Lennox-Gastaut syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Lennox-Gastaut syndrome is a severe condition characterized by repeated seizures (epilepsy) that begin early in life. Affected individuals have multiple types of seizures, developmental delays, and particular patterns of brain activity measured by a test called an electroencephalogram (EEG). An EEG shows a slow spike-and-wave pattern during wakefulness and generalized paroxysmal fast activity during sleep.

In people with Lennox-Gastaut syndrome, epilepsy begins in early childhood, usually between ages 3 and 5. The most common seizure type is tonic seizures, which cause the muscles to stiffen (contract) uncontrollably. These seizures typically occur during sleep; they may also occur during wakefulness. Also common are atonic seizures, which are caused by a sudden loss of muscle tone. Tonic and atonic seizures can cause sudden falls that can result in serious or life-threatening injuries. Additionally, many affected individuals have atypical absence seizures, which cause a very brief partial or complete loss of consciousness. Other types of seizures have been reported less frequently in people with Lennox-Gastaut syndrome. Seizures associated with Lennox-Gastaut syndrome often do not respond well to therapy with anti-epileptic medications.

Although each seizure episode associated with Lennox-Gastaut syndrome is usually brief, more than two-thirds of affected individuals experience prolonged periods of seizure activity (known as status epilepticus) or episodes of many seizures that occur in a cluster.

About one-third of people with Lennox-Gastaut syndrome have normal intellectual development before seizures begin. The remainder have intellectual disability or learning problems even before seizures arise. Intellectual problems may worsen over time, particularly if seizures are very frequent or severe. Some affected children develop additional neurological abnormalities and behavioral problems. Many are also slow to develop motor skills such as sitting and crawling. As a result of their seizures and intellectual disability, most people with Lennox-Gastaut syndrome require help with daily activities. However, a small percentage of affected adults can live independently.

People with Lennox-Gastaut syndrome have a higher risk of death than their peers of the same age. Although the increased risk is not fully understood, it is partly due to poorly controlled seizures, pneumonia resulting from inhaling saliva (aspiration pneumonia) during a seizure, and injuries from falls. In addition, individuals with Lennox-Gastaut syndrome are at risk of sudden unexpected death in epilepsy (SUDEP), which describes sudden death with no known cause in someone with epilepsy; it is not the direct result of a seizure.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Lennox-Gastaut syndrome can have many different causes. The disorder likely has a genetic component, although the specific genetic factors are not well understood.

Most cases of Lennox-Gastaut syndrome develop from an existing neurological abnormality. These cases maybe be caused by brain injuries that occur before or during birth, problems with blood flow in the developing brain, brain infections, or other disorders affecting the nervous system. The condition can also arise from brain malformations such as forms of cortical dysplasia, which are abnormalities in the outer surface of the brain (cerebral cortex). Many people with Lennox-Gastaut syndrome have a history of epilepsy beginning in infancy (infantile spasms) or a related condition called West syndrome before developing the features of Lennox-Gastaut syndrome. It is not clear why these neurological abnormalities evolve into Lennox-Gastaut syndrome.

In addition, variants (also called mutations) in several genes have been associated with Lennox-Gastaut syndrome, each in a small number of affected individuals. These genes are involved in the function of nerve cells in the brain, but it is unclear how changes in them contribute to the development of Lennox-Gastaut syndrome. The condition can also occur as part of a genetic disorder, such as tuberous sclerosis complex.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Most cases of Lennox-Gastaut syndrome are sporadic, which means they occur in people with no history of the disorder in their family. When Lennox-Gastaut syndrome is associated with a genetic change, the variant is usually not inherited but occurs as a random (de novo) event during the formation of reproductive cells (eggs or sperm) in an affected person's parent or during early embryonic development. However, 3 to 30 percent of people with this condition have a family history of some type of epilepsy, indicating that inherited genetic factors may play a role in some cases of Lennox-Gastaut syndrome.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Lennox-Gastaut syndrome affects an estimated 1 to 2 per million people worldwide. This condition accounts for 3 to 4 percent of cases of epilepsy in children and 1 to 2 percent of cases in adults. For unknown reasons, it appears to be more common in males than in females.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

EEG with focal sharp slow waves · Very frequent (99-80%)

EEG with focal sharp transient waves of a duration between 80 and 200 msec followed by a slow wave.

Encephalopathy · Very frequent (99-80%)

Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state.

Intellectual disability · Very frequent (99-80%)

The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence.

Abnormal brainstem morphology · Frequent (79-30%)

An anomaly of the brainstem.

Aggressive behavior · Frequent (79-30%)

Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires).

Atonic seizure · Frequent (79-30%)

Atonic seizure is a type of motor seizure characterized by a sudden loss or diminution of muscle tone without apparent preceding myoclonic or tonic event lasting about 1 to 2 seconds, involving head, trunk, jaw, or limb musculature.

Atypical absence seizure · Frequent (79-30%)

An atypical absence seizure is a type of generalized non-motor (absence) seizure characterized by interruption of ongoing activities and reduced responsiveness. In comparison to a typical absence seizure, changes in tone may be more pronounced, onset and/or cessation may be less abrupt, and the duration of the ictus and post-ictal recovery may be longer. Although not always available, an EEG often demonstrates slow (<3 Hz), irregular, generalized spike-wave activity.

Atypical behavior · Frequent (79-30%)

Atypical behavior is an abnormality in a person's actions that can be controlled or modulated by the will of the individual. While abnormal behaviors can be difficult to control, they are distinct from other abnormal actions that cannot be affected by the individual's will.

Other findings in the same source

From: Orphanet

Additional reported features include Autistic behavior (Frequent (79-30%)); Bilateral tonic-clonic seizure (Frequent (79-30%)); EEG abnormality (Frequent (79-30%)); Generalized tonic seizure (Frequent (79-30%)); Hyperactivity (Frequent (79-30%)); Irritability (Frequent (79-30%)); Mental deterioration (Frequent (79-30%)); Myoclonus (Frequent (79-30%)); Neurodevelopmental delay (Frequent (79-30%)); Personality disorder (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Lennox-Gastaut syndrome is Neurology, with a neurologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which nervous-system findings help explain the symptoms?
• Would an assessment of walking, communication or daily function be helpful?
• Are rehabilitation or other specialist services relevant?

Treatment discussions and follow-up

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.