LAUSR

Several studies characterized painful and painless restless legs syndrome (RLS) phenotypes based on clinical, topographical, polysomnographic, and genetic background. One pediatric twin family study demonstrated a clear contrast between these two forms of RLS. The painful pediatric RLS being familial, probably genetically influenced, and associated with primary pain disorders (non-migraines headaches; recurrent abdominal pain), the painless pediatric RLS being familial but probably not genetically determined, and associated with iron deficiency, female gender, and persistent/chronic pain disorders. The current study investigated these contrasting painful and painless RLS phenotypes in the adult population. The Twins Research Australia database was used to recruit adult twins and their families. The subjects were surveyed and responded to questions related to their demographics, the Cambridge-Hopkins diagnostic questionnaire for RLS diagnosis and categorization into painful and painless RLS subgroups, the history of physician-confirmed iron deficiency, the presence of selected chronic and primary pain disorders, and also other medical, non-pain conditions associated with RLS. Association analyses, using logistic regression with application of generalized estimating equations to control for twin influences, and adjusting for gender and age, were conducted. A total of 1449 adult subjects responded to the RLS diagnostic questionnaire and to pain related and other medical conditions questions (64.4% females). A total of 1327 adult subjects responded to the iron deficiency pertinent questions (65.7% females). Numbers of dizygous twins and painful RLS subjects were insufficient for heritability testing and for association analyses with medical conditions. Painless RLS was associated with iron deficiency (OR= 1.59; p=0.003), while painful RLS was not (OR=1.26; p=0.444). Painful RLS was associated with migraine (OR=2.35; p=0.004), recurrent abdominal pain (OR=1.96; p=0.026), growing pains (OR=2.13; p=0.050), diverse chronic pain (OR=2.88; p=0.017), chronic spinal pain (OR=3.65; p=0.001) and dysmenorrhea (OR=2.46; p=0.009). Painless RLS was not associated with any pain disorder. This study further confirmed contrasting associations in adults with painless and painful phenotypes of RLS (association with iron deficiency and multiple pain disorders, respectively). This work was supported by the School of Women's and Children's Health, Medicine, University of New South Wales, Kensington 2052, NSW, Australia; Private donors.