Studies of penetrance and anticipation in five autosomal-dominant restless legs syndrome pedigrees.

Restless legs syndrome (RLS) can occur with an autosomal-dominant mode of inheritance. To determine if there are distinguishing features of RLS pedigrees which might clarify molecular mechanisms of pathogenesis, five pedigrees with 81 affected members were analyzed for age of onset, sex ratio, and transmission pattern. One-factor analysis of variance of ages of onset between generations was carried out, and segregation ratios were calculated for each generation. These kindreds showed an autosomal-dominant mode of inheritance and a male:female ratio of 1:1.4 (p = 0.15). One of the five analyzed pedigrees shows some evidence of reduced penetrance. In two of the five analyzed pedigrees, there is statistical support for anticipation (p<0.05). These variations in penetrance and anticipation suggest possible genetic heterogeneity.

Periodic limb movement disorder and restless legs syndrome in children with attention-deficit hyperactivity disorder.

Sleep disruption can lead to symptoms of attention-deficit hyperactivity disorder (ADHD) in children. Since periodic limb movement disorder and/or restless legs syndrome can cause sleep disruption, we assessed whether these two specific sleep disorders are likely to occur in children with ADHD. We asked a series of 69 consecutive parents of children with ADHD questions about the symptoms of periodic limb movement disorder. Based on a positive response to these periodic limb movement disorder queries, 27 children underwent all-night polysomnography. Eighteen children (aged 2 to 15 years) of the 27 (26% of the 69 children with ADHD) had 5 or more periodic leg movements in sleep per hour of sleep and had complaints of sleep disruption, thus fulfilling the criteria for periodic limb movement disorder. A comparably age- and sex-matched group of children referred to a sleep laboratory for sleep complaints but without ADHD showed only a 5% prevalence (2 of 38 subjects) of periodic leg movements in sleep (P=.017). Eight of the 18 children with ADHD and periodic limb movement disorder and one of the two control patients with periodic limb movement disorder had both a personal and parental history of restless legs syndrome symptomatology. This study further documents the occurrence of periodic limb movement disorder and restless legs syndrome in children and is the first large-scale study establishing a possible comorbidity between ADHD and periodic limb movement disorder. We propose that the sleep disruption associated with periodic limb movement disorder and restless legs syndrome and the motor restlessness of restless legs syndrome while awake could contribute to the inattention and hyperactivity seen in a subgroup of ADHD-diagnosed children.

A questionnaire study of 138 patients with restless legs syndrome: the 'Night-Walkers' survey.

After verifying the diagnosis of restless legs syndrome (RLS) in 105 patients who are part of a nationwide support group, we undertook a telephone survey of their symptomatology. We then compared the answers with those of 33 of our own RLS patients who had undergone a neurologic examination and had a periodic limb movement in sleep (PLMS) index of > 5 (number per hours of sleep). Although RLS has generally been considered to be a condition of middle to older age, the results for the support group, and for our patients, are similar in that more than a third of the patients in each group experienced their first symptoms before the age of 10. Initial lack of diagnosis or misdiagnosis by a physician were common and the symptoms were commonly thought to be psychogenic whatever the age of onset. In some cases, young age-onset RLS was severe from the start. For younger age-onset patients whose symptoms were severe enough to seek immediate medical attention, confounding or misdiagnosis included "growing pains" and attention deficit hyperactivity disorder. However, medical attention was generally not sought until the fourth decade. Most respondents stated that this was because their symptoms were mild at onset and then progressed. In the older age-onset patients, misdiagnoses also included skin irritation, arthritis, and malingering. A total remission of symptoms of a month or more was present in at least 15% of the individuals in all groups surveyed. More than 50% of the respondents know of one or more first-degree relatives affected by RLS. Five of our 33 patients had RLS initially triggered either by diabetic peripheral neuropathy or lumbosacral radiculopathy.