Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Apr 5;86(14):1336-1343.
doi: 10.1212/WNL.0000000000002542. Epub 2016 Mar 4.

Restless legs syndrome associated with major diseases: A systematic review and new concept

Claudia Trenkwalder  1 , Richard Allen  2 , Birgit Högl  2 , Walter Paulus  2 , Juliane Winkelmann  1
Affiliations
Review

Restless legs syndrome associated with major diseases: A systematic review and new concept

Claudia Trenkwalder et al. Neurology. .

Abstract

Recent publications on both the genetics and environmental factors of restless legs syndrome (RLS) defined as a clinical disorder suggest that overlapping genetic risk factors may play a role in primary (idiopathic) and secondary (symptomatic) RLS. Following a systematic literature search of RLS associated with comorbidities, we identified an increased prevalence of RLS only in iron deficiency and kidney disease. In cardiovascular disease, arterial hypertension, diabetes, migraine, and Parkinson disease, the methodology of studies was poor, but an association might be possible. There is insufficient evidence for conditions such as anemia (without iron deficiency), chronic obstructive pulmonary disease, multiple sclerosis, headache, stroke, narcolepsy, and ataxias. Based on possible gene-microenvironmental interaction, the classifications primary and secondary RLS may suggest an inappropriate causal relation. We recognize that in some conditions, treatment of the underlying disease should be achieved as far as possible to reduce or eliminate RLS symptoms. RLS might be seen as a continuous spectrum with a major genetic contribution at one end and a major environmental or comorbid disease contribution at the other.

PubMed Disclaimer

Figures

Figure
Figure. Model of the hypothesis that the more genetic factors contribute to the manifestation of restless legs syndrome (RLS), the less environmental trigger is needed
CVD = cardiovascular disease; PD = Parkinson disease.
See this image and copyright information in PMC

Comment in

Similar articles

See all similar articles

Cited by

  • Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction.
    Schormair B, Zhao C, Bell S, Didriksen M, Nawaz MS, Schandra N, Stefani A, Högl B, Dauvilliers Y, Bachmann CG, Kemlink D, Sonka K, Paulus W, Trenkwalder C, Oertel WH, Hornyak M, Teder-Laving M, Metspalu A, Hadjigeorgiou GM, Polo O, Fietze I, Ross OA, Wszolek ZK, Ibrahim A, Bergmann M, Kittke V, Harrer P, Dowsett J, Chenini S, Ostrowski SR, Sørensen E, Erikstrup C, Pedersen OB, Topholm Bruun M, Nielsen KR, Butterworth AS, Soranzo N, Ouwehand WH, Roberts DJ, Danesh J, Burchell B, Furlotte NA, Nandakumar P; 23andMe Research Team; D.E.S.I.R. study group; Earley CJ, Ondo WG, Xiong L, Desautels A, Perola M, Vodicka P, Dina C, Stoll M, Franke A, Lieb W, Stewart AFR, Shah SH, Gieger C, Peters A, Rye DB, Rouleau GA, Berger K, Stefansson H, Ullum H, Stefansson K, Hinds DA, Di Angelantonio E, Oexle K, Winkelmann J. Schormair B, et al. Nat Genet. 2024 Jun;56(6):1090-1099. doi: 10.1038/s41588-024-01763-1. Epub 2024 Jun 5. Nat Genet. 2024. PMID: 38839884 Free PMC article.
  • A survey-based approach on restless legs syndrome: practices and perspectives among Italian neurologists.
    Antelmi E, Mingolla GP, Mogavero MP, Ferri R, Lanza G, Morgante F, Bonetto C, Conte A, Ferini-Strambi L, Plazzi G, Berardelli A, Tinazzi M. Antelmi E, et al. J Neurol. 2024 Jul;271(7):4227-4236. doi: 10.1007/s00415-024-12356-7. Epub 2024 Apr 12. J Neurol. 2024. PMID: 38607430
  • Restless legs syndrome variants: A systematic review.
    Haghshenas M, Veisani Y, Sahebi A. Haghshenas M, et al. Heliyon. 2024 Mar 27;10(7):e28896. doi: 10.1016/j.heliyon.2024.e28896. eCollection 2024 Apr 15. Heliyon. 2024. PMID: 38596027 Free PMC article.
  • Correlates of Restless Legs Syndrome in Older People.
    Szklarek M, Kostka T, Kostka J. Szklarek M, et al. J Clin Med. 2024 Feb 28;13(5):1364. doi: 10.3390/jcm13051364. J Clin Med. 2024. PMID: 38592261 Free PMC article.
  • Restless legs syndrome in chronic renal failure patients on dialysis.
    van Tonder CB, Joubert G, Moodley A. van Tonder CB, et al. Afr Health Sci. 2023 Sep;23(3):764-777. doi: 10.4314/ahs.v23i3.88. Afr Health Sci. 2023. PMID: 38357105 Free PMC article.
See all "Cited by" articles

References

    1. Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisir J. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology: a report from the Restless Legs Syndrome Diagnosis and Epidemiology Workshop at the National Institutes of Health. Sleep Med 2003;4:101–119. - PubMed
    1. Allen RP, Picchietti DL, Garcia-Borreguero D, et al. Restless legs syndrome/Willis-Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria: history, rationale, description, and significance. Sleep Med 2014;15:860–873. - PubMed
    1. Winkelmann J, Polo O, Provini F, et al. Genetics of restless legs syndrome (RLS): state-of-the-art and future directions. Mov Disord 2007;22(suppl 18):S449–S458. - PubMed
    1. Winkelmann J, Schormair B, Lichtner P, et al. Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions. Nat Genet 2007;39:1000–1006. - PubMed
    1. Stefansson H, Rye DB, Hicks A, et al. A genetic risk factor for periodic limb movements in sleep. N Engl J Med 2007;357:639–647. - PubMed

MeSH terms