cially in the evening and at night, causing most individuals difficulty falling asleep (Michaud et al., 2000). The discomfort associated with RLS also causes individuals to wake frequently during the night (Montplaisir et al., 1997). Individuals with RLS often experience periodic limb movements; however, periodic limb movement disorder (see below) is not always associated RLS (Michaud et al., 2000).

The prevalence of RLS has been reported to be at minimum 5 percent (Lavigne and Montplaisir, 1994; Rothdach et al., 2000; NSF, 2005a; Montplaisir et al., 2005; Phillips et al., 2006), which makes it one of the most common movement disorders and sleep disorders. This condition may be found in in adolescents and teenagers (Kryger et al., 2002a) and is more common in older adults and females (Rothdach et al., 2000; Allen and Earley, 2001; Nichols et al., 2002), affecting over 20 percent of pregnant women. RLS symptoms associated with pregnancy are caused by transient low levels of ferritin and folate; therefore, they typically disappear within 4 weeks after delivery (Lee et al., 2001).

RLS may also be associated with attention-deficit hyperactivity disorder (ADHD). In a cross-sectional survey of 866 children, ADHD symptoms were almost twice as likely to occur with symptoms of RLS as would be expected by chance alone (Chervin et al., 2002).

Etiology and Risk Factors

The exact cause of RLS is not completely understood. It likely results from altered dopamine and iron metabolism, and there is evidence for a genetic contribution. More than 50 percent of idiopathic cases are associated with a positive family history of RLS (Ekbom, 1945; Walters et al., 1996; Montplaisir et al., 1997; Winkelmann et al., 2002; Allen et al., 2003), and these cases segregate in an autosomal dominant fashion with high penetrance (90 to 100 percent) (Winkelmann et al., 2002). Susceptibility gene loci have been identified on chromosomes 12q (Desautels et al., 2001), 14q (Bonati et al., 2003), and 9p (Chen et al., 2004); however, no genetic markers or abnormalities have been identified.

RLS commonly occurs in individuals with iron deficiency, including end-stage renal disease, iron-deficiency anemia, pregnancy, and gastric surgery. Iron deficiency, for example caused by repeated blood donation, may also be associated with RLS (Silber et al., 2003; Ulfberg and Nystrom, 2004; Kryger et al., 2003). It is hypothesized that low levels of iron impair transmission of dopamine signals, which contributes to RLS. Iron levels are reduced in the substantia nigra (Allen et al., 2001; Connor et al., 2003), which is a region of the brain responsible for controlling voluntary movement through neurons that rely on dopamine to communicate with each other. The iron deficiency is consistent with abnormal regulation of the transferrin



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