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Narcolepsy 7(NRCLP7)

MedGen UID:
481896
Concept ID:
C3280266
Disease or Syndrome
Synonym: NRCLP7
 
Gene (location): MOG (6p22.1)
 
Monarch Initiative: MONDO:0013652
OMIM®: 614250

Definition

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. [from MedlinePlus Genetics]

Clinical features

From HPO
Obesity
MedGen UID:
18127
Concept ID:
C0028754
Disease or Syndrome
Accumulation of substantial excess body fat.
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.
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.
Obstructive sleep apnea syndrome
MedGen UID:
101045
Concept ID:
C0520679
Disease or Syndrome
Obstructive sleep apnea is a common, chronic, complex disease associated with serious cardiovascular and neuropsychologic sequelae and with substantial social and economic costs (Palmer et al., 2003).
Excessive daytime somnolence
MedGen UID:
1635612
Concept ID:
C4551761
Sign or Symptom
A state of abnormally strong desire for sleep during the daytime.
Type II diabetes mellitus
MedGen UID:
41523
Concept ID:
C0011860
Disease or Syndrome
Type 2 diabetes mellitus is distinct from maturity-onset diabetes of the young (see 606391) in that it is polygenic, characterized by gene-gene and gene-environment interactions with onset in adulthood, usually at age 40 to 60 but occasionally in adolescence if a person is obese. The pedigrees are rarely multigenerational. The penetrance is variable, possibly 10 to 40% (Fajans et al., 2001). Persons with type 2 diabetes usually have an obese body habitus and manifestations of the so-called metabolic syndrome (see 605552), which is characterized by diabetes, insulin resistance, hypertension, and hypertriglyceridemia. Genetic Heterogeneity of Susceptibility to Type 2 Diabetes Susceptibility to T2D1 (601283) is conferred by variation in the calpain-10 gene (CAPN10; 605286) on chromosome 2q37. The T2D2 locus (601407) on chromosome 12q was found in a Finnish population. The T2D3 locus (603694) maps to chromosome 20. The T2D4 locus (608036) maps to chromosome 5q34-q35. Susceptibility to T2D5 (616087) is conferred by variation in the TBC1D4 gene (612465) on chromosome 13q22. A mutation has been observed in hepatocyte nuclear factor-4-alpha (HNF4A; 600281.0004) in a French family with NIDDM of late onset. Mutations in the NEUROD1 gene (601724) on chromosome 2q32 were found to cause type 2 diabetes mellitus in 2 families. Mutation in the GLUT2 glucose transporter was associated with NIDDM in 1 patient (138160.0001). Mutation in the MAPK8IP1 gene, which encodes the islet-brain-1 protein, was found in a family with type 2 diabetes in individuals in 4 successive generations (604641.0001). Polymorphism in the KCNJ11 gene (600937.0014) confers susceptibility. In French white families, Vionnet et al. (2000) found evidence for a susceptibility locus for type 2 diabetes on 3q27-qter. They confirmed the diabetes susceptibility locus on 1q21-q24 reported by Elbein et al. (1999) in whites and by Hanson et al. (1998) in Pima Indians. A mutation in the GPD2 gene (138430.0001) on chromosome 2q24.1, encoding mitochondrial glycerophosphate dehydrogenase, was found in a patient with type 2 diabetes mellitus and in his glucose-intolerant half sister. Mutations in the PAX4 gene (167413) have been identified in patients with type 2 diabetes. Triggs-Raine et al. (2002) stated that in the Oji-Cree, a gly319-to-ser change in HNF1-alpha (142410.0008) behaves as a susceptibility allele for type 2 diabetes. Mutation in the HNF1B gene (189907.0007) was found in 2 Japanese patients with typical late-onset type 2 diabetes. Mutations in the IRS1 gene (147545) have been found in patients with type 2 diabetes. A missense mutation in the AKT2 gene (164731.0001) caused autosomal dominant type 2 diabetes in 1 family. A (single-nucleotide polymorphism) SNP in the 3-prime untranslated region of the resistin gene (605565.0001) was associated with susceptibility to diabetes and to insulin resistance-related hypertension in Chinese subjects. Susceptibility to insulin resistance has been associated with polymorphism in the TCF1 (142410.0011), PPP1R3A (600917.0001), PTPN1 (176885.0001), ENPP1 (173335.0006), IRS1 (147545.0002), and EPHX2 (132811.0001) genes. The K121Q polymorphism of ENPP1 (173335.0006) is associated with susceptibility to type 2 diabetes; a haplotype defined by 3 SNPs of this gene, including K121Q, is associated with obesity, glucose intolerance, and type 2 diabetes. A SNP in the promoter region of the hepatic lipase gene (151670.0004) predicts conversion from impaired glucose tolerance to type 2 diabetes. Variants of transcription factor 7-like-2 (TCF7L2; 602228.0001), located on 10q, have also been found to confer risk of type 2 diabetes. A common sequence variant, rs10811661, on chromosome 9p21 near the CDKN2A (600160) and CDKN2B (600431) genes has been associated with risk of type 2 diabetes. Variation in the PPARG gene (601487) has been associated with risk of type 2 diabetes. A promoter polymorphism in the IL6 gene (147620) is associated with susceptibility to NIDDM. Variation in the KCNJ15 gene (602106) has been associated with T2DM in lean Asians. Variation in the SLC30A8 gene (611145) has been associated with susceptibility to T2D. Variation in the HMGA1 gene (600701.0001) is associated with an increased risk of type 2 diabetes. Mutation in the MTNR1B gene (600804) is associated with susceptibility to type 2 diabetes. Protection Against Type 2 Diabetes Mellitus Protein-truncating variants in the SLC30A8 (611145) have been associated with a reduced risk for T2D.

Professional guidelines

PubMed

Cuomo MC, Sheehan AH, Jordan JK
J Pharm Pract 2022 Dec;35(6):963-970. Epub 2021 Apr 22 doi: 10.1177/08971900211009080. PMID: 33882756

Recent clinical studies

Etiology

Ollila HM, Sharon E, Lin L, Sinnott-Armstrong N, Ambati A, Yogeshwar SM, Hillary RP, Jolanki O, Faraco J, Einen M, Luo G, Zhang J, Han F, Yan H, Dong XS, Li J, Zhang J, Hong SC, Kim TW, Dauvilliers Y, Barateau L, Lammers GJ, Fronczek R, Mayer G, Santamaria J, Arnulf I, Knudsen-Heier S, Bredahl MKL, Thorsby PM, Plazzi G, Pizza F, Moresco M, Crowe C, Van den Eeden SK, Lecendreux M, Bourgin P, Kanbayashi T, Martínez-Orozco FJ, Peraita-Adrados R, Benetó A, Montplaisir J, Desautels A, Huang YS; FinnGen, Jennum P, Nevsimalova S, Kemlink D, Iranzo A, Overeem S, Wierzbicka A, Geisler P, Sonka K, Honda M, Högl B, Stefani A, Coelho FM, Mantovani V, Feketeova E, Wadelius M, Eriksson N, Smedje H, Hallberg P, Hesla PE, Rye D, Pelin Z, Ferini-Strambi L, Bassetti CL, Mathis J, Khatami R, Aran A, Nampoothiri S, Olsson T, Kockum I, Partinen M, Perola M, Kornum BR, Rueger S, Winkelmann J, Miyagawa T, Toyoda H, Khor SS, Shimada M, Tokunaga K, Rivas M, Pritchard JK, Risch N, Kutalik Z, O'Hara R, Hallmayer J, Ye CJ, Mignot EJ
Nat Commun 2023 May 15;14(1):2709. doi: 10.1038/s41467-023-36120-z. PMID: 37188663Free PMC Article
Dauvilliers Y, Lecendreux M, Lammers GJ, Franco P, Poluektov M, Caussé C, Lecomte I, Lecomte JM, Lehert P, Schwartz JC, Plazzi G
Lancet Neurol 2023 Apr;22(4):303-311. doi: 10.1016/S1474-4422(23)00036-4. PMID: 36931805
Reynolds AM, Spaeth AM, Hale L, Williamson AA, LeBourgeois MK, Wong SD, Hartstein LE, Levenson JC, Kwon M, Hart CN, Greer A, Richardson CE, Gradisar M, Clementi MA, Simon SL, Reuter-Yuill LM, Picchietti DL, Wild S, Tarokh L, Sexton-Radek K, Malow BA, Lenker KP, Calhoun SL, Johnson DA, Lewin D, Carskadon MA
Sleep 2023 Jul 11;46(7) doi: 10.1093/sleep/zsad060. PMID: 36881684Free PMC Article
Howell M, Avidan AY, Foldvary-Schaefer N, Malkani RG, During EH, Roland JP, McCarter SJ, Zak RS, Carandang G, Kazmi U, Ramar K
J Clin Sleep Med 2023 Apr 1;19(4):759-768. doi: 10.5664/jcsm.10424. PMID: 36515157Free PMC Article
Buonocore SM, van der Most RG
Front Immunol 2022;13:902840. Epub 2022 Oct 12 doi: 10.3389/fimmu.2022.902840. PMID: 36311717Free PMC Article

Diagnosis

Arnulf I, Dodet P, Leu-Semenescu S, Maranci JB
Rev Neurol (Paris) 2023 Oct;179(7):741-754. Epub 2023 Sep 6 doi: 10.1016/j.neurol.2023.08.010. PMID: 37684104
Barateau L, Pizza F, Chenini S, Peter-Derex L, Dauvilliers Y
Rev Neurol (Paris) 2023 Oct;179(7):727-740. Epub 2023 Aug 25 doi: 10.1016/j.neurol.2023.08.001. PMID: 37634997
Shelton AR
Continuum (Minneap Minn) 2023 Aug 1;29(4):1205-1233. doi: 10.1212/CON.0000000000001285. PMID: 37590830
Reading PJ
J Neurol 2019 Jul;266(7):1809-1815. Epub 2019 Apr 19 doi: 10.1007/s00415-019-09310-3. PMID: 31004212
Depner CM, Stothard ER, Wright KP Jr
Curr Diab Rep 2014 Jul;14(7):507. doi: 10.1007/s11892-014-0507-z. PMID: 24816752Free PMC Article

Therapy

Ollila HM, Sharon E, Lin L, Sinnott-Armstrong N, Ambati A, Yogeshwar SM, Hillary RP, Jolanki O, Faraco J, Einen M, Luo G, Zhang J, Han F, Yan H, Dong XS, Li J, Zhang J, Hong SC, Kim TW, Dauvilliers Y, Barateau L, Lammers GJ, Fronczek R, Mayer G, Santamaria J, Arnulf I, Knudsen-Heier S, Bredahl MKL, Thorsby PM, Plazzi G, Pizza F, Moresco M, Crowe C, Van den Eeden SK, Lecendreux M, Bourgin P, Kanbayashi T, Martínez-Orozco FJ, Peraita-Adrados R, Benetó A, Montplaisir J, Desautels A, Huang YS; FinnGen, Jennum P, Nevsimalova S, Kemlink D, Iranzo A, Overeem S, Wierzbicka A, Geisler P, Sonka K, Honda M, Högl B, Stefani A, Coelho FM, Mantovani V, Feketeova E, Wadelius M, Eriksson N, Smedje H, Hallberg P, Hesla PE, Rye D, Pelin Z, Ferini-Strambi L, Bassetti CL, Mathis J, Khatami R, Aran A, Nampoothiri S, Olsson T, Kockum I, Partinen M, Perola M, Kornum BR, Rueger S, Winkelmann J, Miyagawa T, Toyoda H, Khor SS, Shimada M, Tokunaga K, Rivas M, Pritchard JK, Risch N, Kutalik Z, O'Hara R, Hallmayer J, Ye CJ, Mignot EJ
Nat Commun 2023 May 15;14(1):2709. doi: 10.1038/s41467-023-36120-z. PMID: 37188663Free PMC Article
Howell M, Avidan AY, Foldvary-Schaefer N, Malkani RG, During EH, Roland JP, McCarter SJ, Zak RS, Carandang G, Kazmi U, Ramar K
J Clin Sleep Med 2023 Apr 1;19(4):759-768. doi: 10.5664/jcsm.10424. PMID: 36515157Free PMC Article
Kushida CA, Shapiro CM, Roth T, Thorpy MJ, Corser BC, Ajayi AO, Rosenberg R, Roy A, Seiden D, Dubow J, Dauvilliers Y
Sleep 2022 Jun 13;45(6) doi: 10.1093/sleep/zsab200. PMID: 34358324Free PMC Article
Felmlee MA, Morse BL, Morris ME
AAPS J 2021 Jan 8;23(1):22. doi: 10.1208/s12248-020-00543-z. PMID: 33417072Free PMC Article
Thorpy MJ, Shapiro C, Mayer G, Corser BC, Emsellem H, Plazzi G, Chen D, Carter LP, Wang H, Lu Y, Black J, Dauvilliers Y
Ann Neurol 2019 Mar;85(3):359-370. doi: 10.1002/ana.25423. PMID: 30694576Free PMC Article

Prognosis

Barateau L, Pizza F, Chenini S, Peter-Derex L, Dauvilliers Y
Rev Neurol (Paris) 2023 Oct;179(7):727-740. Epub 2023 Aug 25 doi: 10.1016/j.neurol.2023.08.001. PMID: 37634997
Baillieul S, Denis C, Barateau L, Arquizan C, Detante O, Pépin JL, Dauvilliers Y, Tamisier R
Rev Neurol (Paris) 2023 Oct;179(7):782-792. Epub 2023 Aug 21 doi: 10.1016/j.neurol.2023.08.004. PMID: 37612191
Howell M, Avidan AY, Foldvary-Schaefer N, Malkani RG, During EH, Roland JP, McCarter SJ, Zak RS, Carandang G, Kazmi U, Ramar K
J Clin Sleep Med 2023 Apr 1;19(4):759-768. doi: 10.5664/jcsm.10424. PMID: 36515157Free PMC Article
Maski K, Trotti LM, Kotagal S, Robert Auger R, Rowley JA, Hashmi SD, Watson NF
J Clin Sleep Med 2021 Sep 1;17(9):1881-1893. doi: 10.5664/jcsm.9328. PMID: 34743789Free PMC Article
Sarkanen TO, Alakuijala APE, Dauvilliers YA, Partinen MM
Sleep Med Rev 2018 Apr;38:177-186. Epub 2017 Jun 20 doi: 10.1016/j.smrv.2017.06.006. PMID: 28847694

Clinical prediction guides

Dauvilliers Y, Lecendreux M, Lammers GJ, Franco P, Poluektov M, Caussé C, Lecomte I, Lecomte JM, Lehert P, Schwartz JC, Plazzi G
Lancet Neurol 2023 Apr;22(4):303-311. doi: 10.1016/S1474-4422(23)00036-4. PMID: 36931805
Buonocore SM, van der Most RG
Front Immunol 2022;13:902840. Epub 2022 Oct 12 doi: 10.3389/fimmu.2022.902840. PMID: 36311717Free PMC Article
Licis A
Continuum (Minneap Minn) 2020 Aug;26(4):1034-1069. doi: 10.1212/CON.0000000000000897. PMID: 32756235
Reading PJ
J Neurol 2019 Jul;266(7):1809-1815. Epub 2019 Apr 19 doi: 10.1007/s00415-019-09310-3. PMID: 31004212
Thorpy MJ, Shapiro C, Mayer G, Corser BC, Emsellem H, Plazzi G, Chen D, Carter LP, Wang H, Lu Y, Black J, Dauvilliers Y
Ann Neurol 2019 Mar;85(3):359-370. doi: 10.1002/ana.25423. PMID: 30694576Free PMC Article

Recent systematic reviews

Hsu CW, Tseng PT, Tu YK, Lin PY, Wang LJ, Hung CF, Yang YH, Kao HY, Yeh CB, Lai HC, Chen TY
J Clin Sleep Med 2022 Apr 1;18(4):1113-1120. doi: 10.5664/jcsm.9816. PMID: 34893148Free PMC Article
Maski K, Trotti LM, Kotagal S, Robert Auger R, Rowley JA, Hashmi SD, Watson NF
J Clin Sleep Med 2021 Sep 1;17(9):1881-1893. doi: 10.5664/jcsm.9328. PMID: 34743789Free PMC Article
Mohammadi S, Moosaie F, Saghazadeh A, Mahmoudi M, Rezaei N
Sleep Med 2021 May;81:268-284. Epub 2021 Feb 24 doi: 10.1016/j.sleep.2021.02.040. PMID: 33740593
Sarkanen TO, Alakuijala APE, Dauvilliers YA, Partinen MM
Sleep Med Rev 2018 Apr;38:177-186. Epub 2017 Jun 20 doi: 10.1016/j.smrv.2017.06.006. PMID: 28847694
Alshaikh MK, Tricco AC, Tashkandi M, Mamdani M, Straus SE, BaHammam AS
J Clin Sleep Med 2012 Aug 15;8(4):451-8. doi: 10.5664/jcsm.2048. PMID: 22893778Free PMC Article

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