Clinical characteristics of childhood-onset restless legs syndrome (RLS) were studied in 32 (5.9%) patients, <18 years of age, diagnosed with the disorder among 538 who attended the Pediatric Sleep Disorders Center with sleep-wake complaints, between January 2000 and March 2004, at the Mayo Clinic, Rochester, MN. Subjects with RLS were classified as probable (9/32 [28%]) or definite (23/32 [72%]). The age of diagnosis was earlier in the probable group (11.3 years; range 6-15) than the definite group (13.9 years; range 5-17; p=0.04), but otherwise, no differences were found between the two groups. All patients met the diagnostic criteria for RLS as defined by the National Institutes of Health workshop . These include an urge to move the legs, accompanied by unpleasant sensation in the legs, worsened by periods of inactivity, relieved by movement, occurring mainly at night, complicated by sleep disturbance, and a positive family history. The average duration of follow-up was 12.3 months (range 1-44). Sleep onset or sleep maintenance insomnia was the most common complaint occurring in 28 of 32 (87.5%) patients, inattentiveness was present in 25%, limb movements observed during sleep as a presenting symptom in 31%, chronic fatigue in 28%, and sleep walking in 9.3%. A positive family history of RLS in first-degree relatives was obtained in 23 of 32 subjects (71%); mothers were affected more often than fathers (17/23 cf 6/23;p=0.02). Serum ferritin levels, available in 24 of 32 subjects, were below the 5th percentile for age and sex in 8 (33%) (5th percentile norms in 10-year-old boys are 24mcg/L and in adolescent girls 8mcg/L); and below the median (23 mcg/L in males and 17 mcg/L in females) in 18 (75%); 20 (83%) subjects had levels below 50 mcg/L (normal median values range from 29 to 52mcg/L). Hematocrit was below the reference range in 5 of 23 subjects (mean 33.9; range 32.8-35). The mean Periodic Limb Movement Index (PLMI) in 24 subjects was 17.3 and greater than 5 in 16 (67%). Sleep was improved by pharmacotherapy in 18 of 29 (62%) subjects (pramipexole [dopamine receptor agonist], oral iron, gabapentin, clonazepam, or carbidopa-L-dopa) and unchanged in 4 (14%); in 7 the response was unknown. 
COMMENT. Restless legs syndrome (RLS) occurs in two forms, primary and secondary. The primary form has an early age of onset and is inherited as a single, autosomal dominant genetic disorder with a predilection for maternal transmission. In the above study, mothers were affected three times more often than fathers. The secondary form occurs in association with iron deficiency, anemia, pregnancy, renal failure, Charcot-Marie Tooth type 2 disease, spinocerebellar ataxia, and Parkinson disease . A decrease in serum ferritin levels is a significant feature of RLS, previously described in teenagers  and adults  with RLS. Oral iron therapy may result in improved sleep-wake function and relief of RLS (Kryger et al, 2002) . Decreased serum ferritin levels are not always associated with low hematocrit or low red cell mean corpuscular volume; anemia is a late finding, when the serum ferritin has fallen below 10 mcg/L . Adolescent girls may be at greater risk of exacerbation of RLS because of lower iron stores during menstruation. Serum ferritin measurements are an important diagnostic aid in childhood-onset RLS, and oral iron therapy may be of benefit in therapy.
RLS may occur in association with attention deficit hyperactivity disorder (ADHD) , and both daytime and nighttime behavioral symptoms need to be addressed in the workup of RLS. Inattention was noted as a feature in 25% of RLS cases reported from the Mayo Clinic. Periodic limb movements in sleep (PLMs) are another comorbid disorder, occurring in association with childhood RLS, ADHD and sleep disorders (Picchietti et al, 1999). PLMs consist of extension of the big toe, similar to a Babinshi sign, flexion of the foot, and an abrupt extension of the limb. These repetitive, stereotyped movements, associated with sleep disorders, on arousal or awakening, are frequently overlooked by parents and physicians, they are diagnosed by polysomnography, and they can occur independently of RLS . Both RLS and PLM respond to treatment with the dopamine agonist pramipexole.
Cabergoline treatment in RLS. The dopamine agonist cabergoline (CAB) was effective in the treatment of 85 adults (71% females) with RLS in a double-blind, placebo-controlled, multicenter trial followed by an open long-term extension trial of 47 weeks . Augmentation or worsening of symptoms, unique to dopaminergics, occurs less often with cabergoline than with shorter acting drugs (9% cf 30% with pramipexole). Cabergoline has a half-life of up to 65 hours, and is currently approved for treatment of adults with Parkinsonism. Pramipexole is currently considered the first line of treatment for idiopathic RLS.