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PubMed This is a summary of 21 peer-reviewed journal articles Updated
Neurology · Genetic Epilepsy with Febrile Seizures Plus

The Diagnostic Journey: Gathering the Evidence

At a Glance

GEFS+ is diagnosed by combining a child's seizure pattern, family history, clinical evaluation, and genetic testing. A normal early EEG or MRI does not rule it out, and an SCN1A variant alone does not establish Dravet syndrome.

Getting a diagnosis for Genetic Epilepsy with Febrile Seizures Plus (GEFS+) is rarely a single event. Instead, it is a process of gathering evidence from your family’s history, your child’s clinical symptoms, and advanced genetic testing [1]. Because the symptoms can change as a child grows, the diagnosis may evolve over time [2].

The Clinical Foundation: Your Story

The most important diagnostic tool is the clinical history. Your doctor will ask for a “pedigree”—a detailed family tree—to see if other relatives had childhood seizures, even if they were only mild “fever fits” [3][4]. Because GEFS+ has incomplete penetrance, family history alone cannot establish carrier status, but it provides vital context [1].

Genetic Testing: More Than Just SCN1A

While SCN1A is the most common gene involved, testing for just one gene is often not enough.

  • Epilepsy Panels: These tests look at hundreds of genes known to cause seizures simultaneously [5]. Panel testing should be selected with genetics professionals.
  • Exome or Genome Sequencing: These tests look at almost all of a child’s DNA [2]. This is often used if a panel comes back negative, as it can find rarer or “de novo” (new) mutations [6][7].

Important: Finding a mutation in the SCN1A gene does not automatically mean your child has Dravet syndrome [8]. SCN1A mutations cause a range of conditions, and many children with these variants have the much milder GEFS+ phenotype [9].

Why Early Tests Often Look “Normal”

It can be confusing and even frustrating when your child is having seizures but their brain scans and electrical tests come back normal. In the early stages of GEFS+, this is actually very common [10].

  • EEG (Electroencephalogram): This test records brain waves. In the first year of life, many children with GEFS+ or even early Dravet syndrome have a normal EEG [11][10]. A normal result does not rule out epilepsy, and there is no fixed schedule for repeating a normal EEG.
  • MRI (Magnetic Resonance Imaging): An MRI looks at the physical structure of the brain. In GEFS+, the brain’s structure is typically normal [12]. While an MRI is not routinely required for every child with a simple febrile seizure, it may be used to rule out other causes (like a tumor or injury) [13].

Your Genetic Report Checklist

When you receive your child’s genetic test results, ensure it includes these specific details. If any are missing, ask your neurologist or a genetic counselor to clarify:

  • Gene Name: (e.g., SCN1A, GABRG2)
  • Variant Nomenclature: This looks like a code (e.g., c.123G>A) and tells you exactly where the change is [14].
  • Zygosity: Usually “heterozygous,” meaning the child has one normal copy and one changed copy of the gene [15].
  • Classification: Is it Pathogenic (proven to cause disease), Likely Pathogenic, or a Variant of Uncertain Significance (VUS)? A VUS is an “inconclusive” result that needs more research [16][17]. A VUS should not be used by itself to diagnose GEFS+, guide medication, or make predictive decisions.
  • Inheritance Status: Did the test include the parents (Trio testing)? This tells you if the variant was inherited or is de novo (new to the child) [18][19]. Note that a negative parent blood test does not completely exclude parental mosaicism.
  • CNV Coverage: Did the lab check for large missing or extra pieces of the gene (called Copy Number Variants) [20][5]?

By keeping a thorough record of your child’s seizures and a copy of their full genetic report, you provide the “evidence” your care team needs to tailor their treatment plan [21].

Common questions in this guide

How is GEFS+ diagnosed?
GEFS+ is diagnosed by putting together the child's seizure history, family history, clinical pattern, and genetic test results; no single test confirms every case. The diagnosis may be refined as symptoms change with age.
Can a normal EEG rule out GEFS+?
Not necessarily. Many children with GEFS+ have a normal EEG early in life, especially during the first year, and a normal result does not rule out epilepsy. The neurologist can decide whether and when another EEG is useful.
What does a normal MRI mean when GEFS+ is suspected?
The brain structure is usually normal in GEFS+, so a normal MRI is common and does not by itself confirm or exclude the condition. MRI may be ordered to look for other causes, such as an injury or tumor, and it is not routinely needed for every child with a simple febrile seizure.
Does an SCN1A mutation mean my child has Dravet syndrome?
No. SCN1A changes are linked to a range of epilepsy conditions, including GEFS+ and Dravet syndrome. An SCN1A result must be interpreted alongside the child's seizure pattern, development, and other clinical information.
What does a VUS mean on an epilepsy genetic test?
A VUS, or variant of uncertain significance, is a genetic change that current evidence cannot clearly label as disease-causing or harmless. It should not be used by itself to diagnose GEFS+, choose medication, or make predictive decisions.
What information should be included in a GEFS+ genetic report?
Look for the gene name, the exact variant code, whether one or both gene copies are changed, the laboratory's classification, and whether the variant was inherited or new. The report should also say whether large missing or extra DNA segments were checked; these are called copy number variants.
Can GEFS+ run in families?
GEFS+ can occur in families, so a family history of childhood febrile seizures or other seizures is important. Testing both parents can show whether a variant was inherited or arose newly in the child, although a negative blood test in a parent does not completely rule out mosaicism, in which only some cells carry the variant.

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Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.How many genes were tested in the panel you ordered, and did it include a check for large deletions or duplications (Copy Number Variants)?
  2. 2.Given that the early EEG and MRI were normal, how often should we repeat these tests as my child gets older?
  3. 3.Can you explain why this specific genetic variant was classified as 'Likely Pathogenic' versus a 'Variant of Uncertain Significance'?
  4. 4.Does the genetic report show if this was a 'de novo' mutation or if it was inherited from one of us, and why does that matter for our other children?
  5. 5.Based on my child's seizure pattern and the genetic results, why do you believe this is GEFS+ rather than a different condition?

References

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This page is for informational purposes only and does not constitute medical advice. A pediatric neurologist and genetic counselor should interpret your child's GEFS+ results and guide care.