Genetic Testing and Congenital Heart Defects

Currently, 13 in every 1000 babies born alive have some sort of a heart defect. For approximately 1/3 of those babies, their heart defect could be explained through genetics right now. Every year scientists are able to find genetic causes for more and more cases of heart defects, as they discover more about the human genome and how it affects development.

Every person has multiple variations or “mutations” in DNA. Most of these mutations do not cause problems or illness. Sometimes, mutations in DNA do cause illness, and these are called “pathogenic” mutations. Some pathogenic gene variations only affect the heart. These are called “isolated” variations. Other times, pathogenic gene variations affect multiple organ systems. These are called “syndrome” variations.

Genetic information can vary in several ways, each of which can cause heart defects if the variations are pathogenic.  A heart defect might be caused by: 

• Single gene disorders: there is a mutation in a single gene

• Chromosome abnormalities: there are more or fewer chromosomes than is typical, or the structure of the chromosomes is different from usual

• Copy number variations (CNVs): sections of the genome repeat in an unusual way

Chromosome Analysis or Karyotyping looks at the chromosomes of DNA, which are like volumes of an encyclopedia. This kind of test can find large genetic differences, like when a chromosome is copied or missing, like in Down Syndrome or Edwards Syndrome. 

A Chromosomal Microarray looks at stretches of genes in each chromosome. This is like looking at all the chapter titles in all the volumes of an encyclopedia. This kind of test can find a copy number variant (CNV), which is when genes are duplicated or deleted in unusual ways.  

This kind of testing looks at genetic information that is similar to the chapter within one volume of an encyclopedia. This kind of test can detect when a portion of a chromosome is deleted, like in 22q11 Deletion Syndrome or Williams Syndrome.  

Single Gene Sequencing looks at all the base pairs in a single gene, which is like looking at all the letters in a single recipe of an encyclopedia. It is useful when doctors strongly suspect that a single gene may be causing a patient’s symptoms.  It can be used to detect syndromes such as Alagille Syndrome and Kabuki Syndrome. 

Familial Variant Testing examines a single base pair, which is like checking a single letter in a single recipe of an encyclopedia.  

Whole Exome Sequencing (WES) looks at all the base pairs in the genome, or all the letters in all the recipes of an encyclopedia.  It is helpful in finding uncommon gene differences that may be causing symptoms.  

Whole Genome Sequencing (WGS) is the most thorough kind of genetic testing. It examines every feature of the entire genome.  Using the example of an encyclopedia, WGS looks at every letter in every volume, plus the spacing, title page, footnotes, appendix, and table of contents. This kind of testing is not often used, since it is very slow and expensive, but it will be available more and more in the future.  

Sometimes people wonder why they might want to find a genetic cause of a heart defect.  They may not see how a genetic finding could affect a patient’s life or treatment.  However, doctors who specialize in the genetics of heart disease have discovered that genetic diagnoses can influence a patient’s life and treatment in important ways.   

Sometimes, a genetic diagnosis can help a care team to recognize a patient’s risk for illness in organ systems other than the heart.  For example, a genetic diagnosis might put a patient at risk for problems with their kidneys or their bones. 

When they know the genetic diagnosis, care teams can monitor and intervene as needed to help keep a patient’s whole body healthy.  Genetic diagnoses can even affect which medications or treatments are safe or effective for a particular patient. 

A genetic diagnosis often affects not just the patient, but the whole family.  Sometimes, other people in the family may carry the genes that cause the illness.  Family members may want to understand their own risk of developing an illness, and their risk of passing on an illness to their children.  The patient may also wonder how likely they are to pass on their illness to any future children.   

When a family receives a genetic diagnosis, they can also receive entrance into a community. Many of the genetic syndromes associated with heart defects have strong advocacy groups and support networks. For some families, learning a genetic diagnosis can open the door to invaluable social connections with people who really understand.