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Autosomal dominant nocturnal frontal lobe epilepsy 4(ENFL4)

MedGen UID:
332082
Concept ID:
C1835905
Disease or Syndrome
Synonyms: CHRNA2-Related Nocturnal Frontal Lobe Epilepsy, Autosomal Dominant; EPILEPSY, FAMILIAL, WITH NOCTURNAL WANDERING AND ICTAL FEAR; Epilepsy, nocturnal frontal lobe, type 4
 
Gene (location): CHRNA2 (8p21.2)
 
Monarch Initiative: MONDO:0012474
OMIM®: 610353

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
Nocturnal frontal lobe epilepsy is a childhood-onset focal epilepsy that displays clusters of sleep-related hypermotor seizures (summary by Aridon et al., 2006). Some patients with CHRNA2 mutations may have a slightly different phenotype that is more consistent with a clinical diagnosis of benign familial infantile seizures (BFIS6) (Trivisano et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of nocturnal frontal lobe epilepsy, see ENFL1 (600513). For a general phenotypic description and a discussion of genetic heterogeneity of benign familial infantile seizures, see BFIS1 (601764).  http://www.omim.org/entry/610353
From MedlinePlus Genetics
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.

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.

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.

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 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.  https://medlineplus.gov/genetics/condition/autosomal-dominant-nocturnal-frontal-lobe-epilepsy

Clinical features

From HPO
Shivering
MedGen UID:
48649
Concept ID:
C0036973
Finding
Involuntary contraction or twitching of the muscles.
Atypical behavior
MedGen UID:
14048
Concept ID:
C0004941
Sign or Symptom
Atypical behavior is an abnormality in a person's actions that can be controlled or modulated by the will of the individual. While abnormal behaviors can be difficult to control, they are distinct from other abnormal actions that cannot be affected by the individual's will.
Confusion
MedGen UID:
3587
Concept ID:
C0009676
Mental or Behavioral Dysfunction
Lack of clarity and coherence of thought, perception, understanding, or action.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Nocturnal seizures
MedGen UID:
581539
Concept ID:
C0393719
Disease or Syndrome
Seizures that occur while the affected individual is sleeping.
Neurodevelopmental abnormality
MedGen UID:
868343
Concept ID:
C4022737
Pathologic Function
A deviation from normal of the neurological development of a child, which may include any or all of the aspects of the development of personal, social, gross or fine motor, and cognitive abilities.

Recent clinical studies

Etiology

Fox J, Thodeson DM, Dolce AM
J Child Neurol 2021 Apr;36(5):371-377. Epub 2020 Dec 7 doi: 10.1177/0883073820974851. PMID: 33284031
Garibotto V, Wissmeyer M, Giavri Z, Goldstein R, Seimbille Y, Seeck M, Ratib O, Haller S, Picard F
Eur J Nucl Med Mol Imaging 2019 Feb;46(2):385-395. Epub 2018 Sep 29 doi: 10.1007/s00259-018-4175-0. PMID: 30269157
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
Sohn YH, Lee PH
Handb Clin Neurol 2011;100:367-73. doi: 10.1016/B978-0-444-52014-2.00028-8. PMID: 21496595
Wood AG, Saling MM, Fedi M, Berkovic SF, Scheffer IE, Benjamin C, Reutens DC
Epilepsy Behav 2010 Apr;17(4):531-5. Epub 2010 Feb 26 doi: 10.1016/j.yebeh.2010.01.168. PMID: 20189461

Diagnosis

Díaz-Otero F, Quesada M, Morales-Corraliza J, Martínez-Parra C, Gómez-Garre P, Serratosa JM
Epilepsia 2008 Mar;49(3):516-20. Epub 2007 Sep 26 doi: 10.1111/j.1528-1167.2007.01328.x. PMID: 17900292
Combi R, Dalprà L, Ferini-Strambi L, Tenchini ML
Ann Neurol 2005 Dec;58(6):899-904. doi: 10.1002/ana.20660. PMID: 16222669
Raggenbass M, Bertrand D
J Neurobiol 2002 Dec;53(4):580-9. doi: 10.1002/neu.10152. PMID: 12436422
Leppert MF, Singh N
Semin Neurol 1999;19(4):397-405. doi: 10.1055/s-2008-1040854. PMID: 10716662
Berkovic SF, Scheffer IE
Brain Dev 1997 Jan;19(1):13-8. doi: 10.1016/s0387-7604(96)00060-5. PMID: 9071484

Therapy

Fox J, Thodeson DM, Dolce AM
J Child Neurol 2021 Apr;36(5):371-377. Epub 2020 Dec 7 doi: 10.1177/0883073820974851. PMID: 33284031
O'Reilly C, Chapotot F, Pittau F, Mella N, Picard F
J Sleep Res 2019 Aug;28(4):e12800. Epub 2018 Dec 18 doi: 10.1111/jsr.12800. PMID: 30565327
Qu J, Zhang Y, Yang ZQ, Mao XY, Zhou BT, Yin JY, He H, Li XP, Long HY, Lv N, Xu XJ, Xiao B, Zhang Y, Tang Q, Hu DL, Zhou HH, Liu ZQ
CNS Neurosci Ther 2014 Feb;20(2):140-6. Epub 2013 Nov 27 doi: 10.1111/cns.12169. PMID: 24279416Free PMC Article
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

Prognosis

Kurahashi H, Wang JW, Ishii A, Kojima T, Wakai S, Kizawa T, Fujimoto Y, Kikkawa K, Yoshimura K, Inoue T, Yasumoto S, Ogawa A, Kaneko S, Hirose S
Neurology 2009 Oct 13;73(15):1214-7. doi: 10.1212/WNL.0b013e3181bc0158. PMID: 19822871
Ortells MO, Barrantes GE
Br J Pharmacol 2002 Jul;136(6):883-95. doi: 10.1038/sj.bjp.0704786. PMID: 12110613Free PMC Article

Clinical prediction guides

Garibotto V, Wissmeyer M, Giavri Z, Goldstein R, Seimbille Y, Seeck M, Ratib O, Haller S, Picard F
Eur J Nucl Med Mol Imaging 2019 Feb;46(2):385-395. Epub 2018 Sep 29 doi: 10.1007/s00259-018-4175-0. PMID: 30269157
Ohba C, Kato M, Takahashi N, Osaka H, Shiihara T, Tohyama J, Nabatame S, Azuma J, Fujii Y, Hara M, Tsurusawa R, Inoue T, Ogata R, Watanabe Y, Togashi N, Kodera H, Nakashima M, Tsurusaki Y, Miyake N, Tanaka F, Saitsu H, Matsumoto N
Epilepsia 2015 Sep;56(9):e121-8. Epub 2015 Jul 3 doi: 10.1111/epi.13072. PMID: 26140313
Picard F, Baulac S, Kahane P, Hirsch E, Sebastianelli R, Thomas P, Vigevano F, Genton P, Guerrini R, Gericke CA, An I, Rudolf G, Herman A, Brice A, Marescaux C, LeGuern E
Brain 2000 Jun;123 ( Pt 6):1247-62. doi: 10.1093/brain/123.6.1247. PMID: 10825362
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
Phillips HA, Scheffer IE, Crossland KM, Bhatia KP, Fish DR, Marsden CD, Howell SJ, Stephenson JB, Tolmie J, Plazzi G, Eeg-Olofsson O, Singh R, Lopes-Cendes I, Andermann E, Andermann F, Berkovic SF, Mulley JC
Am J Hum Genet 1998 Oct;63(4):1108-16. doi: 10.1086/302047. PMID: 9758605Free PMC Article

Recent systematic reviews

Fox J, Thodeson DM, Dolce AM
J Child Neurol 2021 Apr;36(5):371-377. Epub 2020 Dec 7 doi: 10.1177/0883073820974851. PMID: 33284031

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