Factors Contributing to Congenital Heart Disease

What causes congenital heart disease?

A congenital heart defect (CHD) is a heart problem which is present at birth. It is caused by abnormal formation of the heart during fetal development. In most cases, when a baby is born with congenital heart disease, there is no known reason for it. Scientists know that some types of congenital heart defects can be related to an abnormality in the number of an infant's chromosomes, single gene defects, or environmental factors. In most cases, there is no identifiable cause for the heart defect, and they are generally considered to be caused by multifactorial inheritance.

Multifactorial inheritance means that "many factors" (multifactorial) are involved in causing a birth defect. The factors are usually both genetic and environmental, where a combination of genes from both parents, in addition to unknown environmental factors, combine to produce the trait or condition.

Maternal factors and CHD

Most mothers of babies born with congenital heart disease will look critically at their own behaviors during pregnancy to try to find a cause for their child's illness. It is important to remember that most cases of congenital heart disease have no known cause. However, some types of congenital heart defects are known to occur more often when the mother comes in contact with certain substances during the first few weeks of pregnancy, while the baby's heart is developing. Some maternal illnesses and medications taken for these illnesses have been shown to affect the heart's development. Other illnesses or medications seem to have no impact on the baby's heart. Always consult your health care provider or obstetrician for more information.

Women who have seizure disorders and need to take antiseizure medications may have a higher risk for having a child with congenital heart disease, as do women who take lithium to treat depression. Mothers who have phenylketonuria (PKU) who do not adhere to the special diet necessary to manage the disease during pregnancy have a higher risk of having a child with congenital heart disease. Also, women with insulin-dependent diabetes (particularly if the diabetes is not well-controlled) or lupus may have a higher risk of having a child with heart defects. Counseling is important for women with these chronic illnesses before becoming pregnant.

Rubella, a virus that most people in the United States were immunized against when they received the MMR vaccine, is known to cause birth defects. A woman who has never had rubella nor been vaccinated against the disease should consult her health care provider before becoming pregnant. A mother who contracts rubella during her pregnancy has a very significant chance of having a baby with birth defects, including congenital heart disease.

Always consult your health care provider before taking any medications while you are pregnant.

Family history and CHD

In the general population, about 1% of all children are born with congenital heart disease. However, the risk increases when either parent has CHD, or when another sibling was born with CHD.

Some heart defects are considered to have autosomal-dominant inheritance. This means that a parent with the defect has a 50% chance, with each pregnancy, to have a child with the same heart defect, and males and females are equally affected. Similarly, there is also a 50% chance that a baby will not be affected.

Consultation with a genetic counselor or genetic specialist is encouraged for women with congenital heart disease before becoming pregnant. In families with CHD either in the parents or prior children , fetal echocardiography can be done in the second trimester, at about 18 to 22 weeks of pregnancy, to look for the presence of major heart defects in the fetus.

Chromosome abnormalities and CHD

Chromosomes are the structures in your cells that contain your genes. Genes contain the code for your traits such as eye color and blood type. Usually, there are 46 chromosomes in each cell of the body. Having too many or too few chromosomes results in health problems and birth defects. Structural defects of the chromosomes, where a piece of a chromosome is missing, or present in duplicate, also cause health problems.

Problems with chromosomes that result in genetic syndromes, such as Down syndrome, often result in a higher incidence of infant heart malformations. Among infants with chromosome abnormalities, around 30% will have a heart defect. 

There are a number of chromosome abnormalities associated with congenital heart defects. Some of these include the following:

  • Down syndrome (trisomy 21)

  • Trisomy 18 and trisomy 13

  • Turner's syndrome

  • Cri-du-chat syndrome

  • Wolf-Hirshhorn syndrome

  • DiGeorge syndrome (22q11)

Chromosome analysis can be done from a small blood sample to look for a chromosome abnormality in a child with a congenital heart defect.

Single gene defects

There are an estimated 70,000 genes contained on the 46 chromosomes in each cell of the body. Genes come in pairs, one of which is inherited from the mother, the other from the father. Genes not only help to determine our individual traits, but also may be responsible for health problems when gene alterations (mutations) are present. When a single gene is mutated, a number of health problems may occur in a person. when several health problems occur from one genetic cause that is referred to as a syndrome. Some of the genetic syndromes associated with a higher incidence of heart defects include, but are not limited to, the following:

  • Marfan syndrome

  • Smith-Lemli-Opitz syndrome

  • Ellis-van Creveld syndrome

  • Holt-Oram syndrome

  • Noonan syndrome

  • Mucopolysaccharidoses

Other genetic syndromes that are not due to a single gene defect, but are associated with CHD, include Goldenhar syndrome (hemifacial microsomia), William's syndrome, and the VACTERL association (tracheal and esophageal malformations associated with vertebral, anorectal, cardiac, renal, and limb abnormalities.)

When a child is born with a congenital heart defect, if there is a suspicion that the child has some type of genetic syndrome, a doctor who specializes in genetics (called a clinical geneticist) may be asked to evaluate your child.

If a child has been diagnosed with a chromosomal or other genetic abnormality, genetic counseling is helpful to determine the risk for heart defects occurring in future children.