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Autosomal dominant nocturnal frontal lobe epilepsy 1(ENFL1)

MedGen UID:
324932
Concept ID:
C1838049
Disease or Syndrome
Synonyms: CHRNA4-Related Nocturnal Frontal Lobe Epilepsy, Autosomal Dominant; Epilepsy, nocturnal frontal lobe, type 1
 
Gene (location): CHRNA4 (20q13.33)
 
Monarch Initiative: MONDO:0010899
OMIM®: 600513

Disease characteristics

Autosomal dominant sleep-related hypermotor (hyperkinetic) epilepsy (ADSHE) is a seizure disorder characterized by clusters of nocturnal motor seizures that are often stereotyped and brief (<2 minutes). They vary from simple arousals from sleep to dramatic, often hyperkinetic events with tonic or dystonic features. Affected individuals may experience an aura. Retained awareness during seizures is common. A minority of individuals experience daytime seizures. Age of onset ranges from infancy to adulthood. About 80% of individuals develop ADSHE in the first two decades of life; mean age of onset is ten years. Clinical neurologic examination is normal and intellect is usually preserved, but reduced intellect, psychiatric comorbidities, or cognitive deficits may occur. Within a family, the manifestations of the disorder may vary considerably. ADSHE is lifelong but not progressive. As an individual reaches middle age, seizures may become milder and less frequent. [from GeneReviews]
Authors:
Hirokazu Kurahashi  |  Shinichi Hirose   view full author information

Additional descriptions

From OMIM
Autosomal dominant nocturnal frontal lobe epilepsy (ENFL, ADNFLE) is a partial epilepsy with frontal lobe seizure semiology. It is characterized by childhood onset of frequent violent and brief motor seizures occurring at night. The disorder may be misdiagnosed as night terrors, nightmares, hysteria, or paroxysmal nocturnal dystonia. The condition usually persists through adult life (Scheffer et al., 1994, 1995). The disorder is clinically distinctive and relatively homogeneous, although seizure severity and specific frontal lobe seizure manifestations vary within families (Hayman et al., 1997). Genetic Heterogeneity of Nocturnal Frontal Lobe Epilepsy Nocturnal frontal lobe epilepsy is a genetically heterogeneous condition. See also ENFL2 (603204), which maps to chromosome 15q24; ENFL3 (605375), caused by mutation in the CHRNB2 gene (118507) on chromosome 1q21; ENFL4 (610353), caused by mutation in the CHRNA2 gene (118502) on chromosome 8p21; and ENFL5 (615005), caused by mutation in the KCNT1 gene (608167) on chromosome 9q34. Nocturnal frontal lobe seizures are also observed in some patients with familial focal epilepsy with variable foci (FFEVF; 604364), caused by mutation in the DEPDC5 gene (614191) on chromosome 22q12.  http://www.omim.org/entry/600513
From MedlinePlus Genetics
The seizures associated with ADNFLE can begin anytime from infancy to mid-adulthood, but most begin in childhood. The episodes tend to become milder and less frequent with age. In most affected people, the seizures can be effectively controlled with medication.

In some types of epilepsy, including ADNFLE, a pattern of neurological symptoms called an aura often precedes a seizure. The most common symptoms associated with an aura in people with ADNFLE are tingling, shivering, a sense of fear, dizziness (vertigo), and a feeling of falling or being pushed. Some affected people have also reported a feeling of breathlessness, overly fast breathing (hyperventilation), or choking. It is unclear what brings on seizures in people with ADNFLE. Episodes may be triggered by stress or fatigue, but in most cases the seizures do not have any recognized triggers.

The seizures characteristic of ADNFLE tend to occur in clusters, with each one lasting from a few seconds to a few minutes. Some people have mild seizures that simply cause them to wake up from sleep. Others have more severe episodes that can include sudden, repetitive movements such as flinging or throwing motions of the arms and bicycling movements of the legs. The person may get out of bed and wander around, which can be mistaken for sleepwalking. The person may also cry out or make moaning, gasping, or grunting sounds. These episodes are sometimes misdiagnosed as nightmares, night terrors, or panic attacks.

Most people with ADNFLE are intellectually normal, and there are no problems with their brain function between seizures. However, some people with ADNFLE have experienced psychiatric disorders (such as schizophrenia), behavioral problems, or intellectual disability. It is unclear whether these additional features are directly related to epilepsy in these individuals.

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is an uncommon form of epilepsy that runs in families. This disorder causes seizures that usually occur at night (nocturnally) while an affected person is sleeping. Some people with ADNFLE also have seizures during the day.  https://medlineplus.gov/genetics/condition/autosomal-dominant-nocturnal-frontal-lobe-epilepsy

Clinical features

From HPO
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Focal-onset seizure
MedGen UID:
199670
Concept ID:
C0751495
Disease or Syndrome
A focal-onset seizure is a type of seizure originating within networks limited to one hemisphere. They may be discretely localized or more widely distributed, and may originate in subcortical structures.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.

Recent clinical studies

Etiology

Conti V, Aracri P, Chiti L, Brusco S, Mari F, Marini C, Albanese M, Marchi A, Liguori C, Placidi F, Romigi A, Becchetti A, Guerrini R
Neurology 2015 Apr 14;84(15):1520-8. Epub 2015 Mar 13 doi: 10.1212/WNL.0000000000001471. PMID: 25770198Free PMC Article
Ishida S, Picard F, Rudolf G, Noé E, Achaz G, Thomas P, Genton P, Mundwiller E, Wolff M, Marescaux C, Miles R, Baulac M, Hirsch E, Leguern E, Baulac S
Nat Genet 2013 May;45(5):552-5. Epub 2013 Mar 31 doi: 10.1038/ng.2601. PMID: 23542701Free PMC Article
Naldi I, Bisulli F, Vignatelli L, Licchetta L, Pittau F, Di Vito L, Mostacci B, Menghi V, Provini F, Montagna P, Tinuper P
Epilepsy Behav 2013 Jan;26(1):114-7. Epub 2012 Dec 12 doi: 10.1016/j.yebeh.2012.10.014. PMID: 23246147
Sohn YH, Lee PH
Handb Clin Neurol 2011;100:367-73. doi: 10.1016/B978-0-444-52014-2.00028-8. PMID: 21496595
Lerche H, Jurkat-Rott K, Lehmann-Horn F
Am J Med Genet 2001 Summer;106(2):146-59. doi: 10.1002/ajmg.1582. PMID: 11579435

Diagnosis

Conti V, Aracri P, Chiti L, Brusco S, Mari F, Marini C, Albanese M, Marchi A, Liguori C, Placidi F, Romigi A, Becchetti A, Guerrini R
Neurology 2015 Apr 14;84(15):1520-8. Epub 2015 Mar 13 doi: 10.1212/WNL.0000000000001471. PMID: 25770198Free PMC Article
Lu Y, Wang X
Neurol Res 2009 Mar;31(2):135-43. doi: 10.1179/174313209X393942. PMID: 19298753
Kaneko S, Okada M, Iwasa H, Yamakawa K, Hirose S
Neurosci Res 2002 Sep;44(1):11-30. doi: 10.1016/s0168-0102(02)00065-2. PMID: 12204289
Sáenz A, Galán J, Caloustian C, Lorenzo F, Márquez C, Rodríguez N, Jiménez MD, Poza JJ, Cobo AM, Grid D, Prud'homme JF, López de Munain A
Arch Neurol 1999 Aug;56(8):1004-9. doi: 10.1001/archneur.56.8.1004. PMID: 10448807
Berkovic SF, Scheffer IE
Brain Dev 1997 Jan;19(1):13-8. doi: 10.1016/s0387-7604(96)00060-5. PMID: 9071484

Therapy

Mullen SA, Carney PW, Roten A, Ching M, Lightfoot PA, Churilov L, Nair U, Li M, Berkovic SF, Petrou S, Scheffer IE
Neurology 2018 Jan 2;90(1):e67-e72. Epub 2017 Dec 1 doi: 10.1212/WNL.0000000000004769. PMID: 29196578
Delgado-Escueta AV, Bourgeois BF
Epilepsia 2008 Dec;49 Suppl 9:13-24. doi: 10.1111/j.1528-1167.2008.01922.x. PMID: 19087113
Hoda JC, Gu W, Friedli M, Phillips HA, Bertrand S, Antonarakis SE, Goudie D, Roberts R, Scheffer IE, Marini C, Patel J, Berkovic SF, Mulley JC, Steinlein OK, Bertrand D
Mol Pharmacol 2008 Aug;74(2):379-91. Epub 2008 May 2 doi: 10.1124/mol.107.044545. PMID: 18456869
Steinlein OK
Curr Drug Targets CNS Neurol Disord 2002 Aug;1(4):443-8. doi: 10.2174/1568007023339193. PMID: 12769616
Zucconi M, Oldani A, Smirne S, Ferini-Strambi L
J Clin Neurophysiol 2000 Jan;17(1):77-86. doi: 10.1097/00004691-200001000-00008. PMID: 10709813

Prognosis

Datta AN, Michoulas A, Guella I; EPGEN Study, Demos M
J Child Neurol 2019 Oct;34(12):728-734. Epub 2019 Jun 17 doi: 10.1177/0883073819854853. PMID: 31208268
Sone D, Sugawara T, Sakakibara E, Tomioka Y, Taniguchi G, Murata Y, Watanabe M, Kaneko S
Epilepsy Behav 2012 Oct;25(2):192-5. Epub 2012 Sep 29 doi: 10.1016/j.yebeh.2012.07.027. PMID: 23032131
Delgado-Escueta AV, Bourgeois BF
Epilepsia 2008 Dec;49 Suppl 9:13-24. doi: 10.1111/j.1528-1167.2008.01922.x. PMID: 19087113
Ortells MO, Barrantes GE
Br J Pharmacol 2002 Jul;136(6):883-95. doi: 10.1038/sj.bjp.0704786. PMID: 12110613Free PMC Article
Nakken KO, Magnusson A, Steinlein OK
Epilepsia 1999 Jan;40(1):88-92. doi: 10.1111/j.1528-1157.1999.tb01993.x. PMID: 9924907

Clinical prediction guides

Delgado-Escueta AV, Bourgeois BF
Epilepsia 2008 Dec;49 Suppl 9:13-24. doi: 10.1111/j.1528-1167.2008.01922.x. PMID: 19087113
Fedi M, Berkovic SF, Scheffer IE, O'Keefe G, Marini C, Mulligan R, Gong S, Tochon-Danguy H, Reutens DC
Neurology 2008 Sep 9;71(11):795-8. Epub 2008 Aug 6 doi: 10.1212/01.wnl.0000316192.52731.77. PMID: 18685138
Hoda JC, Gu W, Friedli M, Phillips HA, Bertrand S, Antonarakis SE, Goudie D, Roberts R, Scheffer IE, Marini C, Patel J, Berkovic SF, Mulley JC, Steinlein OK, Bertrand D
Mol Pharmacol 2008 Aug;74(2):379-91. Epub 2008 May 2 doi: 10.1124/mol.107.044545. PMID: 18456869
Ito M, Kobayashi K, Fujii T, Okuno T, Hirose S, Iwata H, Mitsudome A, Kaneko S
Epilepsia 2000 Jan;41(1):52-8. doi: 10.1111/j.1528-1157.2000.tb01505.x. PMID: 10643924
Sáenz A, Galán J, Caloustian C, Lorenzo F, Márquez C, Rodríguez N, Jiménez MD, Poza JJ, Cobo AM, Grid D, Prud'homme JF, López de Munain A
Arch Neurol 1999 Aug;56(8):1004-9. doi: 10.1001/archneur.56.8.1004. PMID: 10448807

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