Restless legs syndrome (RLS) is a sleep-related movement disorder that affects up to 15 % of the population. Linkage studies have identified several genomic loci in single families (12q, 14q, 9p, 2q, 20p and 16p, respectively). However, confirmation of these loci has not always been achieved, and causative mutations have not yet been identified. The locus on chromosome 2q33 (RLS4) was identified in two South Tyrolean families who shared a haplotype of microsatellite marker alleles across an 8.2-cM region. To pinpoint the gene localisation within RLS4, additional families from the same geographic region were evaluated, and linkage was replicated in one family. Within the candidate region, we initially found a haplotype of 23 single nucleotide polymorphism markers spanning 131.6 Kb shared by all affected members of the three linked families. Using a next generation sequencing approach, we further restricted the shared candidate region to 46.9 Kb over the potassium channel-related gene KCTD18 and exons 10-13 of SPATS2L.