Nocturnal frontal lobe epilepsy autosomal dominant (autosomal dominant nocturnal frontal lobe epilepsy -ADNFLE-) - Genes CHRNA2, CHRNA4 and CHRNB2.
Nocturnal frontal lobe epilepsy autosomal dominant (ADNFLE) is a rare form of epilepsy that occurs in families. This alteration causes seizures usually occur at night while the victim is sleeping, although some people also have seizures during the day. ADNFLE own seizures tend to occur in groups. Each episode lasts from a few seconds to a few minutes. Lie that some people have mild seizures that simply make you wake from their sleep, others have more severe episodes that may include sudden and repetitive movements of the arms and legs. Sometimes the person can get out of bed and walk, which can be confused with sleepwalking. The person may also cry out , panting, grunting or emit other sounds. Often these episodes are misdiagnosed as nightmares, night terrors, or panic attacks.
Often in some types of epilepsy, including ADNFLE, a pattern of neurological symptoms called aura precedes an attack. The most common symptoms associated with an aura in people with ADNFLE are tingling, chills, a feeling of fear, dizziness and a feeling of falling or being pushed. Some affected individuals have also expressed a feeling of shortness of breath, hyperventilation or suffocation. Although it is unclear the trigger of these events, it is likely that may be due to stress or fatigue, however, in most cases seizures have recognized triggers.
Seizures associated with ADNFLE can start at any time from childhood to middle adulthood, but most cases are manifested in childhood. The episodes tend to be milder and less frequent with age. In the most affected, seizures can be controlled effectively with medication. Most people are intellectually normal, and no problems with brain function between seizures. However, some people have expressed psychiatric disorders (such as schizophrenia), behavioral problems or intellectual disabilities. It is unclear whether these additional features are directly related to epilepsy in these individuals.
This process is due to mutations in genes CHRNA2, located on the short arm of chromosome 8 (8p21), CHRNA4, located on the long arm of chromosome 20 (20q13.33) or CHRNB2, located on the long arm of chromosome 1 ( 1q21.3). These genes encode subunits ?2, ?4 and ?2, respectively, of a larger molecule receptor neuronal nicotinic acetylcholine (nAChR) called. This receptor plays an important role in chemical signaling between neurons in the brain. Communication between neurons depends on neurotransmitters that are released from one neuron and taken up by neighboring neurons. Each nAChR protein comprises a combination of five subunits, usually two alpha subunits (?) and three beta subunits (?). Many different combinations are possible, and the characteristics of each protein depends on what nAChR subunits composed. In the brain, proteins are widely distributed and nAChR play an important role in chemical signaling between neurons. Proteins act as channels, allowing the charged atoms including calcium, sodium, and potassium, traverse the cell membrane. These channels are open when connected to a brain chemical called acetylcholine. The channels also open in response to nicotine, the addictive substance in snuff. A wide range of brain functions rely on nAChR channels, including sleep and wakefulness, fatigue, anxiety, attention, pain perception and memory. The channels are also active before birth, suggesting that they are involved in brain development.
They have identified at least one mutation in the gene CHRNA2, 4 mutations in the gene CHRNA4 and 3 CHRNB2 gene mutations in people with nocturnal frontal lobe epilepsy autosomal dominant (ADNFLE). Most of these mutations change amino acids in the protein causing the channels more easily than usual open. As a result, it increases the flow of ions across the cell membrane altering the release of neurotransmitters, which alters the signaling between neurons. It is believed that mutations in these genes affect the normal release and absorption of certain neurotransmitters in the brain. The resulting changes in signaling between neurons probably trigger the abnormal brain activity associated with seizures. Seizures associated with ADNFLE begin in the frontal lobe. These brain regions are involved in many critical functions, including reasoning, planning, judgment and problem solving. It is unclear why mutations in these genes cause seizures in the frontal lobes, more than in other parts of the brain. ADNFLE genetic cause has been identified in only a small percentage of the affected families. In some cases, a different gene that make up the nAChR is involved. In the remaining families, the cause of the disturbance is unknown.
This disease is inherited as an autosomal dominant pattern, meaning that one copy of the altered gene in each cell is sufficient to increase the risk of developing epilepsy. About 70% of people who inherit a mutation in the CHRNA2, CHRNA4 or CHRNB2 will develop seizures. In most cases, an affected person has an affected parent and other relatives with the disease. Other cases are described as sporadic, meaning that an affected person has no family history of the disorder.
Tests in IVAMI: in IVAMI perform the detection of mutations associated with nocturnal frontal lobe epilepsy autosomal dominant (ADNFLE), by complete PCR amplification of the exons of CHRNA2, CHRNA4 and CHRNB2 genes, respectively, 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).