The Molecular Genetics of Restless Legs Syndrome

Restless legs syndrome (RLS) is a common sensorimotor trait defined by symptoms that interfere with sleep onset and maintenance in a clinically meaningful way. Nonvolitional myoclonus while awake and asleep is a sign of the disorder and an informative endophenotype. The genetic contributions to RLS/periodic leg movements are substantial, are among the most robust defined to date for a common disease, and account for much of the variance in disease expressivity. The disorder is polygenic, as revealed by recent genome-wide association studies. Experimental studies are revealing mechanistic details of how these common variants might influence RLS expressivity.