DESCRIPTION (provided by applicant): The goal of this project is to find and characterize the gene or genes responsible for familial restless legs syndrome (RLS). Restless legs syndrome is a common disorder, affecting up to 10-15% of the population, and is frequently inherited. RLS consists of an uncomfortable feeling in the legs, occurring at rest, which worsens in the evenings and is partially relieved by movement. Several large Utah families with RLS have participated in our previous preliminary studies to date. We propose to differentiate between inherited RLS and RLS secondary to several common medical illnesses by a thorough history and neurological exam, commonly available blood tests to exclude those medical conditions, and a Suggested Immobilization Test (SIT). The SIT test has been shown to be both sensitive and specific for the RLS syndrome. We then plan to perform linkage analysis on the banked DNA, identify candidate genes from the promising regions using the Human Genome Project database, and screen for causative mutations in these candidate genes. RLS symptoms are often relieved by dopaminergic medications. Finding the genes involved in RLS may enlighten us about the neurochemistry of other disorders involving dopamine, including Parkinson's disease. Storage of iron in the brains of persons with RLS is lower than unaffected people, suggesting an interconnection between development of iron stores, dopamine pathways and RLS symptoms. RLS incidence increases with age, but is not a neurodegenerative disorder. Understanding RLS may improve our understanding of brain maturation and aging, and circadian rhythms. RLS affects about 1 in 10 people, and becomes more common with increasing age. It can be caused by several common medical conditions, but is frequently inherited. Persons with RLS often pace at night to relieve their symptoms, suffer from lack of sleep, and are sleepy during the daytime due to RLS. This adversely affects their productivity at work and their quality of life at home.