Prevalence rates of RLS increase steadily with age until about age 60 years, with symptoms remaining stable or decreasing slightly in older age groups. Compared with nonfamilial cases, familial RLS usually has a younger age at onset and a slower progressive course. The clinical course of RLS differs by age at onset. When onset occurs before age 45, there is of— ten a slow progression of symptoms. In late-onset RLS, rapid progression is typical, and aggravating factors are common. Symptoms of RLS appear similar across the lifespan, re- maining stable or decreasing slightly in older age groups.
Diagnosis of RLS in children can be difficult because of the self—report component.
While Criterion A for adults assumes that the description of ”urge to move" is by the pa- tient, pediatric diagnosis requires a description in the child’s own words rather than by a parent or caretaker. Typically children age 6 years or older are able to provide detailed, ad— equate descriptors of RLS. However, children rarely use or understand the word "urge," reporting instead that their legs ”have to” or ”got to" move. Also, potentially related to prolonged periods of sitting during class, two-thirds of children and adolescents report daytime leg sensations. Thus, for diagnostic Criterion A3, it is important to compare equal duration of sitting or lying down in the day to sitting or lying down in the evening or night.
Nocturnal worsening tends to persist even in the context of pediatric RLS. As with RLS in adults, there is a significant negative impact on sleep, mood, cognition, and function. Im- pairment in children and adolescents is manifested more often in behavioral and educa- tional domains.
Genetic and physiological. Predisposing factors include female gender, advancing age, genetic risk variants, and family history of RLS. Precipitating factors are often time- limited, such as iron deficiency, with most individuals resuming normal sleep patterns after the initial triggering event has disappeared. Genetic risk variants also play a role in
RLS secondary to such disorders as uremia, suggesting that individuals with a genetic sus- ceptibility develop RLS in the presence of further risk factors. RLS has a strong familial component.
There are defined pathophysiological pathways subserving RLS. Genome-wide asso- ciation studies have found that RLS is significantly associated with common genetic vari- ants in intronic or intergenic regions in MEISI, BTBD9, and MAP2K5 on chromosomes 2p, 6p, and 15q, respectively. The association of these three variants with RLS has been inde- pendently replicated. B TBD9 confers a very large (80%) excessive risk when even a single allele is present. Because of the high frequency of this variant in individuals of European descent, the population attributable risk (PAR) approximates 50%. At-risk alleles associ- ated with MEISI and BTBD9 are less common in individuals of African or Asian descent, perhaps suggesting lower risk for RLS in these populations.
Pathophysiological mechanisms in RLS also include disturbances in the central dopa- minergic system and disturbances in iron metabolism. The endogenous opiate system may also be involved. Treatment effects of dopaminergic drugs (primarily D2 and D3 non- ergot agonists) provide further support that RLS is grounded in dysfunctional central dopaminergic pathways. While the effective treatment of RLS has also been shown to sig- nificantly reduce depressive symptoms, serotonergic antidepressants can induce or aggra- vate RLS in some individuals.
Although RLS is more prevalent in females than in males, there are no diagnostic differ- ences according to gender. However, the prevalence of RLS during pregnancy is two to three times greater than in the general population. RLS associated with pregnancy peaks during the third trimester and improves or resolves in most cases soon after delivery. The gender difference in prevalence of RLS is explained at least in part by parity, with nullipa- rous females being at the same risk of RLS as age—matched males.