Infantile Spasms

Complex MONDO:0018097 Pathograph 10 Epilepsy Neurodevelopmental Disorder Neurological Disease

Infantile spasms, now classified as infantile epileptic spasms syndrome (IESS), is an age-dependent developmental and epileptic encephalopathy of infancy. It is characterized by epileptic spasms, usually in clusters, hypsarrhythmia or a related epileptiform EEG pattern, and developmental stagnation or regression. Etiology is heterogeneous, including structural, prenatal, perinatal, postnatal, metabolic, and genetic causes.

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1
Mappings
2
Definitions
3
Inheritance
3
Pathophys.
6
Phenotypes
10
Pathograph
4
Treatments
2
Subtypes
2
Trials
1
Deep Research
🔗

Mappings

MONDO
MONDO:0018097 infantile spasms
skos:exactMatch Orphanet ORPHA:697160
Orphanet ORPHA:697160 is the current infantile epileptic spasms syndrome disease record and MONDO maps infantile spasms to this concept.
📘

Definitions

2
ILAE neonatal and infant epilepsy syndrome definition
ILAE classifies infantile spasms/IESS among epilepsy syndromes with onset in neonates and infants, emphasizing syndrome diagnosis together with etiology.
OTHER
Show evidence (1 reference)
PMID:35503712 SUPPORT Human Clinical
"The International League Against Epilepsy (ILAE) Task Force on Nosology and Definitions proposes a classification and definition of epilepsy syndromes in the neonate and infant with seizure onset up to 2 years of age. "
The ILAE position statement defines epilepsy syndromes with onset in infancy, including infantile epileptic spasms syndrome.
West syndrome electroclinical triad
West syndrome is the historical triad of infantile spasms, hypsarrhythmia on EEG, and developmental regression.
OTHER
Show evidence (1 reference)
PMID:37736852 SUPPORT Human Clinical
"When infantile spasms occur with a concomitant hypsarrhythmia on electroencephalogram (EEG) and developmental regression, it is known as West Syndrome. "
Review article states the clinical-EEG-developmental triad that historically defines West syndrome.
👪

Inheritance

3
Autosomal dominant HP:0000006
A subset of genetic IESS is caused by monoallelic variants in genes recorded by Orphanet, including dominant mechanisms.
Autosomal dominant inheritance
Show evidence (1 reference)
ORPHA:697160 SUPPORT Other
"Autosomal dominant"
Orphanet records autosomal dominant inheritance among the inherited IESS etiologies.
Autosomal recessive HP:0000007
A subset of genetic IESS is caused by biallelic pathogenic variants in autosomal genes.
Autosomal recessive inheritance
Show evidence (1 reference)
ORPHA:697160 SUPPORT Other
"Autosomal recessive"
Orphanet records autosomal recessive inheritance among the inherited IESS etiologies.
X-linked dominant HP:0001423
X-linked genes such as ARX, CDKL5, PIGA, and WDR45 contribute to the inherited IESS spectrum.
X-linked dominant inheritance
Show evidence (1 reference)
ORPHA:697160 SUPPORT Other
"X-linked dominant"
Orphanet records X-linked dominant inheritance for part of the IESS spectrum.
◆

Subtypes

2
IESS with known etiology
IESS with a structural, prenatal, perinatal, postnatal, metabolic, or genetic etiology identified by clinical evaluation.
IESS of unknown etiology
IESS in which standard clinical evaluation does not identify the underlying cause at the time of diagnosis.
⚙

Pathophysiology

3
Heterogeneous developmental brain etiologies
Structural, prenatal, perinatal, postnatal, metabolic, and genetic causes disrupt the developing infant brain and converge on an IESS electroclinical phenotype.
ARX link CDKL5 link GRIN2B link SCN2A link
nervous system development link ⚠ ABNORMAL
brain link
Downstream
Developing brain epileptic network hyperexcitability Diverse etiologies converge on abnormal epileptic network activity in the infant brain.
Developmental and epileptic encephalopathy burden Underlying etiologies contribute to developmental impairment independent of epileptiform activity.
Show evidence (2 references)
PMID:39029407 SUPPORT Human Clinical
"Aetiology was prenatal (40.3 %), perinatal (10.5 %), postnatal (3.7 %), with unknown timing (10.2 %) or with unknown aetiology (33.5 %). "
National cohort demonstrates etiologic heterogeneity across prenatal, perinatal, postnatal, and unknown causes.
ORPHA:697160 SUPPORT Other
"SCN2A | sodium voltage-gated channel alpha subunit 2 | hgnc:10588 | Disease-causing germline mutation(s) in"
Orphanet records SCN2A and other genes as disease-causing in genetic IESS.
Developing brain epileptic network hyperexcitability
The IESS phenotype reflects abnormal synchronized activity in immature cortical-subcortical networks, producing epileptic spasms and the hypsarrhythmic EEG pattern.
neuron link
trans-synaptic signaling link ⚠ ABNORMAL
brain link
Downstream
Infantile spasms Epileptic network discharges produce clusters of infantile spasms.
Hypsarrhythmia The same epileptic encephalopathy produces the hypsarrhythmic EEG pattern.
Developmental and epileptic encephalopathy burden Epileptic encephalopathy contributes to developmental impairment alongside the underlying etiology.
Show evidence (2 references)
PMID:37736852 SUPPORT Human Clinical
"Infantile spasms, newly classified as infantile epileptic spasm syndrome (IESS), occur in children under 2 years of age and present as an occur as brief, symmetrical, contractions of the musculature of the neck, trunk, and extremities. "
Review describes the age-dependent epileptic spasm phenotype produced by the abnormal infantile network state.
PMID:27838190 SUPPORT Human Clinical
"enrolled infants who had a clinical diagnosis of infantile spasms and a hypsarrhythmic (or similar) EEG no more than 7 days before enrolment. "
Trial inclusion criteria show that infantile spasms and hypsarrhythmic or similar EEG activity form the electroclinical syndrome.
Developmental and epileptic encephalopathy burden
IESS is part of the developmental and epileptic encephalopathy spectrum: developmental impairment reflects both the underlying etiology and the epileptic encephalopathy.
nervous system development link ⚠ ABNORMAL
Downstream
Developmental regression Epileptic encephalopathy is associated with loss of developmental skills.
Global developmental delay The combined etiologic and epileptic burden contributes to global developmental delay.
Show evidence (2 references)
PMID:35503712 SUPPORT Human Clinical
"developmental and epileptic encephalopathies, diseases where there is developmental impairment related to both the underlying etiology independent of epileptiform activity and the epileptic encephalopathy. "
ILAE statement defines developmental and epileptic encephalopathies as disorders where etiology and epileptiform activity both contribute to developmental impairment.
PMID:39029407 SUPPORT Human Clinical
"At latest follow-up severe neurodevelopmental outcome was seen in 44.2 % and 76.4 % still had epilepsy."
Danish cohort quantifies long-term neurodevelopmental and epilepsy burden after IESS.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Infantile Spasms Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

6
Integument 1
Cutaneous signs of underlying etiology FREQUENT Abnormal skin morphology (HP:0011121)
Show evidence (1 reference)
ORPHA:697160 SUPPORT Other
"HP:0011121 | Abnormal skin morphology | Frequent (79-30%)"
Orphanet records abnormal skin morphology as frequent for the IESS spectrum.
Nervous System 4
Hypsarrhythmia VERY_FREQUENT Hypsarrhythmia (HP:0002521)
Show evidence (2 references)
ORPHA:697160 SUPPORT Other
"HP:0002521 | Hypsarrhythmia | Very frequent (99-80%)"
Orphanet records hypsarrhythmia as very frequent in IESS.
PMID:27838190 SUPPORT Human Clinical
"clinical diagnosis of infantile spasms and a hypsarrhythmic (or similar) EEG"
ICISS trial used hypsarrhythmic or similar EEG as part of the electroclinical inclusion criteria.
Developmental regression VERY_FREQUENT Developmental regression (HP:0002376)
Show evidence (2 references)
ORPHA:697160 SUPPORT Other
"HP:0002376 | Developmental regression | Very frequent (99-80%)"
Orphanet records developmental regression as very frequent in IESS.
PMID:37736852 SUPPORT Human Clinical
"concomitant hypsarrhythmia on electroencephalogram (EEG) and developmental regression"
Review includes developmental regression in the West syndrome triad.
Myoclonus VERY_FREQUENT Myoclonus (HP:0001336)
Show evidence (1 reference)
ORPHA:697160 SUPPORT Other
"HP:0001336 | Myoclonus | Very frequent (99-80%)"
Orphanet records myoclonus as very frequent in IESS.
Global developmental delay Global developmental delay (HP:0001263)
Show evidence (2 references)
PMID:35503712 SUPPORT Human Clinical
"developmental impairment related to both the underlying etiology independent of epileptiform activity and the epileptic encephalopathy"
ILAE statement supports developmental impairment as intrinsic to developmental and epileptic encephalopathy syndromes.
PMID:39029407 SUPPORT Human Clinical
"severe neurodevelopmental outcome was seen in 44.2 %"
National cohort documents severe neurodevelopmental outcome in a large fraction of children with IESS.
Other 1
Infantile spasms VERY_FREQUENT Infantile spasms (HP:0012469)
Show evidence (1 reference)
ORPHA:697160 SUPPORT Other
"HP:0012469 | Infantile spasms | Very frequent (99-80%)"
Orphanet records infantile spasms as very frequent in IESS.
💊

Treatments

4
Hormonal therapy with ACTH or high-dose prednisolone
Action: Pharmacotherapy NCIT:C15986
Agent: corticotropin ↗ prednisolone ↗
ACTH, tetracosactide, or high-dose prednisolone are first-line hormonal therapies for IESS, aiming for rapid cessation of spasms and EEG improvement.
Mechanism Target:
MODULATES Developing brain epileptic network hyperexcitability — Hormonal therapy reduces the epileptic network activity that produces spasms and hypsarrhythmia.
Target Phenotypes: Infantile spasms ↗ Hypsarrhythmia ↗
Show evidence (2 references)
PMID:35765990 SUPPORT Human Clinical
"Treatments including ACTH and high dose prednisolone are more effective in achieving electroclinical and clinical remissions for infantile spasms."
Network meta-analysis supports ACTH and high-dose prednisolone as effective first-line therapies.
PMID:31903560 SUPPORT Human Clinical
"Prednisolone/prednisone elicits a similar electroclinical response as ACTH for infantile spasms"
RCT meta-analysis supports prednisolone/prednisone as an ACTH alternative for electroclinical response.
Vigabatrin
Action: anticonvulsant agent therapy MAXO:0000167
Agent: vigabatrin ↗
Vigabatrin is an antiseizure medication used for IESS, especially when tuberous sclerosis complex is the underlying cause; it increases brain GABA concentrations but requires visual-field toxicity risk management.
Mechanism Target:
MODULATES Developing brain epileptic network hyperexcitability — Vigabatrin increases inhibitory GABA tone and reduces epileptic spasm frequency.
Target Phenotypes: Infantile spasms ↗
Show evidence (3 references)
PMID:22364326 SUPPORT Human Clinical
"Clinical studies have shown that vigabatrin is superior to placebo in decreasing the frequency of infantile spasms."
Review summarizes clinical trial evidence for vigabatrin reducing infantile spasms.
PMID:22364326 SUPPORT Human Clinical
"In tuberous sclerosis, vigabatrin may be considered the first-line treatment for IS."
Supports the specific first-line role of vigabatrin in TSC-associated IESS.
PMID:22364326 SUPPORT Human Clinical
"The mode of action is increasing concentrations of the inhibitory neurotransmitter GABA in the brain."
Provides the mechanism rationale for vigabatrin modulation of epileptic network activity.
Combination hormonal therapy plus vigabatrin
Action: Pharmacotherapy NCIT:C15986
Agent: corticotropin ↗ prednisolone ↗ vigabatrin ↗
Combined hormonal therapy with vigabatrin can be used as initial therapy to increase early spasm cessation compared with hormonal therapy alone.
Target Phenotypes: Infantile spasms ↗
Show evidence (2 references)
PMID:27838190 SUPPORT Human Clinical
"Between days 14 and 42 inclusive no spasms were witnessed in 133 (72%) of 186 patients on hormonal therapy with vigabatrin compared with 108 (57%) of 191 patients on hormonal therapy alone "
ICISS randomized trial shows higher early spasm cessation with combination hormonal therapy plus vigabatrin.
PMID:27838190 SUPPORT Human Clinical
"Hormonal therapy with vigabatrin is significantly more effective at stopping infantile spasms than hormonal therapy alone."
ICISS interpretation directly supports combination therapy efficacy.
Genetic counseling
Action: genetic counseling MAXO:0000079
Genetic counseling is indicated when IESS has an inherited or de novo genetic etiology, because the spectrum includes autosomal dominant, autosomal recessive, and X-linked genetic causes.
Show evidence (1 reference)
ORPHA:697160 SUPPORT Other
"Autosomal dominant"
Orphanet's genetic inheritance assertions support counseling for recurrence-risk assessment.
🔬

Clinical Trials

2
NCT04302116 NOT_APPLICABLE RECRUITING
Randomized trial comparing vigabatrin plus high-dose prednisolone combination therapy with vigabatrin alone for infantile spasms.
Target Phenotypes: Infantile spasms ↗ Hypsarrhythmia ↗
Show evidence (1 reference)
clinicaltrials:NCT04302116 SUPPORT Human Clinical
"this study is aimed to compare the efficacy of vigabatrin with high dose prednisolone combination therapy and vigabatrin alone."
ClinicalTrials.gov record describes the active randomized comparison of combination therapy versus vigabatrin alone.
NCT04289467 PHASE_II RECRUITING
Phase II trial of fenfluramine for refractory infantile spasms that have not responded to vigabatrin and ACTH.
Target Phenotypes: Refractory infantile spasms ↗
Show evidence (1 reference)
clinicaltrials:NCT04289467 SUPPORT Human Clinical
"children with refractory infantile spasms (also called epileptic spasms or West syndrome) will be treated with fenfluramine"
ClinicalTrials.gov record describes fenfluramine evaluation for refractory infantile spasms.
{ }

Source YAML

click to show 
name: Infantile Spasms
creation_date: "2026-05-07T12:19:58Z"
updated_date: "2026-05-07T12:49:32Z"
description: >
  Infantile spasms, now classified as infantile epileptic spasms syndrome
  (IESS), is an age-dependent developmental and epileptic encephalopathy of
  infancy. It is characterized by epileptic spasms, usually in clusters,
  hypsarrhythmia or a related epileptiform EEG pattern, and developmental
  stagnation or regression. Etiology is heterogeneous, including structural,
  prenatal, perinatal, postnatal, metabolic, and genetic causes.
category: Complex
parents:
- Epilepsy
- Neurodevelopmental Disorder
- Neurological Disease
synonyms:
- West syndrome
- West's syndrome
- Infantile epileptic spasms syndrome
- IESS
disease_term:
  preferred_term: infantile spasms
  term:
    id: MONDO:0018097
    label: infantile spasms
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0018097
      label: infantile spasms
    mapping_predicate: skos:exactMatch
    mapping_source: Orphanet ORPHA:697160
    mapping_justification: >
      Orphanet ORPHA:697160 is the current infantile epileptic spasms syndrome
      disease record and MONDO maps infantile spasms to this concept.
external_assertions:
- name: Orphanet infantile epileptic spasms syndrome record
  source: Orphanet
  assertion_type: structured_disease_record
  external_id: ORPHA:697160
  url: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=697160
  description: >
    Orphanet's ORPHA:697160 structured record for infantile epileptic spasms
    syndrome includes the inheritance modes, disease-gene assertions, HPO
    phenotype rows, and external cross-references used in this entry.
  evidence:
  - reference: ORPHA:697160
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0012469 | Infantile spasms | Very frequent (99-80%)"
    explanation: Orphanet lists infantile spasms as a very frequent phenotype for ORPHA:697160.
  - reference: ORPHA:697160
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "ARX | aristaless related homeobox | hgnc:18060 | Disease-causing germline mutation(s) in"
    explanation: Orphanet records ARX among disease-causing genes for the IESS spectrum.
- name: Orphanet West syndrome legacy record
  source: Orphanet
  assertion_type: structured_disease_record
  external_id: ORPHA:3451
  url: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=3451
  description: >
    Orphanet's ORPHA:3451 West syndrome record is retained as a legacy exact
    cross-reference to MONDO:0018097 and the ICD-11 IESS/West syndrome concept.
  evidence:
  - reference: ORPHA:3451
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "MONDO:0018097 | Exact"
    explanation: ORPHA:3451 maps exactly to the MONDO infantile spasms concept used by this entry.
definitions:
- name: ILAE neonatal and infant epilepsy syndrome definition
  definition_type: OTHER
  description: >
    ILAE classifies infantile spasms/IESS among epilepsy syndromes with onset in
    neonates and infants, emphasizing syndrome diagnosis together with etiology.
  evidence:
  - reference: PMID:35503712
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      The International League Against Epilepsy (ILAE) Task Force on Nosology and Definitions proposes a classification and definition of epilepsy syndromes in the neonate and infant with seizure onset up to 2 years of age.
    explanation: The ILAE position statement defines epilepsy syndromes with onset in infancy, including infantile epileptic spasms syndrome.
- name: West syndrome electroclinical triad
  definition_type: OTHER
  description: >
    West syndrome is the historical triad of infantile spasms, hypsarrhythmia on
    EEG, and developmental regression.
  evidence:
  - reference: PMID:37736852
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      When infantile spasms occur with a concomitant hypsarrhythmia on electroencephalogram (EEG) and developmental regression, it is known as West Syndrome.
    explanation: Review article states the clinical-EEG-developmental triad that historically defines West syndrome.
prevalence:
- population: Denmark, births 1996-2019
  percentage: 22 per 100,000 live births
  evidence:
  - reference: PMID:39029407
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: The incidence of IESS was 22 per 100.000 live births.
    explanation: National retrospective Danish cohort provides a population incidence estimate for IESS.
has_subtypes:
- name: Known etiology
  display_name: IESS with known etiology
  description: >
    IESS with a structural, prenatal, perinatal, postnatal, metabolic, or
    genetic etiology identified by clinical evaluation.
- name: Unknown etiology
  display_name: IESS of unknown etiology
  description: >
    IESS in which standard clinical evaluation does not identify the underlying
    cause at the time of diagnosis.
inheritance:
- name: Autosomal dominant
  inheritance_term:
    preferred_term: Autosomal dominant inheritance
    term:
      id: HP:0000006
      label: Autosomal dominant inheritance
  description: >
    A subset of genetic IESS is caused by monoallelic variants in genes recorded
    by Orphanet, including dominant mechanisms.
  evidence:
  - reference: ORPHA:697160
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Autosomal dominant"
    explanation: Orphanet records autosomal dominant inheritance among the inherited IESS etiologies.
- name: Autosomal recessive
  inheritance_term:
    preferred_term: Autosomal recessive inheritance
    term:
      id: HP:0000007
      label: Autosomal recessive inheritance
  description: >
    A subset of genetic IESS is caused by biallelic pathogenic variants in
    autosomal genes.
  evidence:
  - reference: ORPHA:697160
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Autosomal recessive"
    explanation: Orphanet records autosomal recessive inheritance among the inherited IESS etiologies.
- name: X-linked dominant
  inheritance_term:
    preferred_term: X-linked dominant inheritance
    term:
      id: HP:0001423
      label: X-linked dominant inheritance
  description: >
    X-linked genes such as ARX, CDKL5, PIGA, and WDR45 contribute to the
    inherited IESS spectrum.
  evidence:
  - reference: ORPHA:697160
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "X-linked dominant"
    explanation: Orphanet records X-linked dominant inheritance for part of the IESS spectrum.
pathophysiology:
- name: Heterogeneous developmental brain etiologies
  description: >
    Structural, prenatal, perinatal, postnatal, metabolic, and genetic causes
    disrupt the developing infant brain and converge on an IESS electroclinical
    phenotype.
  genes:
  - preferred_term: ARX
    term:
      id: hgnc:18060
      label: ARX
  - preferred_term: CDKL5
    term:
      id: hgnc:11411
      label: CDKL5
  - preferred_term: GRIN2B
    term:
      id: hgnc:4586
      label: GRIN2B
  - preferred_term: SCN2A
    term:
      id: hgnc:10588
      label: SCN2A
  biological_processes:
  - preferred_term: nervous system development
    term:
      id: GO:0007399
      label: nervous system development
    modifier: ABNORMAL
  locations:
  - preferred_term: brain
    term:
      id: UBERON:0000955
      label: brain
  evidence:
  - reference: PMID:39029407
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      Aetiology was prenatal (40.3 %), perinatal (10.5 %), postnatal (3.7 %), with unknown timing (10.2 %) or with unknown aetiology (33.5 %).
    explanation: National cohort demonstrates etiologic heterogeneity across prenatal, perinatal, postnatal, and unknown causes.
  - reference: ORPHA:697160
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "SCN2A | sodium voltage-gated channel alpha subunit 2 | hgnc:10588 | Disease-causing germline mutation(s) in"
    explanation: Orphanet records SCN2A and other genes as disease-causing in genetic IESS.
  downstream:
  - target: Developing brain epileptic network hyperexcitability
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: Diverse etiologies converge on abnormal epileptic network activity in the infant brain.
  - target: Developmental and epileptic encephalopathy burden
    causal_link_type: DIRECT
    description: Underlying etiologies contribute to developmental impairment independent of epileptiform activity.
- name: Developing brain epileptic network hyperexcitability
  description: >
    The IESS phenotype reflects abnormal synchronized activity in immature
    cortical-subcortical networks, producing epileptic spasms and the
    hypsarrhythmic EEG pattern.
  cell_types:
  - preferred_term: neuron
    term:
      id: CL:0000540
      label: neuron
  biological_processes:
  - preferred_term: trans-synaptic signaling
    term:
      id: GO:0099537
      label: trans-synaptic signaling
    modifier: ABNORMAL
  locations:
  - preferred_term: brain
    term:
      id: UBERON:0000955
      label: brain
  evidence:
  - reference: PMID:37736852
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      Infantile spasms, newly classified as infantile epileptic spasm syndrome (IESS), occur in children under 2 years of age and present as an occur as brief, symmetrical, contractions of the musculature of the neck, trunk, and extremities.
    explanation: Review describes the age-dependent epileptic spasm phenotype produced by the abnormal infantile network state.
  - reference: PMID:27838190
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      enrolled infants who had a clinical diagnosis of infantile spasms and a hypsarrhythmic (or similar) EEG no more than 7 days before enrolment.
    explanation: Trial inclusion criteria show that infantile spasms and hypsarrhythmic or similar EEG activity form the electroclinical syndrome.
  downstream:
  - target: Infantile spasms
    causal_link_type: DIRECT
    description: Epileptic network discharges produce clusters of infantile spasms.
  - target: Hypsarrhythmia
    causal_link_type: DIRECT
    description: The same epileptic encephalopathy produces the hypsarrhythmic EEG pattern.
  - target: Developmental and epileptic encephalopathy burden
    causal_link_type: DIRECT
    description: Epileptic encephalopathy contributes to developmental impairment alongside the underlying etiology.
- name: Developmental and epileptic encephalopathy burden
  description: >
    IESS is part of the developmental and epileptic encephalopathy spectrum:
    developmental impairment reflects both the underlying etiology and the
    epileptic encephalopathy.
  biological_processes:
  - preferred_term: nervous system development
    term:
      id: GO:0007399
      label: nervous system development
    modifier: ABNORMAL
  evidence:
  - reference: PMID:35503712
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      developmental and epileptic encephalopathies, diseases where there is developmental impairment related to both the underlying etiology independent of epileptiform activity and the epileptic encephalopathy.
    explanation: ILAE statement defines developmental and epileptic encephalopathies as disorders where etiology and epileptiform activity both contribute to developmental impairment.
  - reference: PMID:39029407
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: At latest follow-up severe neurodevelopmental outcome was seen in 44.2 % and 76.4 % still had epilepsy.
    explanation: Danish cohort quantifies long-term neurodevelopmental and epilepsy burden after IESS.
  downstream:
  - target: Developmental regression
    causal_link_type: DIRECT
    description: Epileptic encephalopathy is associated with loss of developmental skills.
  - target: Global developmental delay
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Developmental impairment is related to both underlying etiology and epileptic encephalopathy.
    description: The combined etiologic and epileptic burden contributes to global developmental delay.
phenotypes:
- name: Infantile spasms
  category: Clinical
  frequency: VERY_FREQUENT
  diagnostic: true
  description: >
    Epileptic spasms beginning in infancy, often occurring in clusters, are the
    cardinal clinical seizure type of IESS.
  phenotype_term:
    preferred_term: Infantile spasms
    term:
      id: HP:0012469
      label: Infantile spasms
  evidence:
  - reference: ORPHA:697160
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0012469 | Infantile spasms | Very frequent (99-80%)"
    explanation: Orphanet records infantile spasms as very frequent in IESS.
- name: Hypsarrhythmia
  category: Diagnostic
  frequency: VERY_FREQUENT
  diagnostic: true
  description: >
    Hypsarrhythmia or a modified/similar epileptiform EEG pattern is the
    characteristic interictal EEG abnormality supporting IESS diagnosis.
  phenotype_term:
    preferred_term: Hypsarrhythmia
    term:
      id: HP:0002521
      label: Hypsarrhythmia
  evidence:
  - reference: ORPHA:697160
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002521 | Hypsarrhythmia | Very frequent (99-80%)"
    explanation: Orphanet records hypsarrhythmia as very frequent in IESS.
  - reference: PMID:27838190
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "clinical diagnosis of infantile spasms and a hypsarrhythmic (or similar) EEG"
    explanation: ICISS trial used hypsarrhythmic or similar EEG as part of the electroclinical inclusion criteria.
- name: Developmental regression
  category: Clinical
  frequency: VERY_FREQUENT
  diagnostic: true
  description: >
    Loss or stagnation of developmental skills is a core West syndrome feature
    and a major contributor to long-term disability.
  phenotype_term:
    preferred_term: Developmental regression
    term:
      id: HP:0002376
      label: Developmental regression
  evidence:
  - reference: ORPHA:697160
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002376 | Developmental regression | Very frequent (99-80%)"
    explanation: Orphanet records developmental regression as very frequent in IESS.
  - reference: PMID:37736852
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "concomitant hypsarrhythmia on electroencephalogram (EEG) and developmental regression"
    explanation: Review includes developmental regression in the West syndrome triad.
- name: Myoclonus
  category: Clinical
  frequency: VERY_FREQUENT
  description: >
    Myoclonic or spasm-like motor events are part of the IESS seizure
    presentation and overlap clinically with epileptic spasms.
  phenotype_term:
    preferred_term: Myoclonus
    term:
      id: HP:0001336
      label: Myoclonus
  evidence:
  - reference: ORPHA:697160
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001336 | Myoclonus | Very frequent (99-80%)"
    explanation: Orphanet records myoclonus as very frequent in IESS.
- name: Global developmental delay
  category: Clinical
  description: >
    Developmental impairment commonly persists beyond the acute spasm period,
    especially when etiology is structural or symptomatic and treatment is
    delayed.
  phenotype_term:
    preferred_term: Global developmental delay
    term:
      id: HP:0001263
      label: Global developmental delay
  evidence:
  - reference: PMID:35503712
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "developmental impairment related to both the underlying etiology independent of epileptiform activity and the epileptic encephalopathy"
    explanation: ILAE statement supports developmental impairment as intrinsic to developmental and epileptic encephalopathy syndromes.
  - reference: PMID:39029407
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "severe neurodevelopmental outcome was seen in 44.2 %"
    explanation: National cohort documents severe neurodevelopmental outcome in a large fraction of children with IESS.
- name: Cutaneous signs of underlying etiology
  category: Clinical
  frequency: FREQUENT
  description: >
    Skin abnormalities may be present when IESS is caused by a neurocutaneous or
    syndromic genetic etiology; they should be interpreted as etiologic clues
    rather than as defining spasm semiology.
  phenotype_term:
    preferred_term: Abnormal skin morphology
    term:
      id: HP:0011121
      label: Abnormal skin morphology
  evidence:
  - reference: ORPHA:697160
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0011121 | Abnormal skin morphology | Frequent (79-30%)"
    explanation: Orphanet records abnormal skin morphology as frequent for the IESS spectrum.
diagnosis:
- name: Video EEG and electroclinical syndrome diagnosis
  description: >
    Diagnosis is based on recognizing the spasm semiology together with EEG
    evidence of hypsarrhythmia or a similar epileptiform pattern; video-EEG is
    used to confirm events and assess electroclinical response.
  diagnosis_term:
    preferred_term: electroencephalography
    term:
      id: MAXO:0000932
      label: electroencephalography
  evidence:
  - reference: PMID:27838190
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      enrolled infants who had a clinical diagnosis of infantile spasms and a hypsarrhythmic (or similar) EEG no more than 7 days before enrolment.
    explanation: Trial criteria demonstrate the diagnostic pairing of clinical spasms with a hypsarrhythmic or similar EEG pattern.
- name: Etiologic evaluation with neuroimaging and genetic testing
  description: >
    After electroclinical diagnosis, evaluation should seek an underlying
    structural, metabolic, or genetic cause using neuroimaging, metabolic
    assessment, and genetic testing as clinically appropriate.
  diagnosis_term:
    preferred_term: genetic testing
    term:
      id: MAXO:0000127
      label: genetic testing
  evidence:
  - reference: PMID:35503712
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "For each syndrome, we report epidemiology, clinical course, seizure types, electroencephalography (EEG), neuroimaging, genetics, and differential diagnosis."
    explanation: ILAE syndrome framework includes EEG, neuroimaging, genetics, and differential diagnosis for infant epilepsy syndromes.
  - reference: PMID:35503712
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Guidance is given on the criteria for syndrome diagnosis in resource-limited regions where laboratory confirmation, including EEG, MRI, and genetic testing, might not be available."
    explanation: ILAE notes EEG, MRI, and genetic testing as usual confirmatory resources for syndrome diagnosis and etiologic evaluation.
treatments:
- name: Hormonal therapy with ACTH or high-dose prednisolone
  description: >
    ACTH, tetracosactide, or high-dose prednisolone are first-line hormonal
    therapies for IESS, aiming for rapid cessation of spasms and EEG
    improvement.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: corticotropin
      term:
        id: CHEBI:3892
        label: corticotropin
    - preferred_term: prednisolone
      term:
        id: CHEBI:8378
        label: prednisolone
  target_phenotypes:
  - preferred_term: Infantile spasms
    term:
      id: HP:0012469
      label: Infantile spasms
  - preferred_term: Hypsarrhythmia
    term:
      id: HP:0002521
      label: Hypsarrhythmia
  target_mechanisms:
  - target: Developing brain epileptic network hyperexcitability
    treatment_effect: MODULATES
    description: Hormonal therapy reduces the epileptic network activity that produces spasms and hypsarrhythmia.
  evidence:
  - reference: PMID:35765990
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Treatments including ACTH and high dose prednisolone are more effective in achieving electroclinical and clinical remissions for infantile spasms."
    explanation: Network meta-analysis supports ACTH and high-dose prednisolone as effective first-line therapies.
  - reference: PMID:31903560
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Prednisolone/prednisone elicits a similar electroclinical response as ACTH for infantile spasms"
    explanation: RCT meta-analysis supports prednisolone/prednisone as an ACTH alternative for electroclinical response.
- name: Vigabatrin
  description: >
    Vigabatrin is an antiseizure medication used for IESS, especially when
    tuberous sclerosis complex is the underlying cause; it increases brain GABA
    concentrations but requires visual-field toxicity risk management.
  treatment_term:
    preferred_term: anticonvulsant agent therapy
    term:
      id: MAXO:0000167
      label: anticonvulsant agent therapy
    therapeutic_agent:
    - preferred_term: vigabatrin
      term:
        id: CHEBI:63638
        label: vigabatrin
  target_phenotypes:
  - preferred_term: Infantile spasms
    term:
      id: HP:0012469
      label: Infantile spasms
  target_mechanisms:
  - target: Developing brain epileptic network hyperexcitability
    treatment_effect: MODULATES
    description: Vigabatrin increases inhibitory GABA tone and reduces epileptic spasm frequency.
  evidence:
  - reference: PMID:22364326
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Clinical studies have shown that vigabatrin is superior to placebo in decreasing the frequency of infantile spasms."
    explanation: Review summarizes clinical trial evidence for vigabatrin reducing infantile spasms.
  - reference: PMID:22364326
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In tuberous sclerosis, vigabatrin may be considered the first-line treatment for IS."
    explanation: Supports the specific first-line role of vigabatrin in TSC-associated IESS.
  - reference: PMID:22364326
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The mode of action is increasing concentrations of the inhibitory neurotransmitter GABA in the brain."
    explanation: Provides the mechanism rationale for vigabatrin modulation of epileptic network activity.
- name: Combination hormonal therapy plus vigabatrin
  description: >
    Combined hormonal therapy with vigabatrin can be used as initial therapy to
    increase early spasm cessation compared with hormonal therapy alone.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: corticotropin
      term:
        id: CHEBI:3892
        label: corticotropin
    - preferred_term: prednisolone
      term:
        id: CHEBI:8378
        label: prednisolone
    - preferred_term: vigabatrin
      term:
        id: CHEBI:63638
        label: vigabatrin
  target_phenotypes:
  - preferred_term: Infantile spasms
    term:
      id: HP:0012469
      label: Infantile spasms
  evidence:
  - reference: PMID:27838190
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      Between days 14 and 42 inclusive no spasms were witnessed in 133 (72%) of 186 patients on hormonal therapy with vigabatrin compared with 108 (57%) of 191 patients on hormonal therapy alone
    explanation: ICISS randomized trial shows higher early spasm cessation with combination hormonal therapy plus vigabatrin.
  - reference: PMID:27838190
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Hormonal therapy with vigabatrin is significantly more effective at stopping infantile spasms than hormonal therapy alone."
    explanation: ICISS interpretation directly supports combination therapy efficacy.
- name: Genetic counseling
  description: >
    Genetic counseling is indicated when IESS has an inherited or de novo
    genetic etiology, because the spectrum includes autosomal dominant,
    autosomal recessive, and X-linked genetic causes.
  treatment_term:
    preferred_term: genetic counseling
    term:
      id: MAXO:0000079
      label: genetic counseling
  evidence:
  - reference: ORPHA:697160
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Autosomal dominant"
    explanation: Orphanet's genetic inheritance assertions support counseling for recurrence-risk assessment.
clinical_trials:
- name: NCT04302116
  phase: NOT_APPLICABLE
  status: RECRUITING
  description: >
    Randomized trial comparing vigabatrin plus high-dose prednisolone
    combination therapy with vigabatrin alone for infantile spasms.
  target_phenotypes:
  - preferred_term: Infantile spasms
    term:
      id: HP:0012469
      label: Infantile spasms
  - preferred_term: Hypsarrhythmia
    term:
      id: HP:0002521
      label: Hypsarrhythmia
  evidence:
  - reference: clinicaltrials:NCT04302116
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "this study is aimed to compare the efficacy of vigabatrin with high dose prednisolone combination therapy and vigabatrin alone."
    explanation: ClinicalTrials.gov record describes the active randomized comparison of combination therapy versus vigabatrin alone.
- name: NCT04289467
  phase: PHASE_II
  status: RECRUITING
  description: >
    Phase II trial of fenfluramine for refractory infantile spasms that have
    not responded to vigabatrin and ACTH.
  target_phenotypes:
  - preferred_term: Refractory infantile spasms
    term:
      id: HP:0012469
      label: Infantile spasms
  evidence:
  - reference: clinicaltrials:NCT04289467
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "children with refractory infantile spasms (also called epileptic spasms or West syndrome) will be treated with fenfluramine"
    explanation: ClinicalTrials.gov record describes fenfluramine evaluation for refractory infantile spasms.
notes: >
  Orphanet also lists the generic root term HP:0000707 Abnormality of the
  nervous system for ORPHA:697160. This entry does not model that root term as
  a separate phenotype because the more specific IESS neurologic phenotypes are
  represented directly.
references: []
📚

References & Deep Research

Deep Research

1
Infantile Spasms Deep Research Fallback ▸

Infantile Spasms Deep Research Fallback

Provider attempts

  • timeout 75s just research-disorder falcon Infantile_Spasms
  • Result: timed out with Recipe research-disorder was terminated by signal 15.
  • timeout 75s just research-disorder openai Infantile_Spasms
  • Result: timed out with Recipe research-disorder was terminated by signal 15.

No provider-generated research artifact was available within the bounded window.

Evidence-backed curation scope

The entry was curated from deterministic generated caches and primary/secondary biomedical sources:

  • Orphadata structured records:
  • ORPHA:697160 Infantile epileptic spasms syndrome, including inheritance, genes, phenotypes, and cross-references.
  • ORPHA:3451 West syndrome legacy exact mapping to MONDO:0018097.
  • PubMed caches:
  • PMID:35503712 ILAE classification and definition of epilepsy syndromes with onset in neonates and infants.
  • PMID:39029407 Danish national IESS epidemiology and outcome cohort.
  • PMID:27838190 ICISS randomized trial of hormonal therapy with or without vigabatrin.
  • PMID:16239177 UKISS randomized trial follow-up comparing hormone treatment and vigabatrin.
  • PMID:31903560 prednisolone/prednisone versus ACTH RCT meta-analysis.
  • PMID:35765990 network meta-analysis of first-line IESS treatments.
  • PMID:22364326 vigabatrin monotherapy review, including mechanism and TSC-specific first-line use.
  • PMID:37736852 current treatment-modality review and West syndrome triad wording.
  • ClinicalTrials.gov caches:
  • clinicaltrials:NCT04302116 vigabatrin plus high-dose prednisolone versus vigabatrin alone.
  • clinicaltrials:NCT04289467 fenfluramine for refractory infantile spasms.

Modeling notes

  • ORPHA:697160 lists the generic HPO root HP:0000707 Abnormality of the nervous system. It is intentionally documented in YAML notes rather than modeled as a phenotype because the entry includes more specific neurologic findings.
  • Treatment modeling emphasizes first-line hormonal therapy, vigabatrin, and combination therapy because these have cached RCT/meta-analysis support.
  • Refractory fenfluramine is represented as an active Phase II clinical trial rather than a standard treatment.