Skip to content
How It Works
Explore
Resources Ask a Question
Who It's For
Patients
Decode results, prep for appointments, weigh options.
Caregivers & advocates
Carry the research load for someone you love.
Providers & clinicians
Resources for patients in your practice.
Log In Ask a Question
PubMed This is a summary of 25 peer-reviewed journal articles Updated
Neurology · Developmental and Epileptic Encephalopathy

Beyond the Seizures: Symptoms and Development in DEE

At a Glance

Developmental and Epileptic Encephalopathy (DEE) involves severe seizures alongside significant developmental delays or regression. Non-seizure symptoms like GI issues, sleep disorders, vision problems (CVI), and movement challenges often have the biggest impact on a child's quality of life.

While seizures are often the most visible part of a Developmental and Epileptic Encephalopathy (DEE), they are just one piece of a complex puzzle. For most families, the “non-seizure” symptoms—such as feeding difficulties, sleep issues, and movement challenges—can have an even greater impact on daily quality of life [1][2].

The Seizure Spectrum

Seizures in DEE are often refractory, meaning they are difficult to control with standard medications [3]. Common types include:

  • Infantile Spasms: Brief, repetitive “clustering” movements where the child’s body stiffens or the head drops [4][5].
  • Focal Seizures: These start in one specific part of the brain and may cause twitching on one side of the body or a sudden “blank stare” [4][6].
  • Tonic Seizures: Sudden stiffening of the muscles, often lasting a few seconds to a minute [7].

Delay vs. Regression: Understanding Development

It is important to distinguish between two ways development can be affected in DEE:

  1. Developmental Delay: The child is making progress, but it is much slower than expected for their age [8].
  2. Developmental Regression: The child actually loses skills they once had (e.g., a child who could sit up independently can no longer do so) [9][10].
    In many DEEs, regression is triggered by periods of intense seizure activity or high “electrical noise” in the brain [11].

Life Beyond Seizures: Common Comorbidities

The genetic mutation that causes seizures often affects other systems in the body. These “co-occurring” conditions are called comorbidities.

1. Gastrointestinal (GI) and Feeding Issues

GI problems are incredibly common in DEE. Many children struggle with severe constipation, gastroesophageal reflux (acid reflux), and swallowing difficulties (dysphagia) [12]. These issues can be worsened by certain anti-seizure medications or treatments like the ketogenic diet [12].

2. Sleep Disturbances

Sleep is often severely disrupted in DEE. Children may struggle with insomnia (trouble falling or staying asleep) or sleep apnea (brief pauses in breathing during sleep) [13]. In children with CDKL5 Deficiency Disorder, sleep apnea is a core feature that requires regular monitoring [13].

3. Cortical Visual Impairment (CVI)

Many children with DEE, particularly those with CDKL5 or SCN2A mutations, have CVI [14][15]. This means their eyes are healthy, but the brain’s visual centers cannot process the information correctly [15]. Children with CVI may seem to see “through” objects or only respond to moving, high-contrast items [16].

4. Movement Disorders

Genetic mutations often affect the parts of the brain that control coordination.

  • STXBP1: Frequently presents with a wide range of movement issues, including ataxia (wobbliness), tremors, and dystonia (involuntary muscle contractions) [17][18][19].
  • Hypotonia: Low muscle tone (a “floppy” appearance) is very common across many DEEs and can lead to orthopedic issues like scoliosis over time [14].

5. Autonomic Dysfunction

The autonomic nervous system controls “automatic” functions like heart rate, breathing, and temperature. Some children with DEE may have “storms” where their heart rate spikes, they sweat excessively, or their skin becomes mottled for no obvious reason [20].

Summary of Gene-Specific Challenges

Gene Common Seizure Type Key Non-Seizure Comorbidities
CDKL5 Infantile Spasms [3] Visual impairment (CVI), sleep apnea, GI issues [14][13].
STXBP1 Focal or Spasms [21] Tremors, ataxia, and significant motor delay [17][19].
SCN2A Neonatal Focal [22] Movement disorders, CVI, and autonomic issues [23][20].

Addressing these comorbidities is essential because a child who is well-rested, comfortable (no GI pain), and able to see better will be more engaged in therapy and learning [24][25].

Return to Home Page

Common questions in this guide

What is the difference between developmental delay and regression in DEE?
Developmental delay means a child is making progress, but slower than expected for their age. Developmental regression occurs when a child loses skills they previously mastered, which is often triggered by intense seizure activity in the brain.
What are the most common non-seizure symptoms of DEE?
Common non-seizure symptoms, called comorbidities, include severe reflux and constipation, sleep disturbances like insomnia or sleep apnea, movement issues, and cortical visual impairment (CVI).
Why does my child have vision problems if their eye exams are normal?
Many children with DEE have Cortical Visual Impairment (CVI). This means their eyes are physically healthy, but the brain's visual centers cannot properly process the visual information they receive.
What types of seizures are most common in Developmental and Epileptic Encephalopathy?
Children with DEE often experience refractory seizures, meaning they are very difficult to control with standard medications. Frequent types include infantile spasms, focal seizures, and tonic seizures that cause sudden muscle stiffening.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Which specific seizure types are you seeing on my child's latest EEG (e.g., infantile spasms, focal, or tonic)?
  2. 2.Is my child's lack of progress considered a 'developmental delay' or a 'regression,' and does this change our treatment priority?
  3. 3.Should we schedule a formal assessment for Cortical Visual Impairment (CVI), given my child's specific genetic diagnosis?
  4. 4.Do the tremors or wobbliness I see in my child count as a movement disorder, and are there specific therapies for that?
  5. 5.Is a sleep study necessary to rule out sleep-disordered breathing or apnea?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (25)
  1. 1

    How Encephalopathy Impacts Language Ability: A Scoping Review of the Linguistic Abilities of Adults with Developmental and Epileptic Encephalopathy.

    Papatheodorou I, Stavrakaki S, Koukoulioti V, et al.

    Medicina (Kaunas, Lithuania) 2024; (60(10)) doi:10.3390/medicina60101635.

    PMID: 39459422
  2. 2

    Systematic review of indirect costs to families of children with developmental epileptic encephalopathies.

    Abdelmageed S, Du RY, Carroll M, et al.

    Orphanet journal of rare diseases 2025; (20(1)):579 doi:10.1186/s13023-025-04081-9.

    PMID: 41225515
  3. 3

    CDKL5-associated developmental and epileptic encephalopathy: A long-term, longitudinal electroclinical study of 22 cases.

    Darra F, Monchelato M, Loos M, et al.

    Epilepsy research 2023; (190()):107098 doi:10.1016/j.eplepsyres.2023.107098.

    PMID: 36739728
  4. 4

    Genetic and clinical features of SCN8A developmental and epileptic encephalopathy.

    Kim HJ, Yang D, Kim SH, et al.

    Epilepsy research 2019; (158()):106222 doi:10.1016/j.eplepsyres.2019.106222.

    PMID: 31675620
  5. 5

    Epileptic spasms: a previously unreported manifestation of WDR45 gene mutation.

    Xixis KI, Mikati MA

    Epileptic disorders : international epilepsy journal with videotape 2015; (17(4)):467-72 doi:10.1684/epd.2015.0784.

    PMID: 26609730
  6. 6

    Migrating Focal Seizures and Myoclonic Status in ARV1-Related Encephalopathy.

    Darra F, Lo Barco T, Opri R, et al.

    Neurology. Genetics 2021; (7(3)):e593 doi:10.1212/NXG.0000000000000593.

    PMID: 34017911
  7. 7

    The Expanding Clinical Spectrum of Genetic Pediatric Epileptic Encephalopathies.

    Shbarou R, Mikati MA

    Seminars in pediatric neurology 2016; (23(2)):134-42.

    PMID: 27544470
  8. 8

    Case report: Adult patient with WWOX developmental and epileptic encephalopathy: 40 years of observation.

    Teplyshova A, Sharkov A

    Frontiers in genetics 2024; (15()):1477466 doi:10.3389/fgene.2024.1477466.

    PMID: 39507621
  9. 9

    Expanding the clinical and genetic spectrum of CAD deficiency: an epileptic encephalopathy treatable with uridine supplementation.

    Rymen D, Lindhout M, Spanou M, et al.

    Genetics in medicine : official journal of the American College of Medical Genetics 2020; (22(10)):1589-1597 doi:10.1038/s41436-020-0933-z.

    PMID: 32820246
  10. 10

    A Treatable Genetic Disease Caused by CAD Mutation.

    Peng X, Xia LP, Zhang HJ, et al.

    Frontiers in pediatrics 2022; (10()):771374 doi:10.3389/fped.2022.771374.

    PMID: 35356445
  11. 11

    Developmental and epileptic encephalopathy with spike-wave activation in sleep: From the 'functional ablation' model to a neurodevelopmental network perspective.

    Andreoli L, Bova SM, Veggiotti P

    Developmental medicine and child neurology 2025; (67(10)):1250-1256 doi:10.1111/dmcn.16361.

    PMID: 40356337
  12. 12

    Gastrointestinal Symptoms and Channelopathy-Associated Epilepsy.

    Beck VC, Isom LL, Berg AT

    The Journal of pediatrics 2021; (237()):41-49.e1 doi:10.1016/j.jpeds.2021.06.034.

    PMID: 34181986
  13. 13

    CDKL5 deficiency entails sleep apneas in mice.

    Lo Martire V, Alvente S, Bastianini S, et al.

    Journal of sleep research 2017; (26(4)):495-497 doi:10.1111/jsr.12512.

    PMID: 28230307
  14. 14

    First report of Tunisian patients with CDKL5-related encephalopathy.

    Charfi Triki C, Zouari Mallouli S, Ben Jdila M, et al.

    Epilepsia open 2024; (9(3)):906-917 doi:10.1002/epi4.12824.

    PMID: 37701975
  15. 15

    Cerebral Visual Impairment in CDKL5 Deficiency Disorder Correlates With Developmental Achievement.

    Brock D, Fidell A, Thomas J, et al.

    Journal of child neurology 2021; (36(11)):974-980 doi:10.1177/08830738211019284.

    PMID: 34547934
  16. 16

    CDKL5 deficiency disorder: Relationship between genotype, epilepsy, cortical visual impairment, and development.

    Demarest ST, Olson HE, Moss A, et al.

    Epilepsia 2019; (60(8)):1733-1742 doi:10.1111/epi.16285.

    PMID: 31313283
  17. 17

    Ataxia, tremor, intellectual disability: a case of STXBP1 encephalopathy with a new mutation.

    Değerliyurt A, Kesen GG, Ceylaner S

    The Turkish journal of pediatrics 2019; (61(5)):757-759.

    PMID: 32105008
  18. 18

    Tremor-like subcortical myoclonus in STXBP1 encephalopathy.

    Loussouarn A, Doummar D, Beaugendre Y, et al.

    European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 2021; (34()):62-66 doi:10.1016/j.ejpn.2021.06.005.

    PMID: 34392114
  19. 19

    Developmental and Epileptic Encephalopathies in Adults: An Evolving Field.

    Gorodetsky C, Fasano A

    Neurology 2022; (99(3)):89-91 doi:10.1212/WNL.0000000000200190.

    PMID: 35851555
  20. 20

    Autonomic Characteristics of Sudden Unexpected Death in Epilepsy in Children-A Systematic Review of Studies and Their Relevance to the Management of Epilepsy in Rett Syndrome.

    Singh J, Lanzarini E, Santosh P

    Frontiers in neurology 2020; (11()):632510 doi:10.3389/fneur.2020.632510.

    PMID: 33613425
  21. 21

    Natural History and Developmental Trajectories of Individuals With Disease-Causing Variants in STXBP1.

    Thalwitzer KM, Driedger JH, Xian J, et al.

    Neurology 2023; (101(9)):e879-e891 doi:10.1212/WNL.0000000000207550.

    PMID: 37407264
  22. 22

    Neonatal SCN2A encephalopathy: A peculiar recognizable electroclinical sequence.

    Melikishvili G, Dulac O, Gataullina S

    Epilepsy & behavior : E&B 2020; (111()):107187 doi:10.1016/j.yebeh.2020.107187.

    PMID: 32603808
  23. 23

    Novel homozygous AP3B2 mutations in four individuals with developmental and epileptic encephalopathy: A rare clinical entity.

    Dilber C, Yücel G, Şahin Y

    Clinical neurology and neurosurgery 2022; (223()):107509 doi:10.1016/j.clineuro.2022.107509.

    PMID: 36356440
  24. 24

    Cortical Visual Impairment Across a Range of Neurodevelopmental Disorders: Clinical Characterization, Diagnostic Tool Evaluation, and Association with Developmental Outcomes.

    Abbott M, Angione K, Stringfellow M, et al.

    Journal of child neurology 2026; (41(4)):470-477 doi:10.1177/08830738251361698.

    PMID: 40767165
  25. 25

    Nonseizure symptoms and broader seizure impacts in patients with Dravet syndrome and Lennox-Gastaut syndrome in clinical practice settings: Results from a multinational survey.

    Shah D, Villanueva V, Dlugos D, et al.

    Epilepsia open 2025; (10(6)):1783-1797 doi:10.1002/epi4.70118.

    PMID: 40982357

This page explains DEE symptoms and comorbidities for educational purposes only. Always consult your child's neurologist or care team for specific medical advice, developmental assessments, and treatment plans.

Get notified when new evidence is published on Genetic developmental and epileptic encephalopathy.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.