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Genetics of Restless Legs Syndrome (RLS)

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Movement Disorder Genetics

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Abstract

Restless legs syndrome (RLS) is a complex genetic disease characterized by dysesthesias primarily affecting the lower limbs, which are precipitated by rest and classically occur at night. Movement of the affected extremity leads to prompt symptom relief. Genetically, RLS is a complex disorder with a heritability of up to 60 %. While linkage analyses were largely unsuccessful, genome-wide association studies (GWAS) have identified six genomic loci, to date, which harbor common genetic variants associated with an increased risk for RLS. At least one of these regions also harbors rare variants, which contribute to the genetic architecture of the disease. The first functional follow-up studies in the post-GWAS era have implicated expression alterations and forebrain development as well as dysfunctional iron metabolism as the possible downstream effects of the RLS-associated genetic alterations.

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Authors and Affiliations

  1. Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich, 81675, Germany

    Eva C. Schulte MD, PhD & Juliane Winkelmann MD

  2. Neurologische Klinik und Poliklinik, Institut für Humangenetik, Helmholtz Zentrum München, Munich, 81675, Germany

    Eva C. Schulte MD, PhD

  3. Institute of Neurogenomics, Helmholtz Zentrum München, Munich, Germany

    Juliane Winkelmann MD

  4. Munich Cluster for Systems Neurology (SyNergy), Munich, Germany

    Juliane Winkelmann MD

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  1. Eva C. Schulte MD, PhD
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  2. Juliane Winkelmann MD
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Correspondence to Juliane Winkelmann MD .

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Editors and Affiliations

  1. Department of Neurology, University Hospital Kiel, Kiel, Germany

    Susanne A. Schneider

  2. Department of Molecular Neuroscience, University College London, Institute of Neurology, London, United Kingdom

    José M. Tomás Brás

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Schulte, E.C., Winkelmann, J. (2015). Genetics of Restless Legs Syndrome (RLS). In: Schneider, S., Brás, J. (eds) Movement Disorder Genetics. Springer, Cham. https://doi.org/10.1007/978-3-319-17223-1_15

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  • DOI: https://doi.org/10.1007/978-3-319-17223-1_15

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