Genetics of restless legs syndrome

Several studies on restless legs syndrome (RLS) have suggested a substantial genetic contribution in the etiology of this sleep disorder. Clinical surveys of idiopathic RLS patients have shown that 40-90% report a positive family history. The clinical features have been compared between familial and sporadic cases and the only difference found was a younger age-at-onset in familial RLS. Despite several reports suggesting a genetic contribution to the etiology of idiopathic RLS, few molecular genetic studies have been carried out attempting to identify genes that can predispose to this disorder. In particular, genes encoding for the GABA A receptor subunits, the gene for the alpha1 subunit of the glycine receptor, and genes involved in dopaminergic transmission and metabolism have been analyzed, however no significant findings have been reported. Genomewide linkage analysis studies using microsatellite markers have identified three loci for RLS: on chromosome 12q, on chromosome 14q and on chromosome 9p. It is important to investigate whether further RLS families show linkage to one of these loci to discuss the contribution of these loci and to provide a prerequisite of a mutational screening and identification of the RLS genes.