Lennox-Gastaut Syndrome (LGS) Foundation

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Lennox-Gastaut Syndrome (LGS) is a severe epilepsy syndrome that develops in young children and often leads to lifelong disability. Most people with LGS have seizures that begin in the first three years of life and will have developmental delay within five years of seizure onset.

Last updated 04/30/2026

Clinical

Disease Class

Developmental anomalies during embryogenesis

Diseases due to toxic effects

Epilepsy and seizure disorders

Genetic diseases

Immunological diseases

Inherited metabolic disorder

Intellectual disability and developmental syndromes

Leukodystrophies and white matter disorders

Lysosomal and storage diseases

Mitochondrial disease

Multi-system genetic syndromes

Neurological diseases

Peroxisomal disorders

Respiratory diseases

Body Systems

Nervous / Sensory

Organs

Brain

Known Genetic Link

Yes, genetic factors contribute to the risk or severity of the condition

Causative Genes

None specified / unknown

Contributory Genes

ARHGEF9

CACNA1H

CDH2

CDKL5

CHRNA4

CLCN4

CLN5

CUX2

DCX

DENND5A

DNM1L

DYRK1A

FMR1

FOXG1

GABRB3

GRIN2B

HCN4

HIVEP2

HNRNPU

IQSEC2

IRF2BPL

KCNB1

KCNQ3

KDM5C

MECP2

MEF2C

MYO9A

PCDH19

PIGA

POLG

PPP3CA

PURA

RDXP2

RYR1

SCN1A

SCN2A

SCN8A

SHANK3

SLC2A1

SLC6A1

SLC6A8

SPTAN1

STXBP1

TSC1/2

USP9X

Type of Inheritance

Autosomal dominant

Autosomal recessive

De novo

Mitochondrial

Not specified / unknown

X-linked dominant

X-linked recessive

Newborn Screening

Not applicable

Disease Mechanism(s)

Aberrant immune response

Abnormal channel regulation

Cell signaling defects

Other

Age of Onset

Early childhood (age 1+-5)

Infancy (age 0-1)

Middle childhood (6-11)

Prebirth

Average Age at Diagnosis

Early childhood (age 1+-5)

Life Expectancy

Adolescence (12-17)

Adulthood (age 18-64)

Early childhood (age 1+-5)

Middle childhood (6-11)

Affected Sex(es)

Female

Male

National Prevalence

10000+

Global Prevalence

10000+

National Incidence

11-50

Global Incidence

11-50

Populations and/or ancestry with higher prevalence

More common in boys than girls.

Symptoms / Phenotypes

behavioral changes

cognitive impairment / confusion / brain fog

developmental delay

seizures / epilepsy

Biomarkers

Diagnostic

· Specific EEG signatures, specific seizure types, intellectual developmental abnormalities

Prognostic

· Specific EEG signatures, specific seizure types, intellectual developmental abnormalities, immune profile

Therapeutic

· Seizure types, specific genes, syndrome types

Existing Therapies

Complementary and Alternative treatments

· Keto/LGI/Atkins/Mod Atkins Diets, Medical Marijuana, many more

Off-Label Drug Use

Regulatory Agency-Approved for Symptom Relief

· Lamotrigine, Rufinamide, Felbamate, Clobazam, Topiramate, CBD, and Fenfluramine are all FDA approved for seizures associated with LGS. Everyone with LGS has epilepsy so there are also more than 40 treatments (drugs, diets, devices, surgeries) that are used to treat seizures in LGS. We try them all.

Therapies in Development

Devices/medical equipment

Repurposed drug

Small molecule therapy (novel small molecule drugs)

Surgical & interventional

Therapeutic Development Stages

IND/CTA submitted but not approved

In clinical trials (Phase I, II, III, or IV)

In preclinical development

In research/exploratory phase

Therapeutic Development Role

Access to registry or natural history study

Data sharing

Focus group participation or coordination

Meetings with regulators (e.g., FDA listening sessions, PFDD meetings)

Outcome measures development

Recruitment and outreach to patients

Recruitment and outreach to trial sites / physicians

Results dissemination (including publications)

Sample provision

Study material design and/or review (not protocol) — includes patient-facing materials such as informed consent

Study protocol design and/or review (includes selection of outcome measures)

Organizational & Research

Cell Lines

None

Cell Lines, Institution

None

Cell Lines, share

N/A

Disease Model

Mouse

Disease Model, Involvement

Consulted

Funded

Disease Model, share

All our disease models are freely available

Organizational Challenges

Funding. Continue to struggle with getting funding from our families who have very sick children. We've tried a number of approaches to get funding from other sources as taught by CCI, but it has been very difficult.

Clinical Trial Role

Data analysis

Data sharing

Focus group

Funding

Meeting with regulators

Outcome measures, development

Recruitment and outreach, patients

Recruitment and outreach, trial sites/physicians

Results dissemination, publication

Study material design, review (not protocol)

Study protocol design, review

Travel coordination

Clinical Trial Types

Observational

Phase 1

Phase 2

Phase 3

Phase 4

Biobank, Institution

None

Center of Excellence, Institution

Cook Children’s Medical Center

Center of Excellence, Involvement

Endorsed/Certified/Accredited

Registry

Yes, we have a registry that we created

Data Collected, Registry

Genetic data

Imaging data

Longitudinal natural history data

Medication usage

Patient contact info

Patient-reported data

Data Entered by, Registry

Other

Platform, Registry

IAMRARE

Natural History Study

Yes, we have a natural history study that we created

Data Collected, Natural History Study

Electronic health records/electronic medical records

Imaging data

Medication usage

Patient-reported outcomes

Retrospective data

Platform, Natural History Study

IAMRARE

FDA Patient Listening Session

FDA Patient-Focused Drug Development (PFDD) Program

Yes

ICD Codes

Yes, we have an ICD-10 code specific to our exact disease

Yes, we have an ICD-11 code specific to our exact disease

Diagnostic Guidelines

Yes, we have guidance available on our website

Science Advisory Board Policies

Yes, willing to share SAB policies

Research Network Policies

Has CRN and willing to share policies

Patient Priority Survey

Yes

Patient Priority Survey, share

Yes, will share

Research Roadmap

Yes we have a Research Roadmap, and will share policies

None

Africa

Asia

Europe

Middle East

North America

South America

Europe