What is Lennox-Gastaut syndrome?
Lennox-Gastaut syndrome (LGS) is a severe form of epilepsy with seizures that begin in early childhood, usually between the ages of 2 and 5, and continue into adulthood. About 10% to 30% of children with LGS have a prior history of earlier onset epilepsy syndromes, such as West syndrome or Ohtahara syndrome. LGS accounts for 3% to 4% of all children with epilepsy.
Children with LGS experience multiple types of seizures that are often resistant to many types of antiseizure medications. These may include:
- Tonic (stiffening) seizures, especially in sleep
- Atonic (drop) seizures
- Atypical absence seizures
- Myoclonic seizures (sudden muscle jerks)
- Generalized tonic-clonic seizures (also called grand mal seizures)
Many children with the condition have developmental delays, cognitive impairments or behavioral problems. These problems may be noticed before the first appearance of seizures.
Causes of Lennox-Gastaut syndrome
In many cases (approximately 70%), Lennox-Gastaut syndrome is secondary to an identifiable cause. These causes include structural brain differences caused by an acquired brain injury or infection, genetic syndromes that cause differences in brain development, or hereditary metabolic disorders.
In a quarter to a third of cases, no cause can be identified. Genetic causes likely account for a majority of unexplained LGS.
Diagnosis of Lennox-Gastaut syndrome
The appearance of multiple types of seizures in early childhood, particularly a combination of tonic, atonic and atypical absence seizures, is a key diagnostic indicator of Lennox-Gastaut syndrome. The presence of developmental delays, cognitive impairments or behavioral problems might support the diagnosis.
When Lennox-Gastaut syndrome is suspected, additional tests may be done to confirm a diagnosis, including:
- Electroencephalogram (EEG), which may detect a characteristic pattern of abnormal brain activity called slow spike-and-wave activity
- Magnetic resonance imaging (MRI) to look for structural brain abnormalities
Genetics of Lennox-Gastaut syndrome
Many genes have been identified that are associated with Lennox-Gastaut syndrome, and in almost all cases the mutation in the child with LGS has occurred spontaneously (de novo) and was not inherited from either parent. Some genes that can cause LGS include pathogenic variants in CDKL5, DNM1, STXBP1, or SCN2A. However, over 50 individual genes have been identified so far. In most cases a single gene is affected. In about 5% of children with unexplained LGS, larger pieces of DNA are missing or extra (microdeletions or microduplications) that affect multiple genes. Genetic testing, including epilepsy panel testing or whole exome sequencing, is able to identify a positive genetic diagnosis in up to 40% of children with unexplained LGS.
Treatment for Lennox-Gastaut syndrome
The primary goal of Lennox-Gastaut syndrome treatment is to reduce or eliminate the seizures. Lennox-Gastaut syndrome is considered an epileptic encephalopathy, a condition in which the epileptic seizures can directly contribute to cognitive and behavioral impairments. In some cases, information provided by genetic testing can help guide treatment or medical management decisions.
The seizures in Lennox-Gastaut syndrome can be difficult to control, as they often don’t respond to anti-epileptic medications.
- A combination of anti-seizure medications to control the different seizure types may help to provide partial relief.
- Rescue therapies, a different set of medications, may be given to help stop or shorten clusters of seizures when they occur.
- Implantable devices such as Vagus Nerve Stimulation (VNS) or Responsive Neurostimulation (RNS) may be considered when medications are not effective in controlling seizures.
- Dietary therapy, such as the ketogenic diet, may be helpful in some cases.
- Corpus callosotomy surgery to separate the two halves of the brain may be effective for atonic seizures, tonic clonic seizures, and tonic seizures and may significantly reduce seizure frequency and duration in patients with LGS.
Family training and support is a key element in a successful treatment plan. Parents and caregivers must know how to watch for and respond to seizures.
Lennox-Gastaut syndrome treatment will generally include physical therapy, occupational therapy and speech therapy. School-age children are usually placed in a special education classroom or receive home tutoring.
Long-term outlook for Lennox-Gastaut syndrome
The long-term outlook for children with Lennox-Gastaut syndrome varies widely, but complete recovery with freedom from seizures is rare. Most children have some level of permanent cognitive impairment. Roughly half have ongoing behavioral problems.
Seizures typically continue through childhood and into adulthood, with the type and frequency of the seizures changing over time. Regular medical care is needed to adjust treatment to changing seizure patterns.
Children and adults with Lennox-Gastaut syndrome are at an increased risk of premature mortality, often from sudden unexpected death in epilepsy (SUDEP), injury, seizures, or as a consequence of the underlying brain disorder.
Why choose CHOP for Lennox-Gastaut syndrome treatment?
The Epilepsy Neurogenetics Initiative (ENGIN) at Children’s Hospital of Philadelphia (CHOP) integrates genetic testing into the diagnosis and treatment of children with difficult-to-treat or unexplained epilepsies, genetic epilepsy syndromes and other genetic neurodevelopmental disorders. We combine cutting-edge clinical care and advanced genetic testing with innovative research to identify the underlying cause of a child’s epilepsy and develop an individualized approach to treatment and management.
Families come to our ENGIN clinic from all over the world. Through ENGIN, your child will have access to any other medical specialists they may need, as well as a full range of epilepsy therapies provided through CHOP’s Pediatric Epilepsy Program, including medication, dietary treatment and epilepsy surgery, as well as ongoing follow-up care.
