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The proper development of the atrioventricular canal into its prospective components (The heart septum and associated valves) to create a clear division between the 4 compartments of the heart and ensure proper blood movement through the heart, are essential for proper heart function. When this process does not happen, a child will develop Atrioventricular Canal Defect which occurs in 2 out of every 10,000 births. It also has a correlation with Down Syndrome because 20% of children with Down Syndrome suffer from Atrioventricular Canal Disease as well. This is a very serious condition and surgery is necessary within the first 6 months of life for a child. Half of the children who are untreated with this conditon die during their first year due to heart failure of pnemonia.

Atrioventricular Canal Defect is a combination of abnormalities of the heart and is present at birth. There is a problem when there are holes present in the walls that seperate chambers (septum), as well as when valves are incorrectly constructed. There are other names for these heart abnormalities such as Endocardial Cushion Defect or Atrioventricular Septal Defect

Healthy Heart Overview

This a photo of the basic anatomical structures of the heart. Take note of how during "normal" heart development all four chambers are seperated and the mitral and tricupsid valves are properly developed.

In a normal healthy heart there are 4 chambers. This consists of right and left atria, and right and left ventricles. The Right atria and right ventricle's function is to pump blood to the lungs while the left atria and left ventricles pump blood to the rest of the body. There are valves in place that inhibit back-flow between these chambers.

Development of Atrioventricular Canal Disorder

This defect is developed because of the improper formation of the endocardial cushions, and their job is to separate the different parts of the heart during development. The structures that develop from the endocardial cushions are:

atrial septum- this structure divides the left and right atrium

ventricular septum-this structure divides the left and right ventricles.

Mitral Valve and Tricupsid valve- these valves are formed by the proper division of an early common valve being separated into two.

Types of AVCD

This is an echocardiography of "Complete" Atriventricular Canal Disorder. There is a clear absense of lower septum that would seperate all four chambers of the heart

There are 2 types of AVCD:

partial AVCD- includes openings between the left and right atria and improper formation of the mitral valve.

complete AVCD- there is free movement in all chambers because there is a large hole where the atria and ventricles meet, and instead of there being two valves there is one common valve.

Risk Factors

Down syndrome is often associated with AVCD, Having a parent with a congenital heart defect, alcohol use while pregnant, uncontrolled diabetes treatment during pregnancy and some medications during pregnancy.

A study also showed that there is also an increased risk of atrioventricular canal in patients who suffer from Noonan syndrome. The pattern seen in those patients with Noonan syndrome differ from those patients who have Down syndrome in that "partial" AVCD is more prevelant in those who suffer from NS, where as those who suffer from down syndrome show a prevelance of the "complete" form of AVCD.

Effects of Atrioventricular Canal Disorder

Complications

When there are holes in the septum that divide the 4 chambers of the heart the oxygen-rich blood and oxygen-poor blood mix this creates more stress on the heart to pump blood to where oxygen is needed. As a result, you get enlargement of the heart, heart failure (being unable to adequately supply body with needed oxygen, pulmonary hypertension, and pneumonia.

The development of pulmonary hypertension is very serious. And this because the left ventricle is weakened due to its overuse. When this happens, the pressure backs up into the pulmonary veins and the lungs. This type of damage is irreversible which is why immediate treatment is recommended after diagnosis.

Symptoms

Symptoms include difficulty breathing (dyspnea) and bluish discoloration on skin and lips (cyanosis). A newborn baby will show signs of heart failure such as edema, fatigue, wheezing, sweating and irregular heartbeat

Treatment

Surgery is usually conducted in-between the 3rd and 6th month of life, and with this condition the earlier the better. Usually, intracardiac repair is completed which is when they close the holes in the septum and they make two new atrioventricular valves that is available from the underdeveloped common valve leaflet.

Genetic Relationship

Tbx2 and its Effect on Proper Chamber Development

Example alt text

This picture shows how different individuals (homozygous positive +/+, heterozygous null +/-, or homozygous null -/- differ in the development of the heart.

Tbx2 is a T-box transcription factor and is usually expressed during various areas of embryogenesis. One notable expression is when it is shown in the development of the outflow system and atrioventricular canal of the developing heart.

In a study, they used targeted mutagenesis in mice to delete Tbx2 locus in some speciman. The results showed that mice who were homozygous and heterozygous null (+/+ & +/-) for Tbx2 resulted in the development of a healthier heart, while those who were homozygous null (-/-) for Tbx2 died early because of the inability of the heart to supply the body. It showed that there was insuffiecient formation of the endocardial cushion. There was a clear abnormality not only in the atrioventricular canal but also in the left ventricle. This study supports the fact that Tbx2 expression is important in the development of proper chamber differentiation, and in-turn cant have a direct relation to the development of Atrioventricular Canal Defect.