Recent advances in the diagnosis, genetics and treatment of restless legs syndrome

J Neurol. 2009 Apr;256(4):539-53. doi: 10.1007/s00415-009-0134-9. Epub 2009 Apr 27.


Knowledge of restless legs syndrome (RLS) has greatly increased in recent years due to the many advances that have been made in diagnosis, management and genetics. Tools have been developed that facilitate the diagnosis and treatment of RLS, in particular the essential diagnostic criteria for RLS have been refined, severity scales (IRLS, RLS-6, JHSS) have been developed, as have instruments that improve diagnostic accuracy and assess for specific aspects of RLS such as augmentation. These newly developed tools have been used in recent population-based studies, which have provided a greater understanding of the epidemiology of RLS, and also within patient-based trials. As far as the genetics of RLS is concerned, linkage studies in RLS families have revealed eight loci but no causally related sequence variant has yet been identified using this approach. Recent genome-wide association studies have identified variants within intronic or intergenic regions of MEIS1, BTBD9, and MAP2K5/LBXCOR1, and PTPRD, raising new pathological hypotheses for RLS. An overview on therapeutic options and recent trials is given based on evidence-based management strategies for this common disorder.

MeSH terms

  • Co-Repressor Proteins
  • Diagnosis, Differential
  • Family
  • Genetic Linkage
  • Homeodomain Proteins / genetics
  • Humans
  • MAP Kinase Kinase 5 / genetics
  • Myeloid Ecotropic Viral Integration Site 1 Protein
  • Neoplasm Proteins / genetics
  • Nerve Tissue Proteins
  • Neurologic Examination
  • Randomized Controlled Trials as Topic
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2 / genetics
  • Repressor Proteins / genetics
  • Restless Legs Syndrome / diagnosis
  • Restless Legs Syndrome / drug therapy*
  • Restless Legs Syndrome / genetics*
  • Severity of Illness Index
  • Transcription Factors / genetics


  • BTBD9 protein, human
  • Co-Repressor Proteins
  • Homeodomain Proteins
  • MEIS1 protein, human
  • Myeloid Ecotropic Viral Integration Site 1 Protein
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Repressor Proteins
  • SKOR1 protein, human
  • Transcription Factors
  • MAP Kinase Kinase 5
  • MAP2K5 protein, human
  • PTPRD protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2