Researchers have found two new genetic regions associated with an increased risk of restless legs syndrome (RLS). People with specific genetic variations in these regions or other previously identified genes linked to RLS are more likely to develop the disorder.

Restless legs syndrome is one of the most common neurological disorders, affecting up to 10% of people over age 65. The condition causes tingling, prickling, and numbness in the legs with an urge to move them that occurs mainly when the body is at rest, usually at night.

These symptoms can only be relieved through movement, which frequently leads to chronic sleep loss, daytime sleepiness, and depression.
New Genetic Link for RLS

In the study, published in PLoS Genetics, researchers compared the genes associated with restless legs syndrome in 922 people with the disorder and a comparison group of 1,526 healthy people. They then replicated their findings of 76 potential candidate genes in 3,935 people with restless legs syndrome and 5,754 healthy people.

That narrowed the results to six genetic regions associated with an increased risk of developing restless legs syndrome. Four of these mutations have been previously reported, and two are new.

One of the newly identified genetic regions, TOX3, is involved in regulating brain activity. Previous studies have shown that increased levels of the TOX3 protein protects brain cells from cell death, but the link between TOX3 and restless legs syndrome is not clear.

Researcher Juliane Winkelmann of the Institute of Human Genetics in Munich, Germany, and colleagues say the findings will help enable further research into the causes of restless legs syndrome and developing new treatments.