reported RLS in 12% of those studied and found a higher prevalence in women and in older people (Kim et al 2005). RLS can cause significant distress Severe RLS is a deeply unpleasant condition. In a study of the impact on quality of life of sufferers (using the Short Form-36 Health Survey), RLS had a similar effect to other chronic disorders, such as type 2 diabetes, and clinical depression (Allen et al 2005). RLS may require a considerable restriction of lifestyle as a result of intolerable symptoms during long airplane or car journeys, lectures or visits to the cinema. One or more aspects of the condition may be particularly troublesome for individual patients. As part of the REST primary care study, 182 patients with RLS were asked about their symptoms (Hening et al 2004). The most troublesome symptoms reported were sleep disturbance (39%), followed by uncomfortable feelings in the legs (27%), pain (22%) and inability to stay still and urge to move the legs (11%). Thus, sleep disturbance, subsequently causing disturbance of day-time functioning in many, are of particular significance to RLS patients. This is not surprising since severe RLS produces the most extreme chronic sleep loss of any sleep disorder. There are multiple reasons for this. In the REST study, almost 70% of sufferers reported a sleep latency (the time to get to sleep) of 30 minutes or longer, which is considered to be in the insomnia range. On a poor night, 50% reported less than 5 hours sleep and 14% got less than 3 hours sleep. Almost 60% reported that they wake three or more times a night so that sleep is significantly fragmented. Other daytime symptoms reported by patients included fatigue in 60% and difficulty concentrating in 50%. However, RLS patients do not report the same degree of daytime sleepiness or the risk of accidents that have been found, for example, in the sleep apnoea population. This may be due to the restlessness, with arousal and activity, intrinsic to the condition. The fragmentation of sleep may result from the RLS itself or from accompanying periodic limb movements of sleep (PLMS) (Trenkwalder, Walters, et al 1996). PLMS are semirhythmic movements of the limbs which last a few seconds and occur at regular intervals. The most frequent movement seen is dorsiflexion of the great toe (similar to the Babinski response), with flexion of the knee, hip, and occasionally elbow. PLMS can occur in otherwise healthy people and are especially common in old age. In RLS, they are almost always present, are often very intense and can cause arousals and awakenings. Some RLS patients do not Therapeutics and Clinical Risk Management 2006:2(4) Restless leg syndrome get symptoms until they have been asleep for a while; they wake up, perhaps because of the PLMS, and develop the fidgety sensations of RLS and have to get up and walk for a while before they can return to sleep. RLS is a chronic disorder. In the Hopkins family study, the average duration of symptoms in 66 RLS patients was 30 years (n=66) (Allen et al 2002). In general, symptoms tend to progress with advancing age, although there is considerable individual variability. RLS may be symptomatic of an underlying condition RLS can generally be divided into primary and secondary forms. RLS is primary (idiopathic) in most cases, and up to half of these patients have a positive family history (Trenkwalder, Seidel, et al 1996). RLS may also develop secondary to a variety of conditions, although, since RLS is a common condition, many of the associations suggested by case reports remain unproven. Secondary causes of RLS are more common in those who develop the condition for the first time in later life, occurring in over 70% of those with onset at 65 years or more, while a positive family seems most common those with early-onset RLS (O’Keeffe 2005). Genetics of RLS The mode of inheritance of RLS seems to be autosomal dominant. There is a high concordance rate (83%) for RLS symptoms in monozygotic twins (Ondo et al 2002) although expression of RLS can vary between twins and within families. Age-dependent penetrance of RLS has been reported, with full penetrance by the age of 60 (Winkelmann 2002). Anticipation, an earlier age of onset in later generations, has also been reported (Trenkwalder, Seidel, et al 1996). Susceptibility loci have been described on chromosome 12q in a French-Canadian family (Desaultels et al 2001), on chromosome 14q in an Italian family (Bonati et al 2003) and on chromosome 9p in North American families (Chen et al 2004). It seems increasingly likely that multiple genes influence the development of RLS, perhaps interacting with environmental factors. Secondary RLS The most important secondary form of RLS is the association with iron deficiency (with or without anemia) which is present in up to a third of RLS patients (Ekbom 1960; O’Keeffe et al 1993), including those presenting in childhood pains (Kotagal and Silber 1999). Serum ferritin is accepted as the best screening test for iron deficiency, 469