Defining the phenotype of the restless legs syndrome (RLS) using age-of-symptom-onset

Objective: RLS varies considerably in both frequency of occurrence in a family and in age of onset of symptoms. Patients whose RLS symptoms start before or at age 45 have many more affected relatives than those whose symptoms start later, suggesting etiological differences. When etiology differs, factors affecting severity may differ. This study compares the effects of current age and serum ferritin on RLS severity for early- and late-onset (over 45) RLS.Design and methods: RLS severity was evaluated using a validated clinical severity scale and sleep efficiency on a standard polysomnogram. Data from 26 consecutive RLS patients (14 early- and 12 late-onset) who met study criteria were analyzed.Results: Age-of-onset groups showed no significant differences in age, gender and RLS symptom severity. Regression analyses showed significant (P<0.05) differences with RLS severity primarily affected by age for early-onset RLS and by serum ferritin for late-onset RLS.Conclusions: The age effect for early-onset RLS indicates a slowly progressive disorder. Thus early-onset RLS appears to occur commonly in families, slowly progress with age and have a limited relation to serum iron status. In contrast, late-onset RLS appears to occur less commonly in families, rapidly progress with age and have a strong relation to serum iron status. Age of symptom onset should be considered to better define the RLS phenotype in future studies.