Scientists have linked certain genes to restless legs syndrome, suggesting the twitching condition described as "jimmy legs" in a "Seinfeld" episode is biologically based and not an imaginary disorder.
New studies published this week in two top medical journals are being called the first to identify specific genes responsible for restless legs syndrome symptoms.
Research in the New England Journal of Medicine, linked a common gene variation to nighttime leg-twitching. It involved people in Iceland and the United States.
A second study in Nature Genetics identified the same gene variation and two others in Germans and Canadians with restless legs syndrome.
"This discovery demonstrates the power of genetics not only for uncovering the biological causes of disease, but also for defining diseases such as RLS and establishing them as medical conditions," said Dr. Kari Stefansson, in a prepared statement.
Stefansson is a prominent Icelandic scientist and a co-author of the New England Journal of Medicine study.
Restless legs syndrome is a neurological condition characterized by an irresistible urge to move the legs. Sufferers say it often hits at night, preventing them from sleeping.
"It feels like something crawling inside your legs, biting on you," said Betty Shaw, a 68-year-old florist in Covington, Georgia. She and her 43-year-old daughter were told they have RLS.
The condition gained cultural status through an oft-quoted episode of the sitcom "Seinfeld," in which the character Kramer is disturbed that his girlfriend has "the jimmy legs" and kicks in bed.
It’s commonly treated with two government-approved drugs, including the heavily advertised Requip, made by GlaxoSmithKline PLC. Sales of Requip hit about $500 million last year. Shaw takes the aqua-colored pill and says it’s the only thing that’s helped her.
The first study looked at blood samples from more than 1,000 Icelanders and Americans, comparing the DNA of leg twitchers to the DNA of people without the symptom. Scientists found a certain variation in the human genome that, they say, probably accounts for 50 percent of restless legs cases.
They also found that the variation was associated with lower iron levels, echoing — but not explaining — a relationship noted in earlier research.
The second study compared the DNA of 400 people with a family history of the syndrome with the DNA of 1,600 who did not. It found variations in three areas of the genome that each were responsible for a 50 percent increase in the risk for the syndrome.
More research is needed to develop a full explanation of the causes of restless legs syndrome. The New England Journal study indicates as many as 65 percent of adults carry the gene variation that can lead to symptoms, said Dr. David Rye, an Emory University neurologist who was another co-author.
"People making the argument that this can’t be very common — that’s just gone," said Rye, who himself has restless legs.
The syndrome is diagnosed through symptoms like periodic limb movements in sleep, but lots of people may have limb movements without having the condition, noted Dr. Steven Woloshin, a Dartmouth Medical School researcher who has argued the diagnosis is overhyped.
He argues that the best evidence puts the U.S. prevalence of restless legs at under 3 percent, less than common estimates of 10 percent.
The new research doesn’t pin down what the condition is, who has it, or what medication is needed, he wrote in an e-mail.