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
. 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

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

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

Publication types

MeSH terms