The specific causes of restless leg syndrome (RLS) are unknown. The condition appears to arise when nerves that use the neurotransmitter dopamine to controls movement become damaged. When onset occurs before age 40, RLS often runs in families, suggesting heredity is a factor. Five different genes are now known to be associated with RLS. One of the possible genetic variations that increase the risks of RLS is also associated with decrease serum ferritin, the protein that stores iron. One possible cause of RLS is an iron deficiency in the brain, which is believe to affect the dopamine-producing cells in particular.
In other cases, disease may lead to nerve damage in the legs. Although clinical evidence is not yet clear, some conditions that may be the causes of restless leg syndrome. Among these are:
- Pregnancy, particularly during the last trimester, especially if there is iron deficiency
- Peripheral neuropathy is often cited but the evidence is inconclusive except in hereditary neuropathies
- Iron deficiency
- Kidney failure
- Rheumatologic disorders such as rheumatoid arthritis (RA) and Sjögren’s syndrome
- Multiple sclerosis
- Parkinson’s disease (probably as a side effect of dopamine therapy in this disease)
Some factors can trigger or worsen symptoms, but may or may not be underlying causes of RLS. These include medications such as cold-and-allergy remedies that have antihistamines, antidepressants and anti-psychotics, and anti-nausea drugs. Alcohol and lack of sleep also may play a role.