Frequency
The prevalence of the epilepsy-aphasia spectrum is unknown. Most of the conditions in the spectrum are rare; however, CECTS is one of the most common forms of epilepsy in children, accounting for 8 to 25 percent of cases. It is estimated to occur in 1 in 5,000 children younger than 16.
Causes
Variants (also known as mutations) in the GRIN2A gene can cause conditions in the epilepsy-aphasia spectrum. These variants are more common in the more severe conditions; they are found in up to 20 percent of people with LKS or ECSWS and about 5 percent of people with CECTS. In affected people without a GRIN2A gene variant, the cause of the condition is unknown. Some affected individuals have a brain abnormality that may contribute to the condition. Researchers suspect that changes in other, unidentified genes may also be associated with epilepsy-aphasia spectrum disorders.
The GRIN2A gene provides instructions for making the GluN2A protein, which is one component (subunit) of a subset of NMDA receptors. NMDA receptors transmit signals that turn on nerve cells (neurons) in the brain. Signaling through these receptors is involved in normal brain development, changes in the brain in response to experience (synaptic plasticity), learning, and memory. The GluN2A subunit determines where in the brain the receptor is located and how it functions. Receptors containing this subunit are found in regions of the brain involved in speech and language, among other regions. These receptors also appear to play a role in brain signaling during slow-wave sleep.
Variants in the GRIN2A gene lead to altered NMDA receptor signaling in the brain. As a result, neurons may be abnormally turned on, which can cause seizures and other abnormal brain activity and may lead to death of the neurons. Changes in GluN2A appear to particularly affect signaling in regions of the brain involved in speech and language and disrupt brain activity during slow-wave sleep, leading to several of the signs and symptoms of this group of conditions.
It is not clear why some people with a GRIN2A gene variant have a relatively mild condition and others have more severe signs and symptoms, even within the same family. Variations in other genes and environmental factors may also play a role in development of the condition.
Inheritance
Conditions in the epilepsy-aphasia spectrum that are caused by GRIN2A gene variants are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Individuals with an epilepsy-aphasia spectrum disorder may have family members with a condition in the epilepsy-aphasia spectrum or a related disorder such as isolated seizures or speech and language problems.
In some cases, an affected person inherits the variant from one affected parent. Other cases result from new variants in the gene
and occur in people with no history of the disorder in their family.
Other Names for This Condition
- Acquired aphasia with epilepsy
- DEE/EE-SWAS
- Developmental and/or epileptic encephalopathy with spike-wave activation in Sleep
- Epilepsy with continuous spike-wave in sleep
- Epilepsy with electrographic status epilepticus in sleep
- FESD
- Focal epilepsies with speech and language disorders
- Focal epilepsy with speech disorder and with or without mental retardation
Additional Information & Resources
Genetic and Rare Diseases Information Center
Patient Support and Advocacy Resources
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
References
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