Genetics of Restless Legs Syndrome: Mendelian, Complex, and Everything in Between

Restless legs syndrome (RLS) is a common sleep-related movement disorder with a significant genetic contribution as evidenced by heritability of 50% to 60%. The view of the underlying genetic architecture evolved from that of a mendelian disease with an autosomal-dominant mode of inheritance to that of a complex multifactorial disorder with both genetic and nongenetic factors contributing to the susceptibility. Family based linkage studies and population-based association studies have identified genomic loci containing causally related genes and variants. However, the actual etiologic variants and their role in RLS pathophysiology still remain to be determined.