Clinical phenotype and genetics of restless legs syndrome.

Restless legs syndrome (RLS) is a common neurologic disorder classically characterized by dysesthesias affecting the legs, which are precipitated by rest or inactivity and relieved by movement. A circadian preponderance for the evening and night leads to sleep disturbances. RLS can present as a primary form, often with familial aggregation, or a secondary form due to other underlying conditions. Dopaminergics such as levodopa or dopaminagonists represent first-line therapeutic options whereas opioids and antiepileptics serve as second-line options in difficult-to-treat cases. From the days of its first modern description by Swedish neurologist Karl Ekbom in 1945, a significant genetic influence on the RLS phenotype has been recognized. Over the past 2 decades, family studies have identified several linkage loci for RLS but no underlying genetic variants have been pinpointed. However, genome-wide association studies have highlighted a total of seven loci at which common genetic variants contribute to disease susceptibility, but the way these loci fit into the bigger picture of RLS pathogenesis is just beginning to be uncovered