Heart Encyclopedia

Congenital Heart Disease, Contributing Factors

A congenital heart defect (CHD) is a heart problem that is present at birth, caused by improper development of the heart structure during fetal development (when the baby is forming in the mother's womb). Most of the time when a baby is born with congenital heart disease, there is no known reason for the heart to have formed improperly.

Scientists know that some types of congenital heart defects can be related to an abnormality of an infant's chromosomes (5 to 6%), single gene defects (3 to 5%) or environmental factors (2%). A genetic cause is more likely when there is a family history of CHD or if other health or learning differences are present.

In most cases, there is no identifiable cause for the heart defect. CHD is often considered to have a many contributing factors (multifactorial cause) that result in the defect of the heart. Multifactorial means that "many factors" are involved in causing a birth defect, not one main cause. The factors are usually both genetic and environmental, where a combination of genes from both parents, in addition to unknown environmental factors, produce the trait or condition.

Maternal Factors and CHD

Most mothers of babies born with CHD 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 CHD 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 doctor or obstetrician for more information.

Women who have seizure disorders and need to take anti-seizure medications may have a higher risk for having a child with CHD, as do women who take lithium to treat depression.

Mothers who have phenylketonuria (PKU) and do not adhere to the special diet necessary to manage the disease during pregnancy have a higher risk of having a child with CHD.

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 in order to take precautionary steps to reduce the risk of CHD.

Rubella, a virus that most people in the United States either had as a child or 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 physician 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 doctor before taking any medications while you are pregnant or think you could become pregnant.

Women who are pregnant with twins or multiples also have an increased chance of having a baby with a CHD.

Family History and CHD

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

Consider the following statistics for individuals without a known genetic cause:

• If you have had one child with congenital heart disease, there is a higher chance that another child will be born with CHD. This chance may range from 1.5 to 20%, depending on the type of CHD in the first child.
• If you have had two children with CHD, then the risk for having another child with CHD is higher.
• If the mother has CHD, the risk for a child to be born with CHD ranges from 2.5 to 18%, with an average risk of 6.7%.
• If the father has CHD, the risk for a child to be born with CHD ranges from 1.5 to 3%.
• Congenital heart defects involving obstructions to blood flow on the left side of the heart have a higher rate of occurring again within families than other heart defects.
• If another child is born with CHD, it can be a different type of defect than seen in the first child.
• In families with CHD either in the parents or children, fetal echocardiography can be performed (around 14-16 weeks, and again around 20 weeks) to determine the presence of major heart defects in the fetus.

Chromosome Abnormalities and CHD

Problems with chromosomes causing genetic syndromes, such as Down syndrome, often result in a higher incidence of infant heart malformations (CHD). About 5 to 8% of all babies with CHD have a chromosome abnormality.

Chromosomes are the structures in your cells that contain your genes; genes code for the traits that we see or observe 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, or extra or missing parts of chromosomes, results in health problems and birth defects.

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

• Down syndrome
• Trisomy 18 and trisomy 13 
• Turner syndrome
• Cri du chat syndrome
• Wolf-Hirshhorn syndrome
• DiGeorge syndrome (deletion 22q11)
• Williams syndrome

Single Gene Defects

There are an estimated 20,000 - 25,000 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 compose our individual traits but also compose health problems when gene alterations (mutations) are present. Single gene mutations can increase the risk for an isolated heart defect or can cause a genetic syndrome with a number of related health problems.

Several health problems linked to one genetic cause is often 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
• 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) and the VACTERL association (tracheal and esophageal malformations associated with vertebral, anorectal, cardiac, renal, radial and limb abnormalities make up the VACTERL syndrome).

There are a number of genes that are also known to cause what is referred to as non-syndromic CHD. These gene mutations can be passed down in families, but increase the risk for only CHD, without other health or learning problems. A number of genes are important in the normal development of the heart structure, and mutations in these genes are known to cause CHD. These genes include, but are not limited to the following:

• NOTCH1
• NKX2.5
• FLT4

Genetic testing—including chromosome analysis, chromosome microarray, and gene sequencing—can be performed from a small blood sample.

When a child is born or expected to be born with a congenital heart defect, meeting with a genetic counselor can help ensure the family can be fully informed, supported, and explore treatment options. A genetic counselor can review the medical and family history and discuss options for the timing (during the pregnancy or after the baby is born) and type of genetic testing. A genetic counselor can also share recommendations for heart screening in other family members, or future pregnancies, and discuss risk for CHD in future children. If there is a suspicion that the child has some type of genetic syndrome, a physician who specializes in genetics (called a clinical geneticist) may be asked to evaluate your child.