Scientists find new genes behind 'Restless Legs Syndrome'

Scientists claim that they have made a key breakthrough by mapping certain important genes that cause restless legs syndrome (RLS), a neurological condition that is characterized by abnormal or unpleasant sensations usually occurring in the legs.

Two studies published simultaneously in the New England Journal of Medicine and in the online edition of Nature Genetics on July 19 offer new evidence that inheritance plays a role in restless leg syndrome, an uncomfortable and sometimes painful feeling in the legs, leading to sleep disorders.

The new studies, which are the first to identify specific genes responsible for the sleep-robbing neurological disorder, suggested that this common sleep disorder, affecting tens of millions of people worldwide, is biologically based and is not an imaginary disorder.

"We now have concrete evidence that RLS is an authentic disorder with recognizable features and underlying biological basis," says David Rye, MD, PhD, professor of neurology at Emory University School of Medicine, director of the Emory Healthcare Program in Sleep, and one of the study's lead authors.

"This is the most definitive link between genetics and RLS that has been reported to date. We have known for quite some time that the majority of RLS patients have a close family member with the disorder, and now we have found a gene which is clearly linked to RLS," added Dr. Rye.

To locate any genetic variants that could be responsible for RLS, a team led by Hreinn Stefansson of deCODE Genetics Inc who reported their findings in the New England Journal of Medicine looked at blood samples of more than 1,000 Icelanders and Americans, and then compared the DNA of study volunteers to the DNA of people without the symptom.

After four-year study, they linked a common gene variation to the periodic leg movements that occur during the night in most patients with RLS. Scientists say this variation in the human genome probably accounts for 50% of restless legs cases.

In the Nature Genetics, study researchers compared the DNA of 400 people with the family history of syndrome with the DNA of 1,600 people who had no symptoms of RLS. The study identified the same gene variation that was discovered by the first study and two others in Germans and Canadians with the sleep-robbing neurological disorder.

The researchers report that people with one genetic variant that was strongly associated with RLS with periodic limb movements were 50 percent more likely to have RLS. Nearly 65 percent of the population carries at least one copy of the variant, and people who carry two copies of this common variant are at significant risk of experiencing RLS, they noted.

According to Dr. Rye, it’s not necessary that people who carry two copies of the variant would develop symptoms of RLS.

"There remain yet-to-be-identified medical, environmental or genetic factors that appear necessary to translate genetic susceptibility into RLS symptoms," he says.

Restless legs syndrome is a twitching condition described as "jimmy legs" in a "Seinfeld" episode, and is characterized by unpleasant sensations in the limbs, generally the legs, that occur at rest or before sleep and are relieved by activity such as walking. In addition, RLS can cause difficulty in falling or staying asleep.

According to the Restless Legs Syndrome Foundation, a substantial number of people who have RLS also have periodic limb movements of sleep (PLMS). These are jerks that occur every 20 to 30 seconds on and off throughout the night. This can cause partial awakenings that disrupt sleep. Sleep deprivation can seriously impact your work, relationships, and health.

RLS is commonly treated with US health watchdog FDA-approved ropinirole (Requip) and pramipexole (Mirapex) drugs.

FDA, on May 5, 2005 gave its approval to GlaxoSmithKline PLC.-made Requip, making it the first drug for treatment of restless legs syndrome. In 2006, the health agency also approved pramipexole for treating moderate to severe primary restless legs syndrome.