What causes LGS?

In LGS, the brain is affected at a critical time in its development. Learning problems and seizures result.

There are many causes of seizures that can evolve into LGS. While we don’t know why seizures evolve into LGS, we do know that finding the cause of seizures requires extensive testing. In some cases, more than one cause may be found.

Causes of LGS may include:

An altered brain structure is the most common cause of LGS. MRI, or magnetic resonance imaging, can detect altered brain structure. Brain structure can be affected by:

Abnormal development. This occurs when the baby is still in the womb. Often, the cause of it is unknown. However, it can result from:
  • Infection during pregnancy
  • Genetic abnormality
Brain injury early in life. Various types of brain injury early in life can result in LGS:
  • Low oxygen or blood flow to the brain (e.g. Hypoxic Ischemia or HIE)
  • Brain infection (e.g. meningitis, encephalitis)
  • Traumatic brain injury (e.g. stroke)
  • Early brain radiation
Genetic differences are important causes of early childhood epilepsy. Some types of genetic changes result in abnormal brain development that can be seen on MRI.

In other cases, genetic causes result in changes that occur at a microscopic level. This can change how the brain functions. In these cases, the brain MRI is usually normal.

Several lab tests can look for genetic causes. However, genetic testing can have implications for relatives. Therefore, families should receive counseling prior to genetic testing.

Learn more about Genetic Testing
Metabolic causes of LGS are rare. Still, they are important to consider. There are many types of metabolic disorders. They usually relate to difficulty breaking down nutrients in the body. They cause symptoms due to:
  • A lack of essential nutrients to keep brain cells healthy
  • A toxic buildup that results in brain cell dysfunction
Some of these conditions have specific treatments. Early recognition can prevent further brain injury. Metabolic disorders can be diagnosed with lab tests. These usually include blood, urine, and spinal fluid tests. Some can be detected in genetic tests.
Infections are a rare cause of LGS.
  • Prenatal infection. Viruses can infect the fetus during pregnancy. Blood tests and eye exams can usually detect prenatal infection.
  • Brain infection early in life. Brain infections can lead to brain injury and a severe seizure disorder like LGS.
Some epilepsies result from the body creating abnormal proteins or antibodies. They can cause injury to the brain. This is an exceedingly rare cause of LGS. When seizures begin suddenly following illness or vaccination, this can be considered. It is detected in blood and spinal fluid tests.

Is the MRI normal in those with LGS?

About 2 out of 3 of those with LGS have abnormal brain imaging at the time of diagnosis. Having an abnormal MRI is often associated with a poorer LGS outcome. 

Can LGS evolve from other epilepsy syndromes?

Yes, LGS can also develop from other epilepsy syndromes such as West Syndrome, Tuberous Sclerosis Complex, and Ohtahara Syndrome. 

The risk factors for developing LGS include:

  • Early life seizures that are treatment-resistant
  • Structural abnormalities are seen on the MRI
  • Brain injuries at birth or in early childhood (e.g., lack of oxygen, stroke, tumors)
  • Mutations in any of the more than 150 epilepsy-related genes (e.g., TSC1, SCN2A, SCN1A, CDKL5, Dup15q, Trisomy 21, FOXG1 Dup, SIK1, GRIN2A, and many more)
  • Infantile spasms
  • The presence of more than one seizure type
  • Epileptic encephalopathy syndromes such as West, Ohtahara, etc. 
  • Developmental slowing or regression
  • Failure of >2 anti-seizure treatments

Having all of these risk factors does not mean someone will develop LGS. It means they are at high risk of developing LGS. We do not know why some with these risk factors develop LGS, and some do not. 

Watch: Causes of LGS and What They Mean

2019 LGS Foundation Family Conference in Seattle, Washington, Tracy Dixon Salazar, Ph.D. – CAUSES OF LGS AND WHAT THEY MEAN


Thank you to the Child Neurology Foundation for allowing us to adapt this article for this site.

Authors: Shaun Ajinkya, MD; Elaine Wirrell, MD,  Mayo Clinic – Rochester, Minnesota Reviewed: April 2021 

The information here is not intended to provide diagnosis, treatment, or medical advice and should not be considered a substitute for advice from a healthcare professional. The content provided is for informational purposes only. LGSF is not responsible for actions taken based on the information included on this webpage. Please consult with a physician or other healthcare professional regarding any medical or health related diagnosis or treatment options.

Updated 7/11/2023