Further evidence that painful and painless restless legs syndrome are contrasting phenotypes: a study of adult twins and their families.

OBJECTIVE

We aimed to test in adults that painful and painless phenotypes of the restless legs syndrome (RLS) differed in genetic influence and associations with comorbidities.

METHODS

Twins Research Australia administered questionnaires to adult twins and their families. Responders self-reported RLS (Cambridge-Hopkins diagnostic questionnaire) and painful and painless subsets, their history of doctor-confirmed iron deficiency, selected primary and chronic pain conditions, and medical conditions known to be associated with RLS. Association analyses were conducted using logistic regression, applying generalised estimating equations, adjusted for gender and age.

RESULTS

Responders to the RLS diagnostic questionnaire and pain questions comprised 1449 adults (64.4 % females). Responders to questions about history of iron deficiency comprised 1327 adults (65.7 % females). There were insufficient dizygous twins, particularly those with painful RLS, for some aspects of heritability testing. Painless, but not painful, RLS was associated with history of iron deficiency. There were no associations between painless RLS and pain conditions. Painful RLS was associated with migraine, recurrent abdominal pain, growing pains, diverse chronic pain, chronic spinal pain, and dysmenorrhea. Both painless and painful RLS were associated with anxiety and depression. Painful RLS numbers were insufficient for analyses with other general medical conditions. Painless RLS was associated with obesity, Parkinson disease, ADHD, hypertension, and vitamin D deficiency.

CONCLUSIONS

We confirmed in adults that painful and painless RLS phenotypes have contrasting associations. Painless RLS was significantly associated with history of iron deficiency and general medical conditions, while painful RLS was associated with multiple primary and chronic pain conditions.