ABSTRACT
Recent advances in molecular and genetic epidemiological studies of restless legs syndrome (RLS) (MIM 102300) have led to a series of important discoveries that promise to greatly expand our knowledge of the molecular basis of this common disease. Several genetic epidemiological studies and twin studies have characterized the genetic components of RLS and suggest that it is a highly heritable trait. The accumulated evidence suggests that a single founder mutation(s) in an RLS pedigree can lead to a monogenic inheritance pattern; however, in most cases, RLS is a complex disease with mixed contributions of major genes, modifier genes, and environmental factors, reflecting its nature of genetic heterogeneity. The chromosomal positions of three putative RLS genes (9p, 12q, and 14q) have been determined by either model-based linkage analysis of single, large, and well-characterized pedigrees or model-free linkage analysis of multiple pedigrees. However, the causative or susceptibility genes within these linkage regions remain to be identified. A few population-based, case-control genetic studies have investigated several candidate genes for the pathogenesis of RLS. In this chapter, we describe these advances in the field of genetics of RLS.
