Genetics and Neurodevelopmental Disorders in CHD

A genetic disorder occurs when there are changes (also called variants) in DNA, which is your child’s unique genetic code. These changes can occur at different levels:

• in a single gene (monogenic),

• across multiple genes (polygenic), or

• involving missing, extra, or altered chromosomes (chromosomal disorders).

All chromosomal disorders are genetic disorders, but not all genetic disorders involve whole chromosomes. Examples include:

Single-gene disorders:

Sickle cell disease, Rett syndrome, Marfan syndrome, Neurofibromatosis type 1

Conditions influenced by multiple genes:

Asthma, diabetes, cleft lip/palate, autism, ADHD, dyslexia

Chromosomal conditions:

22q11.2 deletion syndrome (DiGeorge), Trisomy 21 (Down syndrome), Fragile X syndrome, Williams syndrome, Turner syndrome

DNA vs. Genes vs. Chromosomes: It Can Be Confusing!

Every cell in the human body contains a nucleus. Inside the nucleus are tiny, thread-like structures called chromosomes. Most people have 23 pairs (46 total) chromosomes—half inherited from each biological parent. Two of these chromosomes determine biological sex (XX or XY).

Each chromosome is made of a long strand of DNA, shaped like a twisted ladder (the double helix). Along the DNA are segments called genes, which provide instructions for how the body grows, develops, and functions. Humans have about 20,000 genes.

What Causes Genetic Variants?

Sometimes a genetic variant is inherited from a biological parent. Other times, it occurs spontaneously and is not inherited. Not all genetic variants lead to disease.

Some genetic conditions are associated with prenatal factors such as maternal diabetes, placental abnormalities, infections, some medications, alcohol or drug exposure, and others. However, in many cases, the cause of a genetic change is unknown.

A less obvious influence on how genes work is the environment, which includes physical exposures and life experiences. Factors such as pollution, nutrition, trauma, and chronic stress can affect how genes are expressed without changing the DNA itself. The field that studies this is called epigenetics.

How Genes Affect the Heart, Brain, and Development

Genes influence physical traits we can see (such as eye color), but they also guide the development and function of organs we cannot see—like the heart and brain. Scientists are making steady progress in understanding how combinations of genes contribute to congenital heart disease.

Neurodevelopmental and psychological conditions also have genetic influences. These include ADHD, speech and language disorders, learning disabilities (such as dyslexia), autism, schizophrenia, depression, and anxiety. Understanding family history can be very helpful when a child is showing developmental concerns.

Interestingly, many of the same genes are involved in multiple neurodevelopmental conditions. This helps explain:

• why symptoms overlap across diagnoses (for example, both ADHD and autism often involve attention and executive functioning challenges)

• why conditions commonly occur together (such as dyslexia and ADHD)

• and why diagnosis can sometimes be difficult or change over time

When Is Genetic Testing Considered?

Genetic testing is often pursued when a child has medical concerns that are known to occur in some genetic conditions, such as:

• intractable seizures

• congenital heart disease in certain contexts

• cleft lip or palate

• or other congenital anomalies

Testing may also be considered when a child has physical features suggestive of a genetic condition, such as specific facial features, differences in the ears, hands, feet, or skull shape.

Genetic testing does not always provide a clear answer, and it is not needed for every child with CHD. However, in some situations it can offer useful information to help guide care in a thoughtful and proactive way.

Most genetic testing is done using a blood sample or saliva (cheek swab). Testing may examine:

• a single gene

• whole chromosomes

• or a group of genes related to a specific concern (for example epilepsy or cleft lip/palate)

In some cases, these targeted tests are not enough to clarify a diagnosis.

Whole exome sequencing (WES) looks at all the protein-coding regions of genes, and whole genome sequencing (WGS) analyzes nearly all of a person’s DNA. These broader tests can provide a more comprehensive picture when answers are needed to guide treatment or long-term care. Standards for interpreting WES and WGS are still evolving, and some findings remain of uncertain significance.

When to Talk with Your Cardiologist About Genetic Testing

For a child with CHD, it may be helpful to talk with your cardiologist about genetic testing (such as WES or WGS) if any of the following are true—not because something is necessarily wrong, but because testing can sometimes clarify how best to support your child’s overall health and development:

• your child has significant developmental delays, autism, or learning differences that seem more than would be expected from their heart condition alone

• your child has seizures, abnormal movements, or other neurological concerns

• there are medical issues involving more than one body system, such as kidney, immune, endocrine, feeding, vision, or hearing problems

• your child’s developmental or medical course feels more complex or severe than anticipated, even after their heart condition has been addressed

• or your care team believes that identifying an underlying genetic condition could help guide medical monitoring, therapies, or long-term planning

Supporting Long-Term Development

If your child with CHD also has a genetic diagnosis, early identification of neurodevelopmental concerns is critical for timely intervention. Continued follow-up is equally important, since new challenges can emerge over time.

Developmental “transition points” are often periods of increased vulnerability, including:

• school readiness

• mid-elementary years (around 3rd–4th grade)

• early adolescence

• preparation for high school

• and planning after high school

Regular communication with your medical and school teams about your child’s learning, behavior, and emotional well-being helps ensure that supports remain appropriate as your child grows.