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MedGen UID:
Concept ID:
Sign or Symptom
Synonyms: Insomnia Disorder; Insomnia Disorders; Insomnias; Sleeplessness
SNOMED CT: Sleeplessness (193462001); Insomnia (193462001)
HPO: HP:0100785
Monarch Initiative: MONDO:0013600


Persistent difficulty initiating or maintaining sleep. [from HPO]

Conditions with this feature

Wilson disease
MedGen UID:
Concept ID:
Disease or Syndrome
Wilson disease is a disorder of copper metabolism that can present with hepatic, neurologic, or psychiatric disturbances, or a combination of these, in individuals ranging from age three years to older than 50 years; symptoms vary among and within families. Liver disease includes recurrent jaundice, simple acute self-limited hepatitis-like illness, autoimmune-type hepatitis, fulminant hepatic failure, or chronic liver disease. Neurologic presentations include movement disorders (tremors, poor coordination, loss of fine-motor control, chorea, choreoathetosis) or rigid dystonia (mask-like facies, rigidity, gait disturbance, pseudobulbar involvement). Psychiatric disturbance includes depression, neurotic behaviors, disorganization of personality, and, occasionally, intellectual deterioration. Kayser-Fleischer rings, frequently present, result from copper deposition in Descemet's membrane of the cornea and reflect a high degree of copper storage in the body.
Hereditary coproporphyria
MedGen UID:
Concept ID:
Disease or Syndrome
Hereditary coproporphyria (HCP) is an acute (hepatic) porphyria in which the acute symptoms are neurovisceral and occur in discrete episodes. Attacks typically start in the abdomen with low-grade pain that slowly increases over a period of days (not hours) with nausea progressing to vomiting. In some individuals, the pain is predominantly in the back or extremities. When an acute attack is untreated, a motor neuropathy may develop over a period of days or a few weeks. The neuropathy first appears as weakness proximally in the arms and legs, then progresses distally to involve the hands and feet. Some individuals experience respiratory insufficiency due to loss of innervation of the diaphragm and muscles of respiration. Acute attacks are associated commonly with use of certain medications, caloric deprivation, and changes in female reproductive hormones. About 20% of those with an acute attack also experience photosensitivity associated with bullae and skin fragility.
Fatal familial insomnia
MedGen UID:
Concept ID:
Disease or Syndrome
Genetic prion disease generally manifests with cognitive difficulties, ataxia, and myoclonus (abrupt jerking movements of muscle groups and/or entire limbs). The order of appearance and/or predominance of these features and other associated neurologic and psychiatric findings vary. The three major phenotypes of genetic prion disease are genetic Creutzfeldt-Jakob disease (gCJD), fatal familial insomnia (FFI), and Gerstmann-Sträussler-Scheinker (GSS) syndrome. Although these phenotypes display overlapping clinical and pathologic features, recognition of these phenotypes can be useful when providing affected individuals and their families with information about the expected clinical course. The age at onset typically ranges from 50 to 60 years. The disease course ranges from a few months in gCJD and FFI to a few (up to 4, and in rare cases up to 10) years in GSS syndrome.
Progeroid short stature with pigmented nevi
MedGen UID:
Concept ID:
Disease or Syndrome
Mulvihill-Smith syndrome is characterized by premature aging, multiple pigmented nevi, lack of facial subcutaneous fat, microcephaly, short stature, sensorineural hearing loss, and mental retardation. Immunodeficiency may also be a feature. Adult manifestations include the development of tumors, a sleep disorder with severe insomnia, and cognitive decline (summary by Yagihashi et al., 2009).
Perry syndrome
MedGen UID:
Concept ID:
Disease or Syndrome
The spectrum of DCTN1-related neurodegeneration includes Perry syndrome, distal hereditary motor neuronopathy type 7B (dHMN7B), frontotemporal dementia (FTD), motor neuron disease / amyotrophic lateral sclerosis (ALS), and progressive supranuclear palsy. Some individuals present with overlapping phenotypes (e.g., FTD-ALS, Perry syndrome-dHMN7B). Perry syndrome (the most common of the phenotypes associated with DCTN1) is characterized by parkinsonism, neuropsychiatric symptoms, hypoventilation, and weight loss. The mean age of onset in those with Perry syndrome is 49 years (range: 35-70 years), and the mean disease duration is five years (range: 2-14 years). In most affected persons, the reported cause/circumstance of death relates to sudden death/hypoventilation or suicide.
Restless legs syndrome, susceptibility to, 1
MedGen UID:
Concept ID:
Restless legs syndrome (RLS) is a neurologic sleep/wake disorder characterized by uncomfortable and unpleasant sensations in the legs that appear at rest, usually at night, inducing an irresistible desire to move the legs. The disorder results in nocturnal insomnia and chronic sleep deprivation (Bonati et al., 2003). Genetic Heterogeneity of Restless Legs Syndrome RLS1 has been mapped to chromosome 12q. Other susceptibility loci for RLS include RLS2 (608831) on chromosome 14q13-q31; RLS3 (610438) on chromosome 9p24-p22; RLS4 (610439) on chromosome 2q33; RLS5 (611242) on chromosome 20p13; RLS6 (611185) on chromosome 6p21; RLS7 (612853) on chromosome 2p14; and RLS8 (615197) on chromosome 5q31.
Autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome
MedGen UID:
Concept ID:
Disease or Syndrome
Arboleda-Tham syndrome (ARTHS) is an autosomal dominant disorder with the core features of impaired intellectual development, speech delay, microcephaly, cardiac anomalies, and gastrointestinal complications (summary by Kennedy et al., 2019).
Spinocerebellar ataxia 48
MedGen UID:
Concept ID:
Disease or Syndrome
SCA48 is an autosomal dominant neurodegenerative disorder characterized by onset of gait ataxia and/or cognitive-affective symptoms in midadulthood. Patients may present with involvement of either system, but most eventually develop impairment in both. Features include gait ataxia, dysarthria, and dysphagia, as well as cognitive decline, deficits in executive function, and psychiatric or affective manifestations, such as depression, anxiety, and apathy. Additional more variable features may include movement abnormalities, such as parkinsonism, tremor, chorea, dystonia, and dysmetria; spasticity is not observed. Brain imaging shows selective atrophy of the posterior areas of the cerebellar vermis, often with bilateral T2-weighted hyperintensities in the dentate nuclei (the 'crab sign'), and diffusion tensor imaging (DTI) may show paucity of cerebellar connections to the brainstem and cerebrum. The presentation is consistent with a clinical diagnosis of cerebellar cognitive-affective syndrome (CCAS). The phenotype shows both inter- and intrafamilial variability as well as some clinical overlap with SCAR16, suggesting that mutations in the STUB1 gene result in a spectrum of neurodegenerative manifestations (summary by Genis et al., 2018; Cocozza et al., 2020; Palvadeau et al., 2020; Ravel et al., 2021). Magri et al. (2022) found evidence that heterozygous STUB1 variants alone do not cause disease but require a concurrent expanded repeat allele of the TBP gene (600075) for disease manifestation; see MOLECULAR GENETICS.
Congenital disorder of glycosylation, type iit
MedGen UID:
Concept ID:
Disease or Syndrome
Congenital disorder of glycosylation type IIt (CDG2t) is an autosomal recessive multisystemic metabolic disorder characterized by global developmental delay, poor overall growth, severely impaired intellectual development with absent language, and behavioral abnormalities. Most patients develop early-onset seizures; brain imaging tends to show white matter abnormalities. Variable dysmorphic features, including long face, almond-shaped eyes, protruding maxilla, and short philtrum, are also present. The disorder, which is associated with low levels of HDL cholesterol, results from defective posttranslational O-linked glycosylation of certain plasma lipids and proteins (summary by Zilmer et al., 2020). For an overview of congenital disorders of glycosylation, see CDG1A (212065) and CDG2A (212066).
Intellectual developmental disorder with paroxysmal dyskinesia or seizures
MedGen UID:
Concept ID:
Disease or Syndrome
Intellectual developmental disorder with paroxysmal dyskinesia or seizures (IDDPADS) is an autosomal recessive complex neurologic disorder characterized by global developmental delay with impaired intellectual development and language delay. In addition, most patients develop a paroxysmal hyperkinetic movement disorder in the first months or years of life manifest as sudden falls or backward propulsion, eye or head deviation, and dystonic limb posturing followed by chorea and dyskinetic movements. The episodes are pharmacoresistant to anticonvulsant medication. EEG may show interictal abnormalities, but are usually not consistent with epilepsy. However, some patients may also develop epileptic seizures or only have seizures without a movement disorder (summary by Doummar et al., 2020).

Professional guidelines


de Zambotti M, Goldstone A, Colrain IM, Baker FC
Sleep Med Rev 2018 Jun;39:12-24. Epub 2017 Jul 1 doi: 10.1016/j.smrv.2017.06.009. PMID: 28974427Free PMC Article
Riemann D, Baglioni C, Bassetti C, Bjorvatn B, Dolenc Groselj L, Ellis JG, Espie CA, Garcia-Borreguero D, Gjerstad M, Gonçalves M, Hertenstein E, Jansson-Fröjmark M, Jennum PJ, Leger D, Nissen C, Parrino L, Paunio T, Pevernagie D, Verbraecken J, Weeß HG, Wichniak A, Zavalko I, Arnardottir ES, Deleanu OC, Strazisar B, Zoetmulder M, Spiegelhalder K
J Sleep Res 2017 Dec;26(6):675-700. Epub 2017 Sep 5 doi: 10.1111/jsr.12594. PMID: 28875581
Santoro N, Epperson CN, Mathews SB
Endocrinol Metab Clin North Am 2015 Sep;44(3):497-515. doi: 10.1016/j.ecl.2015.05.001. PMID: 26316239Free PMC Article

Recent clinical studies


Morin CM, Jarrin DC
Sleep Med Clin 2022 Jun;17(2):173-191. Epub 2022 Apr 23 doi: 10.1016/j.jsmc.2022.03.003. PMID: 35659072
Sutton EL
Ann Intern Med 2021 Mar;174(3):ITC33-ITC48. Epub 2021 Mar 9 doi: 10.7326/AITC202103160. PMID: 33683929
Van Someren EJW
Physiol Rev 2021 Jul 1;101(3):995-1046. Epub 2020 Aug 13 doi: 10.1152/physrev.00046.2019. PMID: 32790576
Patel D, Steinberg J, Patel P
J Clin Sleep Med 2018 Jun 15;14(6):1017-1024. doi: 10.5664/jcsm.7172. PMID: 29852897Free PMC Article
de Zambotti M, Goldstone A, Colrain IM, Baker FC
Sleep Med Rev 2018 Jun;39:12-24. Epub 2017 Jul 1 doi: 10.1016/j.smrv.2017.06.009. PMID: 28974427Free PMC Article


Sutton EL
Ann Intern Med 2021 Mar;174(3):ITC33-ITC48. Epub 2021 Mar 9 doi: 10.7326/AITC202103160. PMID: 33683929
Perez MN, Salas RME
Continuum (Minneap Minn) 2020 Aug;26(4):1003-1015. doi: 10.1212/CON.0000000000000879. PMID: 32756233
Dopheide JA
Am J Manag Care 2020 Mar;26(4 Suppl):S76-S84. doi: 10.37765/ajmc.2020.42769. PMID: 32282177
Patel D, Steinberg J, Patel P
J Clin Sleep Med 2018 Jun 15;14(6):1017-1024. doi: 10.5664/jcsm.7172. PMID: 29852897Free PMC Article
de Zambotti M, Goldstone A, Colrain IM, Baker FC
Sleep Med Rev 2018 Jun;39:12-24. Epub 2017 Jul 1 doi: 10.1016/j.smrv.2017.06.009. PMID: 28974427Free PMC Article


Scott AJ, Webb TL, Martyn-St James M, Rowse G, Weich S
Sleep Med Rev 2021 Dec;60:101556. Epub 2021 Sep 23 doi: 10.1016/j.smrv.2021.101556. PMID: 34607184Free PMC Article
Freeman D, Sheaves B, Waite F, Harvey AG, Harrison PJ
Lancet Psychiatry 2020 Jul;7(7):628-637. doi: 10.1016/S2215-0366(20)30136-X. PMID: 32563308
Tang D, Li H, Chen L
Adv Exp Med Biol 2019;1130:109-128. doi: 10.1007/978-981-13-6123-4_7. PMID: 30915704
Schroeck JL, Ford J, Conway EL, Kurtzhalts KE, Gee ME, Vollmer KA, Mergenhagen KA
Clin Ther 2016 Nov;38(11):2340-2372. Epub 2016 Oct 15 doi: 10.1016/j.clinthera.2016.09.010. PMID: 27751669
Cheuk DK, Yeung WF, Chung KF, Wong V
Cochrane Database Syst Rev 2012 Sep 12;(9):CD005472. doi: 10.1002/14651858.CD005472.pub3. PMID: 22972087


Fan M, Sun D, Zhou T, Heianza Y, Lv J, Li L, Qi L
Eur Heart J 2020 Mar 14;41(11):1182-1189. doi: 10.1093/eurheartj/ehz849. PMID: 31848595Free PMC Article
Baylan S, Griffiths S, Grant N, Broomfield NM, Evans JJ, Gardani M
Sleep Med Rev 2020 Feb;49:101222. Epub 2019 Oct 28 doi: 10.1016/j.smrv.2019.101222. PMID: 31739180
Pengo MF, Won CH, Bourjeily G
Chest 2018 Jul;154(1):196-206. Epub 2018 Apr 19 doi: 10.1016/j.chest.2018.04.005. PMID: 29679598Free PMC Article
Yin X, Gou M, Xu J, Dong B, Yin P, Masquelin F, Wu J, Lao L, Xu S
Sleep Med 2017 Sep;37:193-200. Epub 2017 Mar 8 doi: 10.1016/j.sleep.2017.02.012. PMID: 28899535
O'Keefe JH, Bhatti SK, Patil HR, DiNicolantonio JJ, Lucan SC, Lavie CJ
J Am Coll Cardiol 2013 Sep 17;62(12):1043-1051. Epub 2013 Jul 17 doi: 10.1016/j.jacc.2013.06.035. PMID: 23871889

Clinical prediction guides

He D, Meng P, Li C, Jia Y, Wen Y, Pan C, Zhang Z, Zhang J, Zhang H, Chen Y, Zhao Y, Qin X, Cai Q, Wei W, Shi S, Chu X, Zhang N, Zhang F
Sleep Med 2022 Dec;100:304-310. Epub 2022 Sep 14 doi: 10.1016/j.sleep.2022.09.002. PMID: 36182724
Hao S, Tan S, Li J, Li W, Li J, Liu Y, Hong Z
Asia Pac J Clin Nutr 2022;31(3):362-370. doi: 10.6133/apjcn.202209_31(3).0004. PMID: 36173208
Yin X, Li W, Liang T, Lu B, Yue H, Li S, Zhong VW, Zhang W, Li X, Zhou S, Mi Y, Wu H, Xu S
JAMA Netw Open 2022 Jul 1;5(7):e2220563. doi: 10.1001/jamanetworkopen.2022.20563. PMID: 35797047Free PMC Article
Sumsuzzman DM, Choi J, Jin Y, Hong Y
Neurosci Biobehav Rev 2021 Aug;127:459-473. Epub 2021 May 3 doi: 10.1016/j.neubiorev.2021.04.034. PMID: 33957167
Morin CM, Belleville G, Bélanger L, Ivers H
Sleep 2011 May 1;34(5):601-8. doi: 10.1093/sleep/34.5.601. PMID: 21532953Free PMC Article

Recent systematic reviews

De Crescenzo F, D'Alò GL, Ostinelli EG, Ciabattini M, Di Franco V, Watanabe N, Kurtulmus A, Tomlinson A, Mitrova Z, Foti F, Del Giovane C, Quested DJ, Cowen PJ, Barbui C, Amato L, Efthimiou O, Cipriani A
Lancet 2022 Jul 16;400(10347):170-184. doi: 10.1016/S0140-6736(22)00878-9. PMID: 35843245
Pappa S, Ntella V, Giannakas T, Giannakoulis VG, Papoutsi E, Katsaounou P
Brain Behav Immun 2020 Aug;88:901-907. Epub 2020 May 8 doi: 10.1016/j.bbi.2020.05.026. PMID: 32437915Free PMC Article
Clark I, Landolt HP
Sleep Med Rev 2017 Feb;31:70-78. Epub 2016 Jan 30 doi: 10.1016/j.smrv.2016.01.006. PMID: 26899133
Liu L, Liu C, Wang Y, Wang P, Li Y, Li B
Curr Neuropharmacol 2015;13(4):481-93. doi: 10.2174/1570159x1304150831122734. PMID: 26412068Free PMC Article
Buysse DJ
JAMA 2013 Feb 20;309(7):706-16. doi: 10.1001/jama.2013.193. PMID: 23423416Free PMC Article

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