What is Genetic Testing
Overview
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/
Detectable Changes
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/
Who & When to Test
As understanding of the genetic basis of neurological and neurodevelopmental conditions has rapidly advanced, multiple professional medical societies now recommend genetic testing as part of standard care for individuals with unexplained epilepsy, autism spectrum disorder (ASD), and global developmental delay/intellectual disability (GDD/ID). These guidelines reflect a growing recognition that identifying an underlying genetic cause can directly impact diagnosis, treatment, medical management, prognosis, research access, and family planning.
Outlined below are each guideline, plus a summary, criteria, testing recommendations, goals of testing and rationale.
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
National Society of Genetic Counselors (endorsed by American Epilepsy Society)
American Academy of Pediatrics – Autism Spectrum Disorder (ASD)
American Academy of Pediatrics – Global Developmental Delay / Intellectual Disability (GDD/ID)
Summary
Recommends exome/genome sequencing for individuals with unexplained epilepsy.
Recommends genetic evaluation for children diagnosed with autism spectrum disorder.
Recommends genetic evaluation for children with unexplained global developmental delay or intellectual disability.
Who It Applies To
Individuals with:
• Infantile or childhood-onset epilepsy• Developmental and epileptic encephalopathies (DEEs)
• Epilepsy with autism, developmental delay, or intellectual disability
• Drug-resistant epilepsy
• Suspected genetic epilepsy syndromes
• Epilepsy without a clear acquired or structural cause
Children diagnosed with ASD, particularly when accompanied by:
• Intellectual disability
• Epilepsy/seizures
• Developmental delay
• Congenital anomalies
• Regression
• Strong family history
Children with unexplained:
• Global developmental delay
• Intellectual disability
• Neurodevelopmental concerns without a known cause
Testing Recommendations
Exome sequencing (ES) or genome sequencing (GS) recommended as first-line testing in many cases.
Historically recommended:
• Chromosomal microarray (CMA)
• Fragile X testing
Increasing use of ES/GS, especially when autism co-occurs with epilepsy or developmental concerns.
Updated guidance increasingly supports ES/GS as first-tier testing for many individuals with unexplained GDD/ID.
Goals of Testing
• Guide treatment choices
• Avoid ineffective medications
• Identify precision therapies or clinical trials
• Clarify prognosis• Inform recurrence risk/family planning
• Connect families to syndrome-specific resources and research
• Identify an underlying diagnosis
• Inform medical management
• Screen for associated health risks
• Clarify recurrence risk
• Connect families to supports and research opportunities
• Establish an underlying diagnosis
• Improve medical management and care coordination
• Reduce prolonged diagnostic odysseys
• Inform prognosis and recurrence risk
• Support access to services, research, and targeted therapies
Rationale
Many epilepsies are now understood to have a genetic basis, even when MRI or routine testing is normal.
Autism frequently has an identifiable biological or genetic contributor.
Developmental delay and intellectual disability often have an underlying genetic cause that may directly impact care and outcomes.
Why It Matters Now
Genetic testing for individuals with epilepsy may offer both clinical and personal benefits to patients and their families.
Clinically, genetic test results may lead to changes in an individual’s epilepsy treatment and management, including:
-
initiation of precision treatments tailored to a person’s genetic information
-
avoidance of contraindicated (could make a condition worse) treatments
-
stopping unnecessary treatments and procedures
-
providing information about recurrence risks in future pregnancies
-
aiding in reproductive planning and allowing for prenatal diagnosis options for future pregnancies
-
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 :
-
Access to genetic counseling
-
Accurate recurrence risk estimation for family members
-
Availability of prenatal diagnosis and/or preimplantation genetic diagnosis
-
Cascade testing of family members
-
An end to the search for an answer (the “diagnostic odyssey”)
-
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 hundreds of rare epilepsy organizations which provides opportunities for families to find gene/diagnosis-specific communities and gain information, education, research opportunities, and support.
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.
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
Genetic testing is recommended for people of all ages including adults. Genetic testing in adults has led to initiation of new medications, discontinuation of other medications, referrals to new specialists comorbidity monitoring, surgery, clinical trial access and other improvements. [Endnote: McKnight et al, JAMA Neuro 2022]
More information can be found at Genetic Epilepsy in Adults network (GEAN). Find clinicians specializing in adults with genetic epilepsies here. This resource also includes resources for practitioners and adults with epilepsies.
