ABSTRACT
Restless legs syndrome (RLS) is extremely common, affecting between 5% and 10% of Caucasian populations, although it appears less common in Asian and African populations (1). In roughly 60% of cases, a family history of RLS can be found, although this is often not initially reported by the patient (2). Three gene loci have been published, although specific causative proteins remain elusive (3-5). Given the wide distribution of RLS; however, it is likely that additional specific genetic etiologies are yet to be discovered. Despite the appropriate attention given to RLS genetics, between 2% and 6% of the population probably suffer from RLS without any identifiable highly penetrant genetic pattern. It is not known whether some ‘‘genetic’’ forms of RLS could express low penetrance, and mimic a sporadic pattern of onset. Therefore, patients without a positive family history are classified as either primary RLS, if no other explanation is found, or secondary RLS, if they concurrently posses a condition known to be associated with RLS. Because the exact pathophysiology of RLS is unknown, the relationship between ‘‘idiopathic’’ RLS and ‘‘secondary’’ RLS is not elucidated in any case. It is not known why some persons with an associated medical condition develop RLS symptoms while others, usually most others, do not. Furthermore, it is not established whether persons with a genetic predisposition for RLS may be symptom free without an additional insult caused by an associated condition, or if subclinical or mild genetic RLS is exacerbated by the coincidental occurrence of a secondary cause.
