Controversies and challenges in defining the etiology and pathophysiology of restless legs syndrome

Restless legs syndrome (RLS) can occur as a primary disorder, with no apparent cause other than a possible genetic predisposition, or as a secondary condition, most commonly related to iron deficiency, pregnancy, or end-stage renal disease. Recent studies have identified 2 different phenotypes of RLS based on age at onset of symptoms. Persons whose RLS symptoms start at an earlier age (<45 years) are more likely to have a family history of RLS and tend to have a more slowly progressive development of the disorder compared with individuals who have later onset of symptoms. In the past, our ability to determine either prevalence or population factors associated with increased occurrence of RLS has been limited. However, 4 different diagnostic criteria have been established. Familiarity with diagnostic criteria and clinical characteristics are essential for diagnosis and appropriate treatment, if required.