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Narcolepsy 1(NRCLP1)

MedGen UID:
371809
Concept ID:
C1834372
Disease or Syndrome
Synonyms: Gelineau syndrome; Gelineau's syndrome; Narcolepsy Risk Factor; Narcoleptic syndrome; NARCOLEPTIC SYNDROME 1; NRCLP1; Paroxysmal sleep
 
Gene (location): HCRT (17q21.2)
 
Monarch Initiative: MONDO:0008062
OMIM®: 161400

Definition

Adie (1926) first delineated narcolepsy as a separate and specific entity. It is a sleep disorder characterized by attacks of disabling daytime drowsiness and low alertness. The normal physiologic components of rapid eye movement (REM) sleep, dreaming and loss of muscle tone, are separated and also occur while the subject is awake, resulting in half-sleep dreams and episodes of skeletal muscle paralysis and atonia (cataplexy and sleep paralysis). Unlike normal sleep, that of narcolepsy often begins with REM activity and the time taken to fall asleep is shorter than normal. In contrast to animal models, human narcolepsy is not a simple genetic disorder. Most human cases of narcolepsy are sporadic and carry a specific HLA haplotype (Peyron et al., 2000). Familial cases are the exception rather than the rule, and monozygotic twins show only partial concordance (25 to 31%) (Mignot, 1998). Genetic Heterogeneity of Narcolepsy Additional narcolepsy loci have been mapped to chromosomes 4 (NRCLP2; 605841), 21q (NRCLP3; 609039), 22q13 (NRCLP4; 612417), 14q11 (NRCLP5; 612851), and 19p13.2 (NRCLP6; 614223). NRCLP7 (614250) is caused by mutation in the MOG gene (159465) on chromosome 6p22. Resistance to narcolepsy is associated with minor alleles of a SNP and a marker in the NLC1A gene (610259) on chromosome 21q22. [from OMIM]

Additional description

From MedlinePlus Genetics
Some people with narcolepsy have all of the major features of the disorder, while others have only one or two. Most of the signs and symptoms persist throughout life, although episodes of cataplexy may become less frequent with age and treatment.

Narcolepsy also affects nighttime sleep. Most affected individuals have trouble sleeping for more than a few hours at night. They often experience vivid hallucinations while falling asleep (hypnogogic hallucinations) or while waking up (hypnopompic hallucinations). Affected individuals often have realistic and distressing dreams, and they may act out their dreams by moving excessively or talking in their sleep. Many people with narcolepsy also experience sleep paralysis, which is an inability to move or speak for a short period while falling asleep or awakening. The combination of hallucinations, vivid dreams, and sleep paralysis is often frightening and unpleasant for affected individuals.

Another common feature of narcolepsy is cataplexy, which is a sudden loss of muscle tone in response to strong emotion (such as laughing, surprise, or anger). These episodes of muscle weakness can cause an affected person to slump over or fall, which occasionally leads to injury. Episodes of cataplexy usually last just a few seconds, and they may occur from several times a day to a few times a year. Most people diagnosed with narcolepsy also have cataplexy. However, some do not, which has led researchers to distinguish two major forms of the condition: narcolepsy with cataplexy and narcolepsy without cataplexy.

Narcolepsy is characterized by excessive daytime sleepiness. Affected individuals feel tired during the day, and several times a day they may experience an overwhelming urge to sleep. "Sleep attacks" can occur at unusual times, such as during a meal or in the middle of a conversation. They last from a few seconds to a few minutes and often lead to a longer nap, after which affected individuals wake up feeling refreshed.

Narcolepsy is a chronic sleep disorder that disrupts the normal sleep-wake cycle. Although this condition can appear at any age, it most often begins in adolescence.  https://medlineplus.gov/genetics/condition/narcolepsy

Clinical features

From HPO
Cataplexy
MedGen UID:
2862
Concept ID:
C0007384
Disease or Syndrome
A sudden and transient episode of bilateral loss of muscle tone, often triggered by emotions.
Narcolepsy
MedGen UID:
45001
Concept ID:
C0027404
Disease or Syndrome
An abnormal phenomenon characterized by a classic tetrad of excessive daytime sleepiness with irresistible sleep attacks, cataplexy (sudden bilateral loss of muscle tone), hypnagogic hallucinations, and sleep paralysis.
Hypnagogic hallucination
MedGen UID:
68578
Concept ID:
C0233773
Sign or Symptom
Hypnagogic hallucinations are brief hallucinations that occur as you are falling asleep.
Abnormal rapid eye movement sleep
MedGen UID:
488885
Concept ID:
C0392188
Finding
Abnormality of REM Sleep are phases of REM sleep are characterized by desynchronized EEG patterns, increases in heart rate and blood pressure, sympathetic activation, and a profound loss of muscle tone except for the eye and middle-ear muscles. There are also phases of rapid eye movements.
Hypnopompic hallucination
MedGen UID:
140858
Concept ID:
C0424082
Mental or Behavioral Dysfunction
Brief hallucinations that occur as you wake up in the morning, in a state that falls somewhere between dreaming and being fully awake.
Sleep paralysis
MedGen UID:
96820
Concept ID:
C0456511
Disease or Syndrome
An inability to move the body at the onset of sleep or upon awakening from sleep, lasting for seconds to a few minutes.
Paroxysmal drowsiness
MedGen UID:
871232
Concept ID:
C4025713
Disease or Syndrome
A neurological disorder marked by a sudden recurrent uncontrollable compulsion to sleep
Excessive daytime somnolence
MedGen UID:
1635612
Concept ID:
C4551761
Sign or Symptom
A state of abnormally strong desire for sleep during the daytime.

Professional guidelines

PubMed

Takenoshita S, Nishino S
Sleep Med Clin 2020 Jun;15(2):177-194. doi: 10.1016/j.jsmc.2020.02.006. PMID: 32386693
Moresco M, Pizza F, Antelmi E, Plazzi G
Curr Drug Metab 2018;19(13):1073-1079. doi: 10.2174/1389200219666180305153134. PMID: 29512449
Takenoshita S, Nishino S
Sleep Med Clin 2017 Sep;12(3):461-478. Epub 2017 Jun 7 doi: 10.1016/j.jsmc.2017.03.019. PMID: 28778242

Recent clinical studies

Etiology

Shan L, Balesar R, Swaab DF, Lammers GJ, Fronczek R
Ann Neurol 2022 Feb;91(2):282-288. Epub 2022 Jan 19 doi: 10.1002/ana.26300. PMID: 34981555Free PMC Article
Jaumally BA, Das A, Cassell NC, Pachecho GN, Majid R, Bashoura L, Balachandran DD, Faiz SA
Sleep Breath 2021 Jun;25(2):1063-1067. Epub 2020 Sep 16 doi: 10.1007/s11325-020-02151-9. PMID: 32939599
Barateau L, Lopez R, Chenini S, Pesenti C, Rassu AL, Jaussent I, Dauvilliers Y
Neurology 2020 Nov 17;95(20):e2755-e2768. Epub 2020 Sep 22 doi: 10.1212/WNL.0000000000010737. PMID: 32963102
Torstensen EW, Brinth LS, Mehlsen J, Kornum BR, Jennum PJ
Dan Med J 2018 Nov;65(11) PMID: 30382019
Kornum BR, Knudsen S, Ollila HM, Pizza F, Jennum PJ, Dauvilliers Y, Overeem S
Nat Rev Dis Primers 2017 Feb 9;3:16100. doi: 10.1038/nrdp.2016.100. PMID: 28179647

Diagnosis

Krahn LE, Zee PC, Thorpy MJ
Adv Ther 2022 Jan;39(1):221-243. Epub 2021 Dec 11 doi: 10.1007/s12325-021-01992-4. PMID: 34894325Free PMC Article
Dauvilliers Y
Front Neurol Neurosci 2021;45:139-149. Epub 2021 May 28 doi: 10.1159/000514967. PMID: 34052817
Postiglione E, Antelmi E, Pizza F, Lecendreux M, Dauvilliers Y, Plazzi G
Sleep Med Rev 2018 Apr;38:70-85. Epub 2017 May 8 doi: 10.1016/j.smrv.2017.04.003. PMID: 28666745
Schneider L, Mignot E
Semin Neurol 2017 Aug;37(4):446-460. Epub 2017 Aug 24 doi: 10.1055/s-0037-1605554. PMID: 28837992
Kornum BR, Knudsen S, Ollila HM, Pizza F, Jennum PJ, Dauvilliers Y, Overeem S
Nat Rev Dis Primers 2017 Feb 9;3:16100. doi: 10.1038/nrdp.2016.100. PMID: 28179647

Therapy

Ayoub I, Freeman SA, Saoudi A, Liblau R
J Neuroimmunol 2024 Aug 15;393:578383. Epub 2024 Jun 1 doi: 10.1016/j.jneuroim.2024.578383. PMID: 39032452
Ingravallo F, Bassi C, Zenesini C, Vignatelli L, Pagotto U, Pizza F, Plazzi G
J Sleep Res 2024 Oct;33(5):e14157. Epub 2024 Feb 6 doi: 10.1111/jsr.14157. PMID: 38318948
Torstensen EW, Brinth LS, Mehlsen J, Kornum BR, Jennum PJ
Dan Med J 2018 Nov;65(11) PMID: 30382019
Barateau L, Liblau R, Peyron C, Dauvilliers Y
CNS Drugs 2017 Oct;31(10):821-834. doi: 10.1007/s40263-017-0464-6. PMID: 28940143
Kornum BR, Knudsen S, Ollila HM, Pizza F, Jennum PJ, Dauvilliers Y, Overeem S
Nat Rev Dis Primers 2017 Feb 9;3:16100. doi: 10.1038/nrdp.2016.100. PMID: 28179647

Prognosis

Mandagere V, Rayment D
Neurocase 2023 Jun;29(3):87-89. Epub 2024 Apr 27 doi: 10.1080/13554794.2024.2347606. PMID: 38678310
Dauvilliers Y
Front Neurol Neurosci 2021;45:139-149. Epub 2021 May 28 doi: 10.1159/000514967. PMID: 34052817
Calandra-Buonaura G, Provini F, Guaraldi P, Plazzi G, Cortelli P
Sleep Med Rev 2016 Apr;26:43-56. Epub 2015 Jun 3 doi: 10.1016/j.smrv.2015.05.005. PMID: 26146026
Baiardi S, Vandi S, Pizza F, Alvisi L, Toscani L, Zambrelli E, Tinuper P, Mayer G, Plazzi G
J Clin Sleep Med 2015 Nov 15;11(11):1257-62. doi: 10.5664/jcsm.5180. PMID: 26156948Free PMC Article
Filardi M, Pizza F, Martoni M, Vandi S, Plazzi G, Natale V
Sleep Med 2015 Jan;16(1):126-30. Epub 2014 Nov 13 doi: 10.1016/j.sleep.2014.08.017. PMID: 25547035

Clinical prediction guides

Vringer M, Zhou J, Gool JK, Bijlenga D, Lammers GJ, Fronczek R, Schinkelshoek MS
Sleep Med Rev 2024 Dec;78:101993. Epub 2024 Aug 15 doi: 10.1016/j.smrv.2024.101993. PMID: 39241492
Jaumally BA, Das A, Cassell NC, Pachecho GN, Majid R, Bashoura L, Balachandran DD, Faiz SA
Sleep Breath 2021 Jun;25(2):1063-1067. Epub 2020 Sep 16 doi: 10.1007/s11325-020-02151-9. PMID: 32939599
Barateau L, Lopez R, Chenini S, Pesenti C, Rassu AL, Jaussent I, Dauvilliers Y
Neurology 2020 Nov 17;95(20):e2755-e2768. Epub 2020 Sep 22 doi: 10.1212/WNL.0000000000010737. PMID: 32963102
Ponziani V, Gennari M, Pizza F, Balsamo A, Bernardi F, Plazzi G
J Clin Sleep Med 2016 Dec 15;12(12):1649-1657. doi: 10.5664/jcsm.6352. PMID: 27707443Free PMC Article
Calandra-Buonaura G, Provini F, Guaraldi P, Plazzi G, Cortelli P
Sleep Med Rev 2016 Apr;26:43-56. Epub 2015 Jun 3 doi: 10.1016/j.smrv.2015.05.005. PMID: 26146026

Recent systematic reviews

Capittini C, De Silvestri A, Terzaghi M, Scotti V, Rebuffi C, Pasi A, Manni R, Martinetti M, Tinelli C
Sleep Med 2018 Dec;52:150-157. Epub 2018 Sep 20 doi: 10.1016/j.sleep.2018.08.024. PMID: 30321823

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