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| {{Infobox medical condition (new) | | {{Short description|A genetic form of epilepsy affecting the frontal lobe}} |
| | name = Autosomal dominant nocturnal frontal lobe epilepsy | | {{Medical condition (new)}} |
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| [[Autosomal_dominant_nocturnal_frontal_lobe_epilepsy|Autosomal dominant nocturnal frontal lobe epilepsy]] (ADNFLE) is an epileptic disorder that results in frequent violent seizures during sleep. The seizures often involve complex motor movements, including hand clenching, arm raising/lowering, and knee bending. Vocalizations, such as shouting, moaning, or crying, are also common. ADNFLE is often misdiagnosed as [[nightmare]]s. The attacks typically occur in clusters and first manifest in childhood. There are four known loci for ADNFLE, with three having known causative genes. These genes, ''CHRNA4'', ''CHRNB2'', and ''CHRNA2'', encode various [[nicotinic acetylcholine receptor]] α and β subunits.
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| == Signs and symptoms ==
| | '''Autosomal dominant nocturnal frontal lobe epilepsy''' (ADNFLE) is a rare [[genetic disorder]] characterized by [[seizures]] that predominantly occur during sleep. This condition is a form of [[epilepsy]] that affects the [[frontal lobe]] of the [[brain]], which is responsible for various functions including movement, decision-making, and problem-solving. |
| ADNFLE is a partial epilepsy disorder characterized by brief violent seizures during sleep. The seizures are complex, involving arm and leg movements, fist clenching, and vocalizations such as yelling and moaning. These seizures often occur in clusters and can first manifest in childhood. Diagnosis is often initially incorrect, with conditions such as [[nightmare]]s, [[night terror]]s, [[parasomnia]]s, and various psychiatric disorders being mistaken for ADNFLE. | |
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| == Causes == | | ==Presentation== |
| While the exact cause of ADNFLE is not well understood, it is believed that malfunction in [[thalamocortical loop]]s plays a vital role in the disorder. This belief is based on three primary factors: the importance of thalamocortical loops in [[sleep]] and the [[frontal cortex]] as the origin of ADNFLE seizures; the fact that both the [[thalamus]] and cortex receive cholinergic inputs and [[acetylcholine receptor]] subunits comprise the three known causative genes for ADNFLE; and the presence of [[K-complex]]es at the start of seizures. It is thought that epilepsy is caused because these receptor subunits are expressed presynaptically by neurons that release the inhibitory transmitter GABA. As a result, the mutation in the α4 subunit could lead to reduced GABA release, causing hyperexcitability.
| | ADNFLE is marked by [[seizures]] that typically occur during the night, often shortly after falling asleep or just before waking. These seizures can manifest as sudden arousals from sleep, often accompanied by complex motor behaviors such as [[thrashing]], [[kicking]], or [[bicycling movements]]. Patients may also experience [[vocalizations]] or [[screaming]] during these episodes. The seizures are usually brief, lasting less than a minute, but can occur multiple times in a single night. |
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| == Pathophysiology == | | ==Genetics== |
| === ''CHRNA4'' ===
| | ADNFLE is inherited in an [[autosomal dominant]] pattern, meaning that a single copy of the altered gene in each cell is sufficient to cause the disorder. Several genes have been associated with ADNFLE, including mutations in the [[CHRNA4]], [[CHRNB2]], and [[CHRNB4]] genes, which encode subunits of the [[nicotinic acetylcholine receptor]]. These mutations can lead to altered receptor function, affecting neuronal excitability and leading to seizures. |
| The first mutation associated with ADNFLE is a [[serine]] to [[phenylalanine]] transition at position 248 (S248F), which is located in the second transmembrane spanning region of the gene encoding a [[nicotinic acetylcholine receptor]] α4 subunit. Receptors containing this mutant subunit are functional, but [[Desensitization (medicine)|desensitize]] at a much faster pace compared to wild-type only receptors. These mutant-containing receptors also recover from desensitization at a much slower rate than wild-type only receptors. These mutant receptors also have a decreased single channel conductance compared to wild-type and have a lower [[Affinity (pharmacology)|affinity]] for [[acetylcholine]]. Importantly, this mutation, along with the others in ''CHRNA4'', produces receptors less sensitive to [[calcium]].
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| Other mutations in ''CHRNA4'' associated with ADNFLE include L259_I260insL, S252L, and T265M, all of which are located in the second transmembrane spanning region. Electrophysiological experiments have shown various effects on receptor sensitivity, desensitization, and calcium permeability as a result of these mutations.
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| === 15q24 ===
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| Some families have been shown to not have mutations in ''CHRNA4'' and, furthermore, to show no [[Genetic linkage|linkage]] around it.
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| ===''CHRNA2''===
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| The third known causative gene for ADNFLE is ''CHRNA2'', which encodes a nicotinic acetylcholine receptor α2 subunit. One mutation identified in ''CHRNA2'' is I279N, which resides in the second transmembrane spanning region. Functional studies of this mutation have shown that receptors containing the I279N mutation display a lower sensitivity to acetylcholine and exhibit altered desensitization kinetics compared to wild-type receptors<ref name="Aridon_2006">{{cite journal |vauthors=Aridon P, Marini C, Di Resta C, Brilli E, De Fusco M, Politi F, Parrini E, Manfredi I, Pisano T, Pruna D, Curia G, Cianchetti C, Pasqualetti M, Becchetti A, Guerrini R, Casari G | title = Increased sensitivity of the neuronal nicotinic receptor alpha 2 subunit causes familial epilepsy with nocturnal wandering and ictal fear. | journal = Am J Hum Genet | volume = 79 | issue = 2 | pages = 342–50 | year = 2006 | pmid = 16826524 | doi = 10.1086/505805 | pmc = 1559477}}</ref>.
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| ==Genetic heterogeneity==
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| Although three causative genes have been identified, there are still families with ADNFLE that do not have mutations in any of these genes. This suggests that there is further genetic heterogeneity in ADNFLE, and more causative genes are yet to be discovered<ref name="Combi_2005">{{cite journal |vauthors=Combi R, Dalprà L, Tenchini ML, Ferini-Strambi L | title = Autosomal dominant nocturnal frontal lobe epilepsy: a critical overview. | journal = J Neurol | volume = 252 | issue = 6 | pages = 663–9 | year = 2005 | pmid = 15999233 | doi = 10.1007/s00415-005-0835-5}}</ref>.
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| ==Diagnosis== | | ==Diagnosis== |
| Diagnosing ADNFLE can be challenging due to its initial presentation, which is often mistaken for nightmares, night terrors, parasomnias, or various psychiatric disorders. A thorough clinical history, including a detailed description of seizure semiology and family history, is essential for an accurate diagnosis. Video-electroencephalogram (video-EEG) monitoring during sleep may also help to capture seizures and confirm the diagnosis. In some cases, genetic testing can be useful to identify mutations in the known causative genes.
| | The diagnosis of ADNFLE is based on clinical evaluation, family history, and [[electroencephalogram]] (EEG) findings. The EEG may show interictal epileptiform discharges, particularly during sleep. Genetic testing can confirm the diagnosis by identifying mutations in the associated genes. |
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| ==Treatment== | | ==Management== |
| Treatment for ADNFLE typically involves the use of antiepileptic drugs (AEDs). The choice of AED may vary depending on the specific seizure characteristics and the individual patient's response to medication. Commonly used AEDs for ADNFLE include carbamazepine, oxcarbazepine, and topiramate. In some cases, other medications such as benzodiazepines, gabapentin, or lamotrigine may also be effective. It is important to work closely with a healthcare professional to determine the most appropriate treatment plan.
| | Management of ADNFLE involves the use of [[antiepileptic drugs]] (AEDs) to control seizures. Commonly used AEDs include [[carbamazepine]], [[oxcarbazepine]], and [[lamotrigine]]. In some cases, lifestyle modifications such as maintaining a regular sleep schedule and avoiding sleep deprivation can help reduce seizure frequency. |
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| ==Prognosis== | | ==Prognosis== |
| The prognosis for individuals with ADNFLE is generally favorable. Most patients experience a significant reduction in seizure frequency and severity with appropriate treatment. Some individuals may even achieve complete seizure control. However, it is important to note that the response to treatment can vary among patients, and some individuals may continue to experience seizures despite medication. In such cases, alternative treatment options or a combination of medications may be considered. It is also worth noting that the severity and frequency of seizures may change over time, with some individuals experiencing improvement as they age. | | The prognosis for individuals with ADNFLE varies. While some patients achieve good seizure control with medication, others may continue to experience frequent seizures. The condition does not typically affect [[intelligence]] or [[cognitive function]], but the impact on sleep can lead to daytime [[fatigue]] and [[sleepiness]]. |
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| ==Cognitive and psychiatric comorbidities==
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| Although the primary symptom of ADNFLE is seizures during sleep, some individuals with the condition may also experience cognitive or psychiatric comorbidities. These can include attention deficit hyperactivity disorder (ADHD), learning difficulties, anxiety, and depression<ref name="Nobili_2012">{{cite journal |vauthors=Nobili L, Proserpio P, Combi R, Provini F, Plazzi G, Bisulli F, Tinuper P, Ferini-Strambi L |title= Nocturnal frontal lobe epilepsy: sleep-related cognitive and behavioral disorders |journal= Epilepsia |volume= 53 |issue= Suppl 1 |pages= 53–9 |year= 2012 |pmid= 22765517 |doi= 10.1111/j.1528-1167.2012.03465.x }}</ref>. In some cases, these comorbidities may have a significant impact on an individual's quality of life and daily functioning. It is essential for healthcare professionals to assess and address these comorbidities as part of the overall treatment plan for individuals with ADNFLE.
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| ==Impact on daily life==
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| ADNFLE can have a significant impact on an individual's daily life, particularly if seizures are not well-controlled. Sleep disturbances due to frequent nocturnal seizures can lead to daytime sleepiness, impaired cognitive function, and reduced quality of life. In addition, the presence of cognitive and psychiatric comorbidities can further complicate daily functioning and social interactions.
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| Early diagnosis and appropriate treatment are essential to minimize the impact of ADNFLE on an individual's daily life. With proper management, many individuals with ADNFLE can achieve good seizure control and maintain a high quality of life.
| | ==Related pages== |
| | * [[Epilepsy]] |
| | * [[Frontal lobe]] |
| | * [[Genetic disorder]] |
| | * [[Seizure]] |
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| ==Summary==
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| Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a rare genetic epilepsy syndrome characterized by sleep-related seizures. It is caused by mutations in the ''CHRNA4'', ''CHRNB2'', and ''CHRNA2'' genes, although additional causative genes may still be undiscovered. Diagnosis can be challenging due to the variable presentation of the condition, but a thorough clinical history, video-EEG monitoring, and genetic testing can aid in accurate diagnosis. Treatment typically involves the use of antiepileptic drugs, and the prognosis is generally favorable with appropriate treatment. Early diagnosis and management are essential to minimize the impact of ADNFLE on an individual's daily life and overall well-being.
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| ==Further reading==
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| * [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=adnfle GeneReviews/NCBI/NIH/UW entry on Autosomal Dominant Nocturnal Frontal Lobe Epilepsy]
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| == External links ==
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| | OMIM_mult = {{OMIM|603204||none}} {{OMIM|605375||none}} {{OMIM|610353||none}}
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| {{DEFAULTSORT:Autosomal Dominant Nocturnal Frontal Lobe Epilepsy}}
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| [[Category:Epilepsy types]] | | [[Category:Epilepsy types]] |
| [[Category:Sleep disorders]] | | [[Category:Genetic disorders]] |
| [[Category:Channelopathies]] | | [[Category:Neurology]] |
| [[Category:Unsolved problems in neuroscience]]
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| [[Category:Frontal lobe]]
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A genetic form of epilepsy affecting the frontal lobe
Template:Medical condition (new)
Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a rare genetic disorder characterized by seizures that predominantly occur during sleep. This condition is a form of epilepsy that affects the frontal lobe of the brain, which is responsible for various functions including movement, decision-making, and problem-solving.
Presentation
ADNFLE is marked by seizures that typically occur during the night, often shortly after falling asleep or just before waking. These seizures can manifest as sudden arousals from sleep, often accompanied by complex motor behaviors such as thrashing, kicking, or bicycling movements. Patients may also experience vocalizations or screaming during these episodes. The seizures are usually brief, lasting less than a minute, but can occur multiple times in a single night.
Genetics
ADNFLE is inherited in an autosomal dominant pattern, meaning that a single copy of the altered gene in each cell is sufficient to cause the disorder. Several genes have been associated with ADNFLE, including mutations in the CHRNA4, CHRNB2, and CHRNB4 genes, which encode subunits of the nicotinic acetylcholine receptor. These mutations can lead to altered receptor function, affecting neuronal excitability and leading to seizures.
Diagnosis
The diagnosis of ADNFLE is based on clinical evaluation, family history, and electroencephalogram (EEG) findings. The EEG may show interictal epileptiform discharges, particularly during sleep. Genetic testing can confirm the diagnosis by identifying mutations in the associated genes.
Management
Management of ADNFLE involves the use of antiepileptic drugs (AEDs) to control seizures. Commonly used AEDs include carbamazepine, oxcarbazepine, and lamotrigine. In some cases, lifestyle modifications such as maintaining a regular sleep schedule and avoiding sleep deprivation can help reduce seizure frequency.
Prognosis
The prognosis for individuals with ADNFLE varies. While some patients achieve good seizure control with medication, others may continue to experience frequent seizures. The condition does not typically affect intelligence or cognitive function, but the impact on sleep can lead to daytime fatigue and sleepiness.
Related pages
