Epilepsy-aphasia spectrum ..., (Epilepsy-aphasia spectrum) - Gen GRIN2A

The spectrum of epilepsy-aphasia (FESD), also known as focal epilepsies with impaired speech and language, is a group of diseases that have signs and symptoms overlap. A key feature of these processes is the deterioration of language skills (aphasia). Language problems can affect speech, reading and writing. Another common feature of the spectrum of epilepsy-aphasia are certain patterns of abnormal electrical activity in the brain, which can be detected by an electroencephalogram (EEG). Many people who show signs of this spectrum develop epilepsy and, in some individuals, from mild to severe intellectual disabilities.

The processes included in the spectrum of epilepsy-aphasia, all of which begin in childhood, include: the Landau-Kleffner syndrome (LKS), syndrome epileptic encephalopathy with spike wave continues during sleep (ECSWS), epilepsy rolandic autosomal dominant with speech dyspraxia (ADRESD), epilepsy-aphasia intermediate (IEAD), atypical childhood epilepsy with center points (ACECTS), and childhood epilepsy with center points (CECTS).

LKS and ECSWS are at the severe end of the spectrum. Both syndromes are characterized by an abnormal pattern of electrical activity in the brain known as peak and continuous waves during slow wave sleep (CSWS). This pattern occurs while the child is sleeping affected, specifically during deep sleep (slow wave). Most children with LKS develop normally in early childhood, although some develop speech later than their peers. However, affected children lose language skills around 5 years. This loss usually starts with verbal agnosia. As the syndrome LKS develops the ability to express speech is also affected. Approximately 70% of children with LKS having convulsions, generally described as a type of focal (or partial) because the seizure activity occurs in specific brain regions rather than affect the entire brain.

Meanwhile, about half of children with ECSWS develop normally in early childhood, while others suffer delayed development of motor skills and speech. Although children with ECSWS often lose a number of previously acquired skills (including those involved in language, movement, learning or behavior), not all individuals with ECSWS suffering from aphasia. Seizures occur in approximately 80% of children with ECSWS and may include a variety of types, such as atypical absence seizures, hemiclónicas seizures, or tonic-clonic seizures.

Furthermore, CECTS is mild end of the spectrum of epilepsy-aphasia. Rolandic affected children suffer seizures, which are caused by abnormal activity in a brain area called the rolandic region. Convulsions, which usually occur during sleep, causing twitching and numbness or tingling in the face or tongue. In most people with CECTS, seizures disappear at the end of adolescence. Individuals most affected develop normally, although some express dyspraxia or deterioration of language skills.

The other processes spectrum epilepsy-aphasia are less frequent and moderate in severity. IEAD children usually show a developmental delay or regression of language skills. Some suffer seizures and most have abnormal electrical activity in the brain during sleep, although not prominent enough to be classified as a CSWS. ACECTS is characterized by seizures and developmental regression that can affect movement, language and attention. ACECTS have children with abnormal electrical activity in the brain sometimes classified as a CSWS. Finally, ADRESD is characterized by focal seizures, speech difficulties due to dyspraxia and learning problems.

All the processes described above and encompassed within the spectrum of epilepsy-aphasia, may be due to mutations in the gene GRIN2A (NMDA ionotropic glutamate receptor subunit type 2A). These mutations are more common in severe processes; They found in up to 20 percent of people with LKS or ECSWS and about 5 percent of people with CECTS. In affected individuals without a genetic mutation GRIN2A, the cause of the disease is unknown. It is likely that changes in other unidentified genes may also be associated with epilepsy-spectrum processes aphasia.

The GRIN2A gene, located on the short arm of chromosome 16 (16p13.2), encoding the protein GluN2A (formerly known as NR2A). This protein is found in neurons in the brain and spinal cord, including brain regions involved in speech and language. The GluN2A protein is a subunit of a subset of NMDA receptors. NMDA receptors are ion channels glutamate. When glutamate and glycine receptor binding, a channel is opened, allowing ions to flow. Ion flux generates currents that activate neurons to send signals to the brain. NMDA receptors are involved in normal brain development, synaptic plasticity, learning and memory. Also they appear to play a role during deep sleep (slow wave). The GluN2A subunit of NMDA receptors determines which part of the brain receptor is and how it works. The site also provides that binds glutamate.

There are more than 50 mutations in the gene GRIN2A in some people with epilepsy processes spectrum-aphasia. Most mutations result GRIN2A gene synthesis of a nonfunctional protein GluN2A or inhibit protein coding. These mutations probably cause a deficiency of NMDA receptors containing the GluN2A subunit. It is believed that as a result, signaling occurs through other types of NMDA receptors more easily activate neurons, leading to excessive signaling in the brain. Other mutations result in protein synthesis GluN2A abnormal likely altering how they act receptors, possibly increasing signaling. Excessive activity of neurons in the brain can lead to seizures, other abnormal brain activity and death of neurons. GluN2A changes specifically affect signaling in brain regions involved in speech and language and alter brain activity during slow - wave sleep, leading to several of the signs and symptoms of this group of diseases. It is unclear why some mutations of genes GRIN2A cause relatively mild illness and others cause more severe signs and symptoms.

Spectrum processes epilepsy-aphasia are inherited in an autosomal dominant pattern, which means that a copy of the altered gene in each cell is sufficient to express the disease. Individuals affected by the specter of epilepsy-aphasia may have family members with a disease spectrum of epilepsy-related aphasia or alteration, as isolated seizures or speech and language. In some cases, an affected person inherits the mutation from an affected parent. Other cases are due to new mutations in the gene and occur in people with no history of disease in your family.

Tests in IVAMI: in IVAMI perform detection of mutations associated with epilepsy spectrum-aphasia, by complete PCR amplification of exons GRIN2A gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).