with atrial septal defects. Several proteins that interact with MYH6 are also associated with cardiac defects. The transcription factor GATA4
GATA4
Transcription factor GATA-4 is a protein that in humans is encoded by the GATA4 gene.-Interactions:GATA4 has been shown to interact with NKX2-5, TBX5, ZFPM2, Serum response factor and HAND2.HDAC2- External links :...
forms a complex with the TBX5 which interacts with MYH6. Another factor, the homeobox
Homeobox
A homeobox is a DNA sequence found within genes that are involved in the regulation of patterns of anatomical development in animals, fungi and plants.- Discovery :...
(developmental) gene, NKX2-5
NKX2-5
Homeobox protein Nkx-2.5 is a protein that in humans is encoded by the NKX2-5 gene.-Interactions:NKX2-5 has been shown to interact with GATA4 and TBX5....
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
Holt-Oram syndrome
Holt–Oram syndrome is a disorder that affects bones in the arms and hands and may also cause heart problems.-Presentation:All people with this disorder have at least one limb abnormality that affects bones in the wrist . Often, these wrist bone abnormalities can be detected only by X-ray...
which includes electrical conduction defects and abnormalities of the upper limb. Another T-box gene, TBX1
TBX1
TBX1 is a human gene that codes for the protein called T-box 1. Genes in the T-box family play important roles in the formation of tissues and organs during embryonic development. To carry out these roles, proteins made by this gene family bind to specific areas of DNA. By attaching to critical...
, is involved in velo-cardio-facial syndrome DiGeorge syndrome
DiGeorge syndrome
22q11.2 deletion syndrome, which has several presentations including DiGeorge syndrome , DiGeorge anomaly, velo-cardio-facial syndrome, Shprintzen syndrome, conotruncal anomaly face syndrome, Strong syndrome, congenital thymic aplasia, and thymic hypoplasia is a syndrome caused by the deletion of a...
, the most common deletion which has extensive symptoms including defects of the cardiac outflow tract including tetralogy of Fallot
Tetralogy of Fallot
Tetralogy of Fallot is a congenital heart defect which is classically understood to involve four anatomical abnormalities...
.
| MYH6 | GATA4 | NKX2-5 | TBX5 | TBX1 | ||
|---|---|---|---|---|---|---|
| Locus Locus (genetics) In the fields of genetics and genetic computation, a locus is the specific location of a gene or DNA sequence on a chromosome. A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map... |
14q11.2-q13 | 8p23.1-p22 | 5q34 | 12q24.1 | 22q11.2 | |
| Syndrome Syndrome In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others... |
Holt-Oram Holt-Oram syndrome Holt–Oram syndrome is a disorder that affects bones in the arms and hands and may also cause heart problems.-Presentation:All people with this disorder have at least one limb abnormality that affects bones in the wrist . Often, these wrist bone abnormalities can be detected only by X-ray... |
DiGeorge DiGeorge syndrome 22q11.2 deletion syndrome, which has several presentations including DiGeorge syndrome , DiGeorge anomaly, velo-cardio-facial syndrome, Shprintzen syndrome, conotruncal anomaly face syndrome, Strong syndrome, congenital thymic aplasia, and thymic hypoplasia is a syndrome caused by the deletion of a... |
||||
| Atrial septal defects | ||||||
| Ventricular septal defects | ||||||
| Electrical conduction abnormalities | ||||||
| Outflow tract abnormalities | ||||||
| Non-cardiac manifestations | Upper limb abnormalities | Small or absent thymus Thymus The thymus is a specialized organ of the immune system. The thymus produces and "educates" T-lymphocytes , which are critical cells of the adaptive immune system.... Small or absent parathyroids Parathyroid gland The parathyroid glands are small endocrine glands in the neck that produce parathyroid hormone. Humans usually have four parathyroid glands, which are usually located on the rear surface of the thyroid gland, or, in rare cases, within the thyroid gland itself or in the chest... 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
JAG1
JAG1 is a protein associated with Alagille syndrome. JAG1 has also been designated as CD339 .-External links:* *...
, are identified in the majority of examined cases of arteriohepatic dysplasia (Alagille syndrome
Alagille syndrome
Alagille syndrome is a genetic disorder that affects the liver, heart, kidney, and other systems of the body. Problems associated with the disorder generally become evident in infancy or early childhood...
), characterized by defects of the great vessels (pulmonary artery stenosis), heart (tetralogy of Fallot
Tetralogy of Fallot
Tetralogy of Fallot is a congenital heart defect which is classically understood to involve four anatomical abnormalities...
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
NOTCH2
Neurogenic locus notch homolog protein 2 also known as notch 2 is a protein that in humans is encoded by the NOTCH2 gene.NOTCH2 is associated with Alagille syndrome and Hajdu–Cheney syndrome.- Function :Notch 2 a member of the notch family...
gene. In 10% of cases, no mutation is found in either gene. For another member of the gene family
Gene family
A gene family is a set of several similar genes, formed by duplication of a single original gene, and generally with similar biochemical functions...
, mutations in the Notch1
NOTCH1
Notch homolog 1, translocation-associated , also known as NOTCH1, is a human gene encoding a single-pass transmembrane receptor.A deficiency can be associated with bicuspid aortic valve....
gene are associated with bicuspid aortic valve
Bicuspid aortic valve
A bicuspid aortic valve is most commonly a congenital condition of the aortic valve where two of the aortic valvular leaflets fuse during development resulting in a valve that is bicuspid instead of the normal tricuspid configuration. Normally the only cardiac valve that is bicuspid is the mitral...
, 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.
Mutation of a cell regulatory mechanism, the Ras
Noonan syndrome
Noonan Syndrome is a relatively common autosomal dominant congenital disorder considered to be a type of dwarfism, that affects both males and females equally. It used to be referred to as the male version of Turner's syndrome ; however, the genetic causes of Noonan syndrome and Turner syndrome...
, LEOPARD syndrome
Leopard syndrome
LEOPARD syndrome - is part of a group called Ras/MAPK pathway syndromes - is a rare autosomal dominant, multisystem disease caused by a...
, Costello syndrome
Costello syndrome
Costello syndrome, also called faciocutaneoskeletal syndrome or FCS syndrome, is a rare genetic disorder that affects many parts of the body. It is characterized by delayed development and mental retardation, distinctive facial features, unusually flexible joints, and loose folds of extra skin,...
and cardiofaciocutaneous syndrome
Cardiofaciocutaneous syndrome
Cardiofaciocutaneous Syndrome is an extremely rare and serious genetic disorder.It is characterized by the following:*Distinctive facial appearance*Unusually sparse, brittle, curly scalp hair...
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.
Environmental
Known antenatal environmental factors include maternal infectionInfection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
s (Rubella
Rubella
Rubella, commonly known as German measles, is a disease caused by the rubella virus. The name "rubella" is derived from the Latin, meaning little red. Rubella is also known as German measles because the disease was first described by German physicians in the mid-eighteenth century. This disease is...
), drugs
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
(alcohol
Alcoholic beverage
An alcoholic beverage is a drink containing ethanol, commonly known as alcohol. Alcoholic beverages are divided into three general classes: beers, wines, and spirits. They are legally consumed in most countries, and over 100 countries have laws regulating their production, sale, and consumption...
, hydantoin
Hydantoin
Hydantoin, which is also known as glycolylurea, is a heterocyclic organic compound that can be thought of as a cyclic "double-condensation reaction" product of glycolic acid and urea...
, lithium
Lithium
Lithium is a soft, silver-white metal that belongs to the alkali metal group of chemical elements. It is represented by the symbol Li, and it has the atomic number 3. Under standard conditions it is the lightest metal and the least dense solid element. Like all alkali metals, lithium is highly...
and thalidomide
Thalidomide
Thalidomide was introduced as a sedative drug in the late 1950s that was typically used to cure morning sickness. In 1961, it was withdrawn due to teratogenicity and neuropathy. There is now a growing clinical interest in thalidomide, and it is introduced as an immunomodulatory agent used...
) and maternal illness (diabetes mellitus
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
, phenylketonuria
Phenylketonuria
Phenylketonuria is an autosomal recessive metabolic genetic disorder characterized by a mutation in the gene for the hepatic enzyme phenylalanine hydroxylase , rendering it nonfunctional. This enzyme is necessary to metabolize the amino acid phenylalanine to the amino acid tyrosine...
, and systemic lupus erythematosus
Lupus erythematosus
Lupus erythematosus is a category for a collection of diseases with similar underlying problems with immunity . Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, and lungs...
).
Prepregnancy and Maternal Obesity
As noted in several studies following similar body mass index (BMI) ranges, prepregnant and gestating women, who were obese (BMI ≥ 30), carried a statistically significant risk of birthing children with congenital heart defects (CHD) compared to normal-weight women (BMI= 19-24.9). Although there are minor conflicting reports, there was significant support for the risk of fetal CHD development in overweight mothers (BMI= 25-29.9). Additionally, as maternal obesity increased, the risk of heart defects did too indicating a trend between BMI and CHD odds. Altogether, these results present reasonable concern for women to achieve a normal-weight BMI prior to pregnancy to help decrease risk for fetal heart defects.A distinct physiological mechanism has not been identified to explain the link between maternal obesity and CHD, but both prepregnancy folate deficiency and diabetes have been implicated in some studies. Identification of the mechanism could aid health officials to develop reduction strategies and curb CHD’s prevalence in this preventable situation.
Classification
A number of differing classification systems exist for congenital heart defects. In 2000 the International Congenital Heart Surgery Nomenclature was developed to provide a generic classification system.Hypoplasia
HypoplasiaHypoplasia
Hypoplasia is underdevelopment or incomplete development of a tissue or organ. Although the term is not always used precisely, it properly refers to an inadequate or below-normal number of cells. Hypoplasia is similar to aplasia, but less severe. It is technically not the opposite of hyperplasia...
can affect the heart, typically resulting in the underdevelopment of the right ventricle
Right ventricle
The right ventricle is one of four chambers in the human heart. It receives deoxygenated blood from the right atrium via the tricuspid valve, and pumps it into the pulmonary artery via the pulmonary valve and pulmonary trunk....
or the left ventricle
Left ventricle
The left ventricle is one of four chambers in the human heart. It receives oxygenated blood from the left atrium via the mitral valve, and pumps it into the aorta via the aortic valve.-Shape:...
. This results in only one side of the heart capable of pumping blood to the body and lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
s effectively. Hypoplasia of the heart is rare but is the most serious form of CHD. It is called hypoplastic left heart syndrome
Hypoplastic left heart syndrome
Hypoplastic left heart syndrome , is a rare congenital heart defect in which the left ventricle of the heart is severely underdeveloped.-Causes:...
when it affects the left side of the heart and hypoplastic right heart syndrome
Hypoplastic right heart syndrome
Hypoplastic right heart syndrome is a condition where the right atrium and right ventricle are underdeveloped.It is less common than hypoplastic left heart syndrome.In some cases it can be identified prenatally.It can be associated with aortic stenosis....
when it affects the right side of the heart. In both conditions, the presence of a patent ductus arteriosus
Patent ductus arteriosus
Patent ductus arteriosus is a congenital disorder in the heart wherein a neonate's ductus arteriosus fails to close after birth. Early symptoms are uncommon, but in the first year of life include increased work of breathing and poor weight gain...
(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
Cyanotic heart defect
A cyanotic heart defect is a group-type of congenital heart defects . The patient appears blue , due to deoxygenated blood bypassing the lungs and entering the systemic circulation...
.
Obstruction defects
Obstruction defects occur when heart valves, arteries, or veins are abnormally narrowStenosis
A stenosis is an abnormal narrowing in a blood vessel or other tubular organ or structure.It is also sometimes called a stricture ....
or blocked
Atresia
Atresia is a condition in which a body orifice or passage in the body is abnormally closed or absent.Examples of atresia include:* Imperforate anus - malformation of the opening between the rectum and anus....
. Common defects include pulmonic stenosis
Pulmonic stenosis
Pulmonic stenosis, also known as Pulmonary stenosis, is a dynamic or fixed obstruction to flow from the right ventricle of the heart to the pulmonary artery. It is usually first diagnosed in childhood....
, aortic stenosis, and coarctation of the aorta
Aortic coarctation
Coarctation of the aorta, or aortic coarctation, is a congenital condition whereby the aorta narrows in the area where the ductus arteriosus inserts.-Types:There are three types:...
, 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
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
.
Septal defects
The septum is a wall of tissue which separates the left heartLeft heart
Left heart is a term used to refer collectively to the left atrium and left ventricle of the heart; occasionally, this term is intended to reference the left atrium, left ventricle, and the aorta collectively....
from the right heart
Right heart
Right heart is a term used to refer collectively to the right atrium and right ventricle of the heart; occasionally, this term is intended to reference the right atrium, right ventricle, and the pulmonary trunk collectively....
. Defects in the interatrial septum
Interatrial septum
The interatrial septum is the wall of tissue that separates the right and left atria of the heart.-Development:The interatrial septum forms during the first and second months of fetal development. Formation of the septum occurs in several stages...
or the interventricular septum
Interventricular septum
Interventricular septum , abbreviated IVS, is the stout wall separating the lower chambers of the heart from one another....
allow blood to flow from the left side of the heart to the right, reducing the heart's efficiency. Ventricular septal defect
Ventricular septal defect
A ventricular septal defect is a defect in the ventricular septum, the wall dividing the left and right ventricles of the heart.The ventricular septum consists of an inferior muscular and superior membranous portion and is extensively innervated with conducting cardiomyocytes.The membranous...
s are collectively the most common type of CHD, although approximately 30% of adults have a type of atrial septal defect
Atrial septal defect
Atrial septal defect is a form of congenital heart defect that enables blood flow between the left and right atria via the interatrial septum. The interatrial septum is the tissue that divides the right and left atria...
called probe patent foramen ovale.
Cyanotic defects
Cyanotic heart defectCyanotic heart defect
A cyanotic heart defect is a group-type of congenital heart defects . The patient appears blue , due to deoxygenated blood bypassing the lungs and entering the systemic circulation...
s are called such because they result in cyanosis
Cyanosis
Cyanosis is the appearance of a blue or purple coloration of the skin or mucous membranes due to the tissues near the skin surface being low on oxygen. The onset of cyanosis is 2.5 g/dL of deoxyhemoglobin. The bluish color is more readily apparent in those with high hemoglobin counts than it is...
, a bluish-grey discoloration of the skin due to a lack of oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
in the body. Such defects include persistent truncus arteriosus
Persistent truncus arteriosus
Persistent truncus arteriosus , also known as Common arterial trunk, is a rare form of congenital heart disease that presents at birth...
, total anomalous pulmonary venous connection
Total anomalous pulmonary venous connection
Total anomalous pulmonary venous connection , also known as total anomalous pulmonary venous drainage and total anomalous pulmonary venous return , is a rare cyanotic congenital heart defect in which all four pulmonary veins are malpositioned and make anomalous connections to the systemic venous...
, tetralogy of Fallot
Tetralogy of Fallot
Tetralogy of Fallot is a congenital heart defect which is classically understood to involve four anatomical abnormalities...
, transposition of the great vessels
Transposition of the great vessels
Transposition of the great vessels is a group of congenital heart defects involving an abnormal spatial arrangement of any of the primary blood vessels: superior and/or inferior vena cavae , pulmonary artery, pulmonary veins, and aorta...
, and tricuspid atresia
Tricuspid atresia
Tricuspid atresia is a form of congenital heart disease whereby there is a complete absence of the tricuspid valve. Therefore, there is an absence of right atrioventricular connection. This leads to a hypoplastic or absent right ventricle....
.
Defects
- Aortic stenosis
- Atrial septal defectAtrial septal defectAtrial septal defect is a form of congenital heart defect that enables blood flow between the left and right atria via the interatrial septum. The interatrial septum is the tissue that divides the right and left atria...
(ASD) - Atrioventricular septal defectAtrioventricular septal defectAtrioventricular septal defect or atrioventricular canal defect , previously known as "common atrioventricular canal" or "endocardial cushion defect", is characterized by a deficiency of the atrioventricular septum of the heart...
(AVSD) - Bicuspid aortic valveBicuspid aortic valveA bicuspid aortic valve is most commonly a congenital condition of the aortic valve where two of the aortic valvular leaflets fuse during development resulting in a valve that is bicuspid instead of the normal tricuspid configuration. Normally the only cardiac valve that is bicuspid is the mitral...
- DextrocardiaDextrocardiaDextrocardia is a congenital defect in which the heart is situated on the right side of the body. There are two main types of dextrocardia: dextrocardia of embryonic arrest and dextrocardia situs inversus...
- Double inlet left ventricleDouble inlet left ventricleA double inlet left ventricle is a congenital heart defect where both the left atrium and the right atrium feed into the left ventricle. Usually a hypoplastic right ventricle also exists...
(DILV) - Double outlet right ventricleDouble outlet right ventricleDouble outlet right ventricle is a form of congenital heart disease where both of the great arteries connect to the right ventricle...
(DORV) - Ebstein's anomalyEbstein's anomalyEbstein anomaly is a congenital heart defect in which the opening of the tricuspid valve is displaced towards the apex of the right ventricle of the heart.-Presentation:...
- Hypoplastic left heart syndromeHypoplastic left heart syndromeHypoplastic left heart syndrome , is a rare congenital heart defect in which the left ventricle of the heart is severely underdeveloped.-Causes:...
(HLHS) - Hypoplastic right heart syndromeHypoplastic right heart syndromeHypoplastic right heart syndrome is a condition where the right atrium and right ventricle are underdeveloped.It is less common than hypoplastic left heart syndrome.In some cases it can be identified prenatally.It can be associated with aortic stenosis....
(HRHS) - Mitral stenosisMitral stenosisMitral stenosis is a valvular heart disease characterized by the narrowing of the orifice of the mitral valve of the heart.-Signs and symptoms:Symptoms of mitral stenosis include:...
- Pulmonary atresiaPulmonary atresiaPulmonary atresia is a congenital malformation of the pulmonary valve in which the valve orifice fails to develop. The valve is completely closed thereby obstructing the outflow of blood from the heart to the lungs. The pulmonary valve is located on the right side of the heart between the right...
- Pulmonary stenosis
- Transposition of the great vesselsTransposition of the great vesselsTransposition of the great vessels is a group of congenital heart defects involving an abnormal spatial arrangement of any of the primary blood vessels: superior and/or inferior vena cavae , pulmonary artery, pulmonary veins, and aorta...
- dextro-Transposition of the great arteriesDextro-Transposition of the great arteriesdextro-Transposition of the great arteries , sometimes also referred to as complete transposition of the great arteries, is a birth defect in the large arteries of the heart...
(d-TGA) - levo-Transposition of the great arteriesLevo-Transposition of the great arterieslevo-Transposition of the great arteries , also commonly referred to as congenitally corrected transposition of the great arteries , is an acyanotic congenital heart defect in which the primary arteries are transposed, with the aorta anterior and to...
(l-TGA)
- dextro-Transposition of the great arteries
- Tricuspid atresiaTricuspid atresiaTricuspid atresia is a form of congenital heart disease whereby there is a complete absence of the tricuspid valve. Therefore, there is an absence of right atrioventricular connection. This leads to a hypoplastic or absent right ventricle....
- Persistent truncus arteriosusPersistent truncus arteriosusPersistent truncus arteriosus , also known as Common arterial trunk, is a rare form of congenital heart disease that presents at birth...
- Ventricular septal defectVentricular septal defectA ventricular septal defect is a defect in the ventricular septum, the wall dividing the left and right ventricles of the heart.The ventricular septum consists of an inferior muscular and superior membranous portion and is extensively innervated with conducting cardiomyocytes.The membranous...
(VSD)
Some conditions affect the great vessels or other vessels in close proximity to the heart, but not the heart itself, but are often classified as congenital heart defects.
- Coarctation of the aorta (CoA)
- Interrupted aortic archInterrupted aortic archInterrupted aortic arch is a very rare heart defect in which the aorta is not completely developed. There is a gap between the ascending and descending thoracic aorta. Almost all patients also have other cardiac anomalies. Interrupted aortic arch is often associated with DiGeorge...
(IAA) - Patent ductus arteriosusPatent ductus arteriosusPatent ductus arteriosus is a congenital disorder in the heart wherein a neonate's ductus arteriosus fails to close after birth. Early symptoms are uncommon, but in the first year of life include increased work of breathing and poor weight gain...
(PDA) - Scimitar syndromeScimitar syndromeScimitar syndrome, or pulmonary venolobar syndrome, is a rare congenital heart defect characterized by anomalous venous return from the right lung. This anomalous pulmonary venous return can be either partial or total...
(SS)- Partial anomalous pulmonary venous connectionPartial anomalous pulmonary venous connectionA Partial anomalous pulmonary venous connection is a congenital defect where right atrium is the point of return for the blood from some of the pulmonary veins.It is less severe than total anomalous pulmonary venous connection....
(PAPVC) - Total anomalous pulmonary venous connectionTotal anomalous pulmonary venous connectionTotal anomalous pulmonary venous connection , also known as total anomalous pulmonary venous drainage and total anomalous pulmonary venous return , is a rare cyanotic congenital heart defect in which all four pulmonary veins are malpositioned and make anomalous connections to the systemic venous...
(TAPVC)
- Partial anomalous pulmonary venous connection
Some constellations of multiple defects are commonly found together.
- tetralogy of FallotTetralogy of FallotTetralogy of Fallot is a congenital heart defect which is classically understood to involve four anatomical abnormalities...
(ToF) - pentalogy of CantrellPentalogy of CantrellPentalogy of Cantrell is a rare syndrome that causes defects involving the diaphragm, abdominal wall, pericardium, heart and lower sternum.It was characterized in 1958.An locus at Xq25-26 has been described....
- Shone's syndromeShone's syndromeShone's syndrome consists of a set of four cardiac defects: a supravalve mitral membrane , parachute mitral valve, subaortic stenosis and coarctation of the aorta. Essentially, it is both a left ventricular inflow and outflow obstruction...
/ Shone's complex / Shone's anomaly
Treatment
Sometimes CHD improves without treatment. Other defects are so small that they do not require any treatment. Most of the time CHD is serious and requires surgery and/or medications. Medications include diuretics, which aid the body in eliminating water, salts, and digoxin for strengthening the contraction of the heart. This slows the heartbeat and removes some fluid from tissues. Some defects require surgical procedures to restore circulation back to normal and in some cases, multiple surgeries are needed. Interventional cardiology now offers patients minimally invasive alternatives to surgery. Device closures can now be performed with a standard transcatheter procedure using a closure device mounted on a balloon catheter.Most patients require life-long specialized cardiac care, first with a pediatic cardiologist and later with and adult congenital cardiologist. There are more than 1.8 million adults living with congenital heart defects.
External links
- Cove Point Foundation Congenital Heart Disease website - comprehensive patient education, including animations of surgeries and interventions
- Congenital Heart Surgeons' Society Data Center - a research organization based at The Hospital for Sick Children, Toronto