Congenital Heart Disease

From Biological Science (review) September 2013 volume 26 number 1

There are three main types of heat disease
1) Septation defects- Where the different areas of the heart do not separate properly from each other when the heart is formed

2) Unilateral Blocks- Defects of the heart valves

3) Routing Abnormalities - defects caused by failure to connect the main vessels that supply the heart with blood to the correct chambers of the heart.

It is estimated that between 1 and 5 % of the population suffers from structural or functional problems with the heart (known as congenital heart disease). This is caused by errors that happen when the baby's heart is forming in the womb, congenital heart problems are the most common birth defect and the leading cause of child death.
Many defects go unnoticed and some do not require treatment as a result it is very possible that the actual numbers of people with congenital heart problems is greater than the statistics suggest. The actual impact of the various problems vary, some can be diagnosed before birth with imaging technology some can be corrected with surgery while others are so server that the baby dies soon after being born.

The Mammalian Heart

In order to understand how congenital heart disease arises we must first understand how the heart develops.
During development the heart is transformed from a single tube to a four-chambered, muscular organ.

AS Recap

The heart has four chambers two atria and two ventricles
Blood leaves the heart to the body via the Aorta (oxygenated )
Blood reenters the heart via the Vena cava of which there is a superior and inferior vessel.(deoxygenated )
Blood returns to the heart form the longs via the pulmonary vien (oxygenated )
Blood leaves the heart to the lungs via the pulmonary artery (deoxygenated )

The walls of the left ventricle are stronger than that if the right this is because the left ventricle when it contracts has to pump blood all the way around the body whereas the right pumps blood only to the lungs.
The coronary blood vessels are the vessels that supply the heart mussels with the nutrients that they need such as oxygen and glucose for aerobic respiration.

The heart mussel is Myogenic- self stimulating.
Special structures such as the Sinoatrial node (SAN)  and the Atrioventricular node (AVN) regulate and control the rhythm that the heart beats.

 Heart Formation 

The heart is the first organ formed in the embryo and can start beating for as early as 22 days of gestation.
(Gestation is the carrying of an embryo or fetus inside female viviparous animals, including mammals, as well as some non-mammalian species. Mammals during pregnancy can have one or more gestations at the same time). 
The heart starts of as a crescent-shaped structure at about 2 weeks of gestation. This structure then transforms into a Y-shaped tube during which it will first start beating. 
The next stage of development - cardiac looping - which brings the different areas of the heart to their correct positions relative to one another. During cardiac looping the the heart tubes bend in a precise manner, this process is key and it is vital that each area of the heart is brought into the correct positions at the correct times.
Problems with this process can cause malfunctions in the heart which can disrupt or prevent later stages of development. Abnormalities at this stage can also prevent the correct attachment of blood vessels to the different chambers of the heart, leading to the previously mentioned Routing Abnormalities (meaning that the blood cannot flow through the heart properly).

After looping, chamber formation occurs. this process involves separating the atria and the ventricles from each other and connecting the growing heart  to the coronary blood vessels. This usually happens during weeks 6-8 of the pregnancy. It is during this period that the heart valves also develop if not developed properly then Unilateral blocks can come about. Other Malformations at this stage come usually in the form of 'holes in the heart' one such condition is a 'primary atrial septal defect' in other words a hole in the septum that divides the left and right atrial. Doctors can detect heart mummers by listening to the heart with a stethoscope where they should hear the irregular or unusual flow of blood through the heart. It is important to note that this is the most common type of heart disease and many people who have it do not even realize that they said defects. It is only when the individual reaches adult hood that it can become a problem when risk of pulmonary hypertension and stroke become greater. Larger holes can result in poor growth and lung problems in children.


The developing fetal heart also contains several specialised structures that are not present in the adult heart. One of these is the foramen ovale which is a small gap through which blood passes from the right atrium into the left atrium. This structure  is present in the fetus as it does not yet receive oxygen from its lungs but instead receives oxygenated blood from the placenta. The foramen ovale normally closes naturally after birth when the baby's hearts starts to pump blood around it whole body but in some cases it doesn't close possibly being asymptomatic (showing no symptoms) or otherwise needing corrective surgery. 

Genetic Investigation 

In order to understand why congenital heart disease occurs we must look at the genetics that control how the heart develops. Research scientists are currently looking at the effects of mutant DNA has on the development of the heart in order to discover which mutations cause specific heart defects.DNA can be thought as the instruction manual that controls how we are built, a fault in the final developmental of the heart can usually be tasted back to a fault in the DNA .

Forward And Reverse Genetics 

One method scientists are using to work out how the heart formation is regulated is called mutant screening. There are different ways that mutant screen investigations can be conducted.

1) Forward Genetics 

Involves studying individuals with certain characteristics of interest. The genetic sequences of individuals with selected characteristics (i.e. heart defects) are analysed to establish which gene or genes can cause the particular characteristic (for example a hole between the left and right atrial.

2) Reverse Genetics  

Reverse genetics involves examining the effect of a know gene on a specific characteristic. This leads o either the removing or mutating of a gene in mice to establish the impact that it has on heart development. 

Removing mutations has been used to establish the functions of several genes in heart development, for example knocking out a gene called Nkx2.5 in mice has been shown to disrupt the formation of the heart. Genetic study's in humans have shown that mutations in the Nkx2.5 gene is linked to atrial septal defects in some families.

Reverse genetics has allowed the identification of a gene responsible for several types of congenital heart disease in humans. The gene responsible is found on the 22nd chromosome and is the code for a protein called TBX1. Studies in mice have shown that this protein has significance in the early development of the heart.

Developments like this allow us to screen embryos for this mutation, making detection and treatment of congenital heart disease easier. It is hoped that one day it may be possible to intervene during the development of the fetus overriding or correcting the damaging  mutation, thus enabling the heart to developed normally.