[Restless legs syndrome: a genetic disease?]

Abstract

Restless legs syndrome (RLS) is characterized by an unpleasant sensation in the lower limbs and an urge to move, occurring during periods of rest, in the evening and during the night and improved by movement. There are two different phenotypes of RLS: an early-onset form, starting before 36 years old with mostly a familial history, being mostly severe and highly genetically determined, with a high dependence to iron brain levels; a delayed-onset form, starting after 36 years old, mostly secondary, without familial history, with a rapid evolution in two or three years, and with frequent low ferritine serum levels. The primary form of RLS is associated with a familial history in 40 to 92 % of the patients. Monozygotic twins have a 54 to 83 % concordance rate for RLS phenotype. Linkage association studies have identified eight loci involved in the familial transmission of the disease. Genetic association studies have identified allelic variants responsible for a 50 % increased risk to develop RLS in the general population. Proteins coded by some implicated genes are involved in the development of spinal motor neurons and spinal dorsal horns, and in brain iron homeostasis.