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

The "Why" Behind the Spasms: Understanding Causes

At a Glance

West Syndrome is a symptom complex triggered by structural brain issues, such as Hypoxic-Ischemic Encephalopathy (HIE) and malformations, or genetic conditions like Tuberous Sclerosis Complex (TSC). Identifying the exact cause is crucial for determining the most effective targeted treatment.

It is helpful to think of West Syndrome not as a single disease, but as a specific reaction the infant brain has to many different “triggers.” Doctors call this a symptom complex. Finding the specific trigger—the underlying etiology—is the most important step in creating a long-term care plan [1][2].

The Brain’s Balancing Act

To understand why spasms happen, it helps to imagine the brain as a complex electrical circuit. For the brain to work correctly, it needs a perfect balance between “go” signals (excitatory) and “stop” signals (inhibitory) [3].

In West Syndrome, this balance is disrupted. Research suggests that certain pathways—specifically the thalamocortical circuits that connect the center of the brain to its outer layer—become overly active or lose their ability to “dampen” electrical noise [4][5]. This causes the chaotic electrical storm seen on an EEG as hypsarrhythmia [6].

Structural Causes

“Structural” means there is a physical difference in how the brain was formed or an injury it sustained.

  • HIE (Hypoxic-Ischemic Encephalopathy): This occurs when a baby’s brain does not get enough oxygen or blood flow around the time of birth [1].
  • Brain Malformations: Some babies are born with small areas of the brain that didn’t develop correctly, such as focal cortical dysplasia (FCD) [2].
  • mTORopathies: This is a group of conditions where a specific growth pathway in the brain (the mTOR pathway) is too active, causing abnormal cell growth and “tangled” brain wiring [7][8].

Genetic Causes

Advances in testing have shown that many cases once called “unknown” actually have a genetic root. Genetic testing doesn’t just target treatment; it also helps parents understand the recurrence risk for future pregnancies.

  • Tuberous Sclerosis Complex (TSC): This is a major cause of West Syndrome. It is a genetic condition that causes non-cancerous tumors to grow in the brain and other organs [9][10].
  • Specific Gene Mutations: Several genes are frequently linked to early-onset spasms:
    • CDKL5: Often involves very early seizures and significant developmental challenges [11][12].
    • ARX: Frequently linked to spasms in boys and can affect how interneurons (the brain’s “stop” signals) move into place during development [13].
    • STXBP1: A mutation that affects how brain cells communicate with each other [14].

Why Finding the Cause Matters

Knowing the cause helps your medical team “target” the treatment. For example, if Tuberous Sclerosis Complex is the cause, doctors often prefer a specific medication called Vigabatrin as the very first treatment [15]. If a structural malformation is found in one specific spot, surgery might eventually be an option to stop the seizures at their source [16][17].

Previous: Recognizing the Spasms | Next: Diagnostic Deep Dive: EEG, MRI, and Genetics

Common questions in this guide

What causes West Syndrome?
West Syndrome is a symptom complex triggered by an underlying issue in the brain. Causes are typically categorized as structural, such as a brain injury or malformation, or genetic, like Tuberous Sclerosis Complex or specific gene mutations.
Why is it important to find the specific cause of my child's infantile spasms?
Identifying the specific cause allows your medical team to target the treatment effectively. For example, if the cause is Tuberous Sclerosis Complex, doctors often prefer a specific medication called vigabatrin as the first treatment.
Can a lack of oxygen at birth cause West Syndrome?
Yes, Hypoxic-Ischemic Encephalopathy (HIE), which occurs when a baby’s brain does not receive enough oxygen or blood flow around the time of birth, is a known structural cause of West Syndrome.
What genetic tests should my child have for infantile spasms?
Doctors often recommend a comprehensive epilepsy gene panel to check for mutations in genes like STXBP1, CDKL5, and ARX. Identifying a genetic cause can help guide treatment decisions and determine recurrence risks for future pregnancies.
Could brain malformations cause my baby's spasms?
Yes, structural differences in how the brain formed, such as focal cortical dysplasia, can trigger West Syndrome. An MRI can help identify these specific malformations, which may sometimes be treated with surgery.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Has our child had a 'comprehensive epilepsy gene panel' to check for mutations like STXBP1 or CDKL5?
  2. 2.Does the MRI show any specific malformations, like focal cortical dysplasia or signs of TSC?
  3. 3.Is there any evidence of HIE (Hypoxic-Ischemic Encephalopathy) from birth that could be the cause?
  4. 4.Could the way my child's spasms look—specifically if they are one-sided—point to a structural cause?
  5. 5.If a specific genetic cause is found, does that change the first-line treatment we should be using?

Questions For You

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References

References (17)
  1. 1

    Genetic Etiology of Infantile Spasms in Peruvian Children: A Multicenter Study.

    Castillo-Huerta NM, Delgado-Mosqueira MG, Diaz-Kuan A, et al.

    Journal of child neurology 2025; 8830738251399269 doi:10.1177/08830738251399269.

    PMID: 41359511
  2. 2

    The genetic landscape and classification of infantile epileptic spasms syndrome requiring surgery due to suspected focal brain malformations.

    Coleman M, Wang M, Snell P, et al.

    Brain communications 2025; (7(1)):fcaf034 doi:10.1093/braincomms/fcaf034.

    PMID: 39926610
  3. 3

    Infantile Spasms in Pediatric Down Syndrome: Potential Mechanisms Driving Therapeutic Considerations.

    Stafstrom CE, Shao LR

    Children (Basel, Switzerland) 2024; (11(12)) doi:10.3390/children11121513.

    PMID: 39767942
  4. 4

    KNOCK, KNOCK, KNOCK-IN ON GABA'S DOOR: GABRB3 Knock-in Mutation Causes Infantile Spasms in Mice.

    Stafstrom CE

    Epilepsy currents 2023; (23(6)):378-380 doi:10.1177/15357597231204594.

    PMID: 38269347
  5. 5

    Spindle density relates to cognitive outcomes in infantile epileptic spasms syndrome with unknown etiology: A retrospective cohort study.

    Daida A, Matsuura R, Hamano SI, et al.

    Epilepsia 2026; (67(5)):2533-2544 doi:10.1002/epi.70130.

    PMID: 41665412
  6. 6

    Hypsarrhythmia in epileptic spasms: Synchrony in chaos.

    Nenadovic V, Whitney R, Boulet J, Cortez MA

    Seizure 2018; (58()):55-61 doi:10.1016/j.seizure.2018.03.026.

    PMID: 29656099
  7. 7

    GATOR1 complex: the common genetic actor in focal epilepsies.

    Baldassari S, Licchetta L, Tinuper P, et al.

    Journal of medical genetics 2016; (53(8)):503-10 doi:10.1136/jmedgenet-2016-103883.

    PMID: 27208208
  8. 8

    Update on Drug Management of Refractory Epilepsy in Tuberous Sclerosis Complex.

    van der Poest Clement E, Jansen FE, Braun KPJ, Peters JM

    Paediatric drugs 2020; (22(1)):73-84 doi:10.1007/s40272-019-00376-0.

    PMID: 31912454
  9. 9

    Central nervous system manifestations of tuberous sclerosis complex.

    Lu DS, Karas PJ, Krueger DA, Weiner HL

    American journal of medical genetics. Part C, Seminars in medical genetics 2018; (178(3)):291-298 doi:10.1002/ajmg.c.31647.

    PMID: 30230171
  10. 10

    Tuberous Sclerosis Complex: A Review.

    Randle SC

    Pediatric annals 2017; (46(4)):e166-e171 doi:10.3928/19382359-20170320-01.

    PMID: 28414398
  11. 11

    Phenotypic manifestations between male and female children with CDKL5 mutations.

    Liang JS, Huang H, Wang JS, Lu JF

    Brain & development 2019; (41(9)):783-789 doi:10.1016/j.braindev.2019.05.003.

    PMID: 31122804
  12. 12

    Clinical manifestation of CDKL5 deficiency disorder and identified mutations in a cohort of Slovak patients.

    Kluckova D, Kolnikova M, Medova V, et al.

    Epilepsy research 2021; (176()):106699 doi:10.1016/j.eplepsyres.2021.106699.

    PMID: 34229227
  13. 13

    A novel C-terminal truncated mutation in hCDKL5 protein causing a severe West syndrome: Comparison with previous truncated mutations and genotype/phenotype correlation.

    Jdila MB, Triki C, Rhouma BB, et al.

    International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience 2019; (72()):22-30 doi:10.1016/j.ijdevneu.2018.09.006.

    PMID: 30236769
  14. 14

    Confirming the contribution and genetic spectrum of de novo mutation in infantile spasms: Evidence from a Chinese cohort.

    Liu L, Liu F, Wang Q, et al.

    Molecular genetics & genomic medicine 2021; (9(6)):e1689 doi:10.1002/mgg3.1689.

    PMID: 33951346
  15. 15

    Comparative Effectiveness of Initial Treatment for Infantile Spasms in a Contemporary US Cohort.

    Grinspan ZM, Knupp KG, Patel AD, et al.

    Neurology 2021; (97(12)):e1217-e1228 doi:10.1212/WNL.0000000000012511.

    PMID: 34266919
  16. 16

    Evaluating the effectiveness of medical therapy in infantile epileptic spasms syndrome due to surgically-remediable lesions.

    Singh A, Hadjinicolaou A, Briscoe-Abath C, et al.

    Epilepsia 2025; (66(5)):1433-1446 doi:10.1111/epi.18291.

    PMID: 39945474
  17. 17

    Epilepsy surgery for children with epileptic spasms: A systematic review and meta-analysis with focus on predictors and outcomes.

    Kolosky T, Goldstein Shipper A, Sun K, et al.

    Epilepsia open 2024; (9(4)):1136-1147 doi:10.1002/epi4.13007.

    PMID: 38953892

This page explains the structural and genetic causes of West Syndrome for educational purposes only. Always consult a pediatric neurologist to determine the specific underlying cause of your child's spasms.

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