Genetic Testing in LGS

What is genetic testing?

Genetic testing is a type of medical test that looks for changes, sometimes called mutations or variants, in your DNA. Genetic testing is useful and may change the medical care you or your family member receives. There are many different kinds of genetic tests. Genetic tests are done using a blood or saliva sample and results are usually ready in a few weeks to months. Because we share DNA with our family members, if a loved one is found to have a genetic change, other family members may have the same change. This is not always true. Some genetic changes may be unique to the person. Speaking to a genetic counselor can help you understand your genetic test.

Why is Genetic Testing in LGS Important?

Genetic testing for individuals with neurodevelopmental disabilities is underutilized in the United States and many people with an LGS diagnosis may not know about the opportunity for a genetic test or its impact. There has also been historical mistrust in the community about the intent of genetic research and genetic testing, and lingering concern about the use of genetic information, especially given the ubiquity of online platforms to store the data. We continue to urge scientists to listen to, carefully consider, and integrate solutions for the concerns of stakeholder communities to improve the process. The goal of genetic research is to expand the knowledge of the genetic underpinnings of human health to improve the quality of life for those with a genetic diagnosis.

 

Download the Genetics and LGS Information Sheet

For everyone with LGS, the LGS is secondary to some initial cause (etiology) of early-life seizures (e.g., LGS secondary to CDKL5 mutations). In half of LGS cases, the cause of seizures is genetic. Therefore, we recommend that all individuals with an LGS diagnosis, including biological parents, receive clinical genetic testing and feedback from a genetic counselor on their genetic results.

Anyone who does not know the cause of their seizures should talk to their doctor about genetic testing. It is NOT too late for adults with LGS to have testing and this may change treatment. A genetic test is not a substitute for a clinical evaluation, it is used to help understand the causes of that person’s diagnosis to possibly narrow down and target treatment and support opportunities.

Scientific research has identified numerous rare genetic conditions associated with LGS that explain and help understand and manage co-morbid conditions associated with LGS, personalize intervention and support options, and provide support to families through Patient Advocacy Groups.

Understanding your genetic makeup is critical to not just an LGS diagnosis but to your overall health. Additionally, one-quarter of those tested are found to have a genetic cause for their epilepsy. 12-50% of patients have their treatment changed when a genetic cause is found.

The first step should be to talk with your neurologist, pediatrician, or other health care professional (usually the one who made the LGS diagnosis in the first place) to obtain a prescription for a genetic test and then work with your insurance company to determine what, if anything, will be covered. Each plan and company has its guidelines on this.

Any genetic test should be followed by a meeting with a genetic counselor to discuss the results and identify genes that are known to be associated with autism, as well as gene mutations of unknown significance. We also urge families to contribute their data to genetic repositories where the analyses can be contributed to large studies investigating the role of different genes in different outcomes.

Types of Genetic Tests

There are many different types of tests, some compare the results to a set of genes that are known to be associated with LGS. Others use an approach where genes in addition to those already known to be associated with LGS are tested. We support the use of Whole Exome Sequencing as the most sensitive type of genetic analysis to identify actionable genetic variants in the genome.

Types of Genetic Tests

Single gene tests look for changes in only one gene. Single gene testing is done when your doctor believes you or your child have symptoms of a specific condition or syndrome. Some examples of this are Duchene muscular dystrophy or sickle cell disease. Single gene testing is also used when there is a known genetic mutation in a family.
A gene panel test looks for changes in many genes in one test. Genetic testing panels are usually grouped into categories based on different kinds of medical concerns. Some examples of genetic panel tests are low muscle tone, short stature, or epilepsy. Gene panel tests typically test anywhere between 100 to 1000 genes.
There are two different kinds of large-scale genetic tests.
  • Exome sequencing looks at all the genes in the DNA (whole exome) or just the genes that are related to medical conditions (clinical exome).
  • Genome sequencing is the largest genetic test and looks at all of a person’s DNA, not just the genes.
Exome and genome sequencing are ordered by doctors for people with complex medical histories. Large-scale genomic testing is also used in research to learn more about the genetic causes of conditions. Large-scale genetic tests can have findings unrelated to why the test was ordered in the first place (secondary findings). Examples of secondary findings are genes associated with a predisposition to cancer or rare heart conditions when you were looking for a genetic diagnosis to explain a child’s developmental disabilities.
Karyotype is a test to identify and evaluate the size, shape, and number of chromosomes in a sample of body cells. Extra or missing chromosomes, or abnormal positions of chromosome pieces, can cause problems with a person's growth, development, and body functions.
Chromosomal microarray analysis (CMA) is a technology used for the detection of clinically-significant microdeletions or duplications, with a high sensitivity for submicroscopic aberrations.
 
Chromosomal microarray (CMA) is increasingly utilized for genetic testing of individuals with unexplained developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), or multiple congenital anomalies (MCA).

Genetic Testing Resources

GeneDx offers tests for rare and ultra-rare genetic disorders and covers conditions related to neurology, hereditary cancer, cardiology, and more.

GeneDx offers services in over 55 countries and claims to be a global industry leader in genomics and genetic testing. GeneDx is a member of the iHope Whole Genome Sequencing Program, a philanthropic program that provides WGS at no cost to patients who cannot afford the tests.

Learn more at www.genedx.com

The overall goal of Project FIND-OUT is to facilitate early and accurate genetic diagnosis of rare genetic neurodevelopmental disorders in infants between the ages of 3-12 months in the United States.

Babies with feeding issues, problems with movement or muscle tone, or who have missed developmental milestones may benefit from genetic testing. Learn more about Project FIND-OUT, which provides free genetic counseling and testing for infants between the ages of 3-12 months, and whether your baby might be eligible, visit projectfindout.org

Invitae is a genetic testing company and its mission is to improve the quality of health care by offering high-quality, affordable genetic testing. Invitae offers several epilepsy panels including their Behind the Seizure program. This offers a no-cost, comprehensive epilepsy panel to any child under the age of 8 who has had an unprovoked seizure.

An epilepsy gene panel can bring you closer to understanding what’s causing your loved one’s seizures, helping patients and caregivers benefit from deeper knowledge and timely care. To learn more about the many epilepsy gene panels at Invitae including the Behind the Seizure program, visit www.invitae.com

The Rare Genomes Project (RGP) at the Broad Institute of MIT and Harvard is a patient-driven research study led by genomics experts and clinicians who believe that the latest advances in genomic sequencing are changing medicine and should be accessible to families with rare and undiagnosed conditions.

You may be eligible to participate in this research study aimed at discovering the genes underlying your loved one’s rare disease. If so, your loved one will receive whole genome sequencing at no cost to you.

If a genetic change is discovered that may be the underlying cause of your loved one’s LGS, the researchers will confirm it in a clinical lab and work with your doctor to return the result to you.

To learn more, visit the Rare Genomes Project at raregenomes.org

iHope™ Genetic Health is a program governed, managed, and operated by Genetic Alliance that will eliminate the barriers to genomic insights for tens of thousands of individuals across the globe each year.

Leveraging contributions of genomic sequencing technology from Illumina, Inc., and donations from philanthropists and technology partners, iHope™ Genetic Health will provide contract awards that enable genomic testing across the globe. Learn more about iHope™ Genetic Health at ihopegenetichealth.org

This free testing program applies to all people in the US (except New York) with symptoms suggestive of pediatric seizure disorders. People affected by these conditions may present with seizures, developmental delays, and abnormal muscle movements. Patients who submit to the program are reviewed on a case by case basis to determine their eligibility for a free genetic test.

Learn more at www.probablygenetic.com

Invitae’s mission is to make high-quality genetic testing affordable and accessible through every stage of life.

Invitae partners with other companies to offer sponsored, no-charge testing—and in some cases genetic counseling—for patients who meet eligibility criteria.

Learn more at www.invitae.com

Updated 10/18/24 (KK)