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PubMed This is a summary of 17 peer-reviewed journal articles Updated
Neurology

The Biology and Genetics of EEM

At a Glance

Epilepsy with eyelid myoclonia usually reflects a complex interaction of brain visual networks and many genetic factors, not one identifiable mutation. Genetic testing is mainly considered when developmental challenges, drug-resistant seizures, or a strong family history are present.

Understanding the “why” behind epilepsy with eyelid myoclonia (EEM) involves looking at both how the brain communicates in the moment and the genetic blueprint that built those connections. While most cases of EEM are not caused by a single identifiable gene mutation, research has made significant strides in uncovering the biological networks and genetic markers involved [1][2].

The Brain’s Visual Network

In EEM, the seizures do not stem from a structural brain lesion or damage. Instead, they involve an abnormal interaction within a proposed visual-cortical network model [3][4].

The brain has specific areas for processing vision (at the back, in the occipital lobe) and for controlling movement (the motor cortex). In children with EEM, these areas appear to be highly sensitive [5]. When the eyes close or see a flickering light, it activates this visual network. In this evolving scientific model, the signal spreads rapidly through the brain’s “wiring” (corticothalamic networks), leading to the generalized electrical discharge that causes the eyelids to flutter [3][6].

Is EEM Hereditary?

There is a strong familial susceptibility in EEM, meaning the tendency to have these seizures can run in families [7].

  • Family History: Between 32% and 47% of children in studied EEM cohorts have a relative with some form of epilepsy [7][8].
  • Complex Inheritance: For most families, EEM is likely “polygenic,” meaning it is caused by a combination of many small genetic variations rather than one single mutation [9][1]. This is why most children with EEM do not have a single identifiable “epilepsy gene” on standard tests [1].

When is Genetic Testing Recommended?

Most children with “isolated” EEM (meaning they have typical development and the seizures respond well to medication) do not need extensive genetic testing [1][2]. However, testing—such as an epilepsy gene panel or whole-exome sequencing (WES)—is generally considered in specific situations [2]:

  1. Developmental Challenges: If the child has an intellectual disability, autism, or significant developmental regression combined with epilepsy [1][10].
  2. Drug Resistance: If the seizures are severe and do not respond to standard anti-seizure medications [2].
  3. Family History: If there is a strong pattern of similar seizures across multiple generations [2].

In study cohorts of children who have both EEM and developmental challenges, the “diagnostic yield” (the chance of finding a specific genetic association) is about 28%, compared to only about 1% for children with isolated EEM [1]. A negative genetic test does not rule out the diagnosis of EEM, and many genetic results (such as a “variant of uncertain significance”) do not change the treatment plan.

Key Genes in Complex EEM

When EEM is part of a more complex picture—sometimes called a developmental and epileptic encephalopathy (DEE)—certain rare gene associations have been reported in studies:

  • CHD2: Occasionally linked to EEM when it occurs alongside intellectual disability, photosensitivity, and behavioral traits [1][10].
  • SYNGAP1: Associated with intellectual disability and a very high rate of eyelid myoclonia [11].
  • NEXMIF: A gene linked to a range of seizure types, including eyelid fluttering, especially in children with developmental delays [12][13].
  • RORB: Variants in this gene have been reported in individuals with a specific type of photosensitive epilepsy that looks very similar to EEM [14][15].

If your child’s doctor recommends genetic testing, they may also order a chromosomal microarray (CMA) to check for missing or extra pieces of DNA (called copy-number variations), as these can also be a cause of the syndrome [13][16]. Finding a specific genetic name doesn’t change the diagnosis of EEM, but genetic counseling is highly recommended to understand what the results mean for your family [17].

Common questions in this guide

What is thought to cause epilepsy with eyelid myoclonia?
EEM is not usually caused by a visible brain lesion or prior brain damage. Researchers think eye closure or flickering light activates an unusually sensitive visual network that can spread through connected brain circuits and trigger generalized seizure activity.
Does EEM run in families?
Yes, a family tendency is common, and many children with EEM have a relative with epilepsy. In most families, susceptibility involves many small genetic differences rather than one mutation found on a standard test. This does not mean that every relative will develop EEM.
When should a child with EEM have genetic testing?
Children with typical development and seizures that respond well to medicine often do not need extensive genetic testing. Doctors may consider an epilepsy gene panel or whole-exome sequencing when there are developmental or learning concerns, seizures that remain uncontrolled despite medicine, or a strong family pattern of epilepsy.
What kinds of genetic tests may be used for EEM?
Testing may include an epilepsy gene panel or whole-exome sequencing to look for changes in individual genes. A chromosomal microarray may also look for missing or extra pieces of DNA, called copy-number changes.
How often does genetic testing find an explanation for EEM?
The chance of finding a specific genetic association varies with a child's overall presentation. In study groups, a genetic explanation was found in about 1% of children with isolated EEM and about 28% of children with EEM and developmental challenges, so these figures cannot predict an individual result.
What does a negative or uncertain genetic result mean for my child's EEM?
A negative result does not rule out EEM because most cases are not caused by one identifiable gene change. A variant of uncertain significance may not explain the seizures or change treatment, so the care team and a genetic counselor interpret it alongside the child's development, seizures, and family history.

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Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Does my child's case of EEM seem to follow a 'multifactorial' pattern or should we look for a single genetic cause?
  2. 2.Given that my child has some learning/developmental challenges, is an epilepsy gene panel or whole-exome sequencing recommended?
  3. 3.If we choose genetic testing, will it include a check for 'copy-number variations' (like microdeletions) as well as individual gene mutations?
  4. 4.How does the 'visual-cortical network' explanation help us understand why light and eye-closure are such strong triggers for my child?
  5. 5.If a 'variant of uncertain significance' is found on a genetic test, how will the care team determine if it's actually related to the seizures?

References

References (17)
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    Dissecting genetics of spectrum of epilepsies with eyelid myoclonia by exome sequencing.

    Coppola A, Krithika S, Iacomino M, et al.

    Epilepsia 2024; (65(3)):779-791 doi:10.1111/epi.17859.

    PMID: 38088023
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    Clinical presentation and evaluation of epilepsy with eyelid myoclonia: Results of an international expert consensus panel.

    Smith KM, Wirrell EC, Andrade DM, et al.

    Epilepsia 2023; (64(9)):2330-2341 doi:10.1111/epi.17683.

    PMID: 37329145
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    Jeavons syndrome featured with visual sensitivity existing as occipital cortex originating focal-to-generalized continuum epilepsy.

    Niu Y, Gong P, Jiao X, Yang Z

    European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 2022; (40()):51-56 doi:10.1016/j.ejpn.2022.07.006.

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    Photosensitive epilepsy is associated with reduced inhibition of alpha rhythm generating networks.

    Vaudano AE, Ruggieri A, Avanzini P, et al.

    Brain : a journal of neurology 2017; (140(4)):981-997 doi:10.1093/brain/awx009.

    PMID: 28334965
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    Contributions of Magnetoencephalography to Understanding Mechanisms of Generalized Epilepsies: Blurring the Boundary Between Focal and Generalized Epilepsies?

    Aung T, Tenney JR, Bagić AI

    Frontiers in neurology 2022; (13()):831546 doi:10.3389/fneur.2022.831546.

    PMID: 35572923
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    Epilepsy with eyelid myoclonia (Jeavons syndrome): Generalized, focal, or combined generalized and focal epilepsy syndrome?

    Gélisse P, Gallegos C, Nilo A, et al.

    Neurophysiologie clinique = Clinical neurophysiology 2024; (54(3)):102947 doi:10.1016/j.neucli.2024.102947.

    PMID: 38422722
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    Epilepsy with eyelid myoclonias (Jeavons syndrome): An electro-clinical study of 40 patients from childhood to adulthood.

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    Seizure 2021; (87()):30-38 doi:10.1016/j.seizure.2021.02.028.

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    Pitfalls in the diagnosis of Jeavons syndrome: a study of 32 cases and review of the literature.

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    Cognitive Function in Genetic Generalized Epilepsies: Insights From Neuropsychology and Neuroimaging.

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    Frontiers in neurology 2020; (11()):144 doi:10.3389/fneur.2020.00144.

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    CHD2-related epilepsy with eyelid myoclonia: Report of three cases.

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    Epileptic disorders : international epilepsy journal with videotape 2025; (27(1)):90-95 doi:10.1002/epd2.20305.

    PMID: 39503459
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    SYNGAP1 encephalopathy: A distinctive generalized developmental and epileptic encephalopathy.

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    Neurology 2019; (92(2)):e96-e107 doi:10.1212/WNL.0000000000006729.

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    NEXMIF encephalopathy: an X-linked disorder with male and female phenotypic patterns.

    Stamberger H, Hammer TB, Gardella E, et al.

    Genetics in medicine : official journal of the American College of Medical Genetics 2021; (23(2)):363-373 doi:10.1038/s41436-020-00988-9.

    PMID: 33144681
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    A 350 kb NEXMIF Microdeletion Identified by Chromosomal Microarray in an Adult Patient with Jeavons Syndrome.

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    PMID: 42074566
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    Molecular and Phenotypic Characterization of the RORB-Related Disorder.

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    Loss of function of the retinoid-related nuclear receptor (RORB) gene and epilepsy.

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    Expanding the clinical and genetic landscape of (developmental) epileptic encephalopathy with spike-and-wave activation in sleep: results from studies of a Turkish cohort.

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    Exome sequencing for patients with developmental and epileptic encephalopathies in clinical practice.

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This page explains the biology, inheritance patterns, and genetic testing considerations for a child with EEM for informational purposes only and does not constitute medical advice. Discuss your child's results and testing options with a pediatric neurologist or genetic counselor.