1. What is Genetic Testing?
Genetic tests analyze DNA, which contains instructions for how an individual’s body develops and functions. Human DNA is almost identical from person to person regardless of factors such as gender, race, or ethnicity but some variability is present in each individual.
Many DNA sequence changes, called DNA variants, are common and benign (not harmful). However, some DNA variants may cause an individual to grow or develop differently and may impact health. Genetic tests can identify DNA variants and provide valuable insights into an individual’s health. The results may also provide information that is relevant to the health of family members.
GeneDX. Rapid Genome Testing for Neonatal & Pediatric Patients. PDF Resource. https://www.genedx.com/patient-support/
2. What Types of Changes Can Be Detected by Genetic Testing?
There are many different types of variants that can be identified in an individual’s DNA. These include changes to a single letter (nucleotide) , extra or missing pieces of DNA (duplications or deletions), or structural changes (translocations or inversions) where segments of DNA are rearranged. These changes can either be inherited from a parent or arise as new variants (referred to as de novo) in an egg or sperm cell.
Understanding the specific DNA variant and inheritance in complex medical cases may be crucial for confirming a diagnosis, determining treatment options and predicting health outcomes.
GeneDX. Rapid Genome Testing for Neonatal & Pediatric Patients. PDF Resource. https://www.genedx.com/patient-support/
3. Who Should be Tested? When Should They be Tested?
Exome or genome sequencing is recommended as a first-line test for anyone with unexplained epilepsy by the National Society of Genetic Counselors (NSGC), with endorsement from the American Epilepsy Society (AES). For individuals diagnosed with autism, the American Academy of Pediatrics (AAP) also recommends genetic testing
Detailed information is outlined in the AAP’s clinical report, “Genetic Evaluation of the Child With Intellectual Disability or Global Developmental Delay,” published in Pediatrics on June 23, 2025
The National Society of Genetic Counselors (NSGC) has issued a practice guideline, endorsed by the American Epilepsy Society (AES), which recommends genetic testing for any person with unexplained epilepsy, regardless of age at the time of testing or age at the time the seizures began. Specifically, the guideline recommends exome or genome sequencing as the first line test for unexplained epilepsy.
Smith L, Malinowski J, Ceulemans S, et al. Genetic testing and counseling for the unexplained epilepsies: An evidence-based practice guideline of the National Society of Genetic Counselors. J Genet Couns. Apr 2023;32(2):266-280. doi:10.1002/jgc4.1646
Taken together, we generated two clinical recommendations: ​
​(1) Genetic testing is strongly recommended for all individuals with unexplained epilepsy, without limitation of age, with exome/genome sequencing and/or a multi-gene panel (>25 genes) as first-tier testing followed by chromosomal microarray, with exome/genome sequencing conditionally recommended over multi-gene panel. ​
Smith L, Malinowski J, Ceulemans S, et al. Genetic testing and counseling for the unexplained epilepsies: An evidence-based practice guideline of the National Society of Genetic Counselors. J Genet Couns. Apr 2023;32(2):266-280. doi:10.1002/jgc4.1646
(2) It is strongly recommended that genetic tests be selected, ordered, and interpreted by a qualified healthcare provider in the setting of appropriate pre-test and post-test genetic counseling. Incorporation of genetic counselors into neurology practices and/or referral to genetics specialists are both useful models for supporting providers without genetics expertise to implement these recommendations.”
4. Why is Genetic Testing for Epilepsies Important?
Genetic testing for individuals with epilepsy may offer both clinical and personal benefit to patients and their families.
Clinically, genetic test results may lead to changes in an individual’s epilepsy treatment and management, including:
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initiation of precision treatments tailored to a person’s genetic information
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avoidance of contraindicated (could make a condition worse) treatments
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stopping unnecessary treatments and procedures
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providing information about recurrence risks in future pregnancies
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aiding in reproductive planning and allowing for prenatal diagnosis options for future pregnancies
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enabling genetic testing for at-risk family members
Smith L, Malinowski J, Ceulemans S, et al. Genetic testing and counseling for the unexplained epilepsies: An evidence-based practice guideline of the National Society of Genetic Counselors. J Genet Couns. Apr 2023;32(2):266-280. doi:10.1002/jgc4.1646
Smith L, Malinowski J, Ceulemans S, et al. Genetic testing and counseling for the unexplained epilepsies: An evidence-based practice guideline of the National Society of Genetic Counselors. J Genet Couns. Apr 2023;32(2):266-280. doi:10.1002/jgc4.1646
Smith L, Malinowski J, Ceulemans S, et al. Genetic testing and counseling for the unexplained epilepsies: An evidence-based practice guideline of the National Society of Genetic Counselors. J Genet Couns. Apr 2023;32(2):266-280. doi:10.1002/jgc4.1646
Smith L, Malinowski J, Ceulemans S, et al. Genetic testing and counseling for the unexplained epilepsies: An evidence-based practice guideline of the National Society of Genetic Counselors. J Genet Couns. Apr 2023;32(2):266-280. doi:10.1002/jgc4.1646
Smith L, Malinowski J, Ceulemans S, et al. Genetic testing and counseling for the unexplained epilepsies: An evidence-based practice guideline of the National Society of Genetic Counselors. J Genet Couns. Apr 2023;32(2):266-280. doi:10.1002/jgc4.1646
Genetic testing results may also provide important prognostic information which may influence palliative care (improving quality of life) decisions, impact hospitalization rates, enable referrals to specialty or multidisciplinary clinics, and influence research/clinical trial eligibility.
Smith L, Malinowski J, Ceulemans S, et al. Genetic testing and counseling for the unexplained epilepsies: An evidence-based practice guideline of the National Society of Genetic Counselors. J Genet Couns. Apr 2023;32(2):266-280. doi:10.1002/jgc4.1646
Finally, genetic test results may provide personal benefit to individuals and families. These may include :
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​Access to genetic counseling
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Accurate recurrence risk estimation for family members
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Availability of prenatal diagnosis and/or preimplantation genetic diagnosis
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Cascade testing of family members
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An end to the search for an answer (the “diagnostic odyssey”)
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Potential reduction of guilt/blame/shame
Importantly, a specific diagnosis may provide access to support organizations that connect families with the same genetic diagnosis.
Organizations such as the Rare Epilepsy Network (REN) contain a community of 150+ members and partners which provides opportunities for families to find gene/diagnosis-specific rare epilepsy organizations and gain information, education, support, research opportunities, and community.
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208/418 (49.8%) individuals with epilepsy who received a genetic diagnosis had clinical management changes
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125/167 (74.9%) with follow up had improved outcomes, typically decrease or elimination of seizures (108/167= 64.7%)
Utility of genetic testing for epilepsy observed in the publication Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice,
McKnight D, Morales A, Hatchell KE, et al. Genetic testing to inform epilepsy treatment management from an international study of clinical practice. JAMA Neurology. 2022;79(12):1267-1276.
Also D'Gama AM, Mulhern S, Sheidley BR, et al. (2023) Evaluation of the feasibility, diagnostic yield, and clinical utility of rapid genome sequencing in infantile epilepsy (Gene-STEPS): an international, multicentre, pilot cohort study. Lancet Neurol. Sep;22(9):812-825. PMID: 37596007 (showed almost 100% of individuals with clinical and/or persona utility); showed almost 100% of individuals with clinical and/or persona utility; Koh HY, Smith L, Wiltrout KN, Podury A, Chourasia N, D'Gama AM, Park M, Knight D, Sexton EL, Koh JJ, Oby B, Pinsky R, Shao DD, French CE, Shao W, Rockowitz S, Sliz P, Zhang B, Mahida S, Moufawad El Achkar C, Yuskaitis CJ, Olson HE, Sheidley BR, Poduri AH (2023) Utility of Exome Sequencing for Diagnosis in Unexplained Pediatric-Onset Epilepsy. JAMA Netw Open. Jul 3;6(7):e2324380. PMID: 37471090; PMCID: PMC10359957; Haviland I, Daniels CI, Greene CA, Drew J, Love-Nichols JA, Swanson LC, Smith L, Nie DA, Benke T, Sheidley BR, et al. (2023) Genetic Diagnosis Impacts Medical Management for Pediatric Epilepsies. Pediatr Neurol. 2023 Jan;138:71-80. PMID: 36403551; PMCID: PMC10099530.
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5. Why Should Genetic Testing be Done As Soon As Possible?
With epilepsy, there is a saying that “time is brain” and genetic testing results may have a direct effect on an individual’s medical care. A clinical workup for an individual with seizures commonly consists of an in-depth clinical intake and performing EEGs and MRIs. This is often followed by trying a single medicine or combination of anti-seizure medications (ASMs). These standards of care are valuable, but individuals and families should advocate for genetic testing to be included in an early workup. Although genetic testing is endorsed by professional medical societies, genetic testing is not always offered or accessible. See Section on Where to Find Genetic Testing.
NIH PubMed: From 2016 to 2020 study found from a child’s first seizure to when they underwent GT decreased from 3y to 8mo
Brock DC, Abbott M, Reed L, Kammeyer R, Gibbons M, Angione K, Bernard TJ, Gaskell A, Demarest S. Epilepsy panels in clinical practice: Yield, variants of uncertain significance, and treatment implications. Epilepsy Res. 2023 Jul;193:107167. doi: 10.1016/j.eplepsyres.2023.107167. Epub 2023 May 12. PMID: 37230012.
Dr. Tomi Pastinen created
an approach that provided
primary care clinicians of rural communities access to genetic testing which shortened time of diagnosis by 5.5mo, rather than the primary care team referring the patient to a specialist to recommend testing.
Salahi L. DNA Gains: Pediatricians Leverage Fast Genetic Testing for Neurodevelopmental Disorders. Medscape Medical News. Feb 2025. https://www.medscape.com/viewarticle/dna-gains-pediatricians-leverage-fast-genetic-testing-2025a10002px?form=fpf
Genetic testing early in the clinical workup has been shown to decrease the time to diagnosis, ending the diagnostic odyssey for up to 50% of individuals and families.
Salahi L. DNA Gains: Pediatricians Leverage Fast Genetic Testing for Neurodevelopmental Disorders. Medscape Medical News. Feb 2025. https://www.medscape.com/viewarticle/dna-gains-pediatricians-leverage-fast-genetic-testing-2025a10002px?form=fpf