Thursday, July 19, 2007

Gene Linked to Restless Leg Syndrome Found

(HealthDay News) -- Icelandic researchers have discovered a gene that's linked to restless legs syndrome (RLS).

The research, which is in the July 19 issue of the New England Journal of Medicine, found a gene variant that increases the odds of having RLS with periodic limb movements during sleep by 50 percent. The researchers also found that those with the gene variant were more likely to have low iron levels.

"There is a strong familial and genetic basis to restless legs syndrome," said the author of an accompanying editorial, Dr. John Winkelman, medical director of the Sleep Health Center at Brigham and Women's Hospital in Boston.

Winkelman's editorial also pointed out that two other soon-to-be-published studies confirmed the link to this gene variant and RLS in a different population, and found two other genetic variants linked to RLS.

"Finding these genes may allow us to get more detail in the RLS story and eventually may allow us to predict who will respond to medications, who will have complications and which family members are likely to develop RLS. But it's early on; we need to see which of the next steps pan out, but this opens up many new avenues for research," Winkelman said.

Restless legs syndrome is a common neurological disorder, affecting as many as 3 percent of American adults, according to Winkelman. Those with RLS experience a compelling need to move their legs.

"It's quite a creepy, uncomfortable feeling. It's kind of a jittery feeling that they have to move their legs," explained Susan Zafarlotfi, clinical director of the Institute for Sleep-Wake Disorders and the Breath and Lung Institute at Hackensack University Medical Center in New Jersey.

About four out of five people with RLS also experience periodic limb movements during sleep, according to Winkelman. Periodic limb movements -- jerking or twitching of the legs or feet -- occur in a fairly set pattern, with a still period in between. "It almost looks as if they're guided by a metronome," said Winkelman. With each movement, blood pressure rises, and the person may be briefly aroused from sleep, though they're often not aware of this. Winkelman said many people with RLS have poor quality sleep and report daytime fatigue.

Many people with RLS also have family members with the disorder, suggesting a genetic component to the disease.

To locate any genetic variants that could be responsible for RLS, the researchers recruited 451 people who had symptoms of RLS, as well as 514 of their first-degree relatives.

The study volunteers filled out RLS questionnaires, had their periodic limb movements measured during sleep and gave blood samples.

The researchers found one genetic variant was strongly associated with RLS with periodic limb movements. To validate these findings, the researchers then compared a second sample of 123 Icelandic study participants to 1,233 controls.

Overall, people with that particular genetic variant were 50 percent more likely to have RLS with periodic limb movements. Because the association was stronger in people with RLS and periodic limb movements than in those with just RLS, the researchers and Winkelman believe this genetic variant is likely one associated with periodic limb movements.

The researchers also found that iron levels were significantly decreased -- by as much as 26 percent -- in those with the genetic variant.

"Iron is important in the brain in the regulation of dopamine function. Dopamine is a neurotransmitter that's at least partially responsible for regulating sensation and movement," said Winkelman, who added that medications that increase dopamine activity in the brain, such as ropinirole (Requip) or pramipexole (Mirapex), are effective in treating RLS.

Both Winkelman and Zafarlotfi said that there's an increasing awareness in the medical community of RLS as a disorder, and that people should definitely bring it up with their physician if they're having symptoms.

"Even if you were rebuffed originally when describing your symptoms, try again," advised Winkelman. He said an appropriate assessment includes checking blood levels of iron and reviewing what medications you're taking.

Zafarlotfi pointed out that some common medications, such as antidepressants, may increase RLS symptoms.

More information
To learn more about restless leg syndrome, visit the RLS Foundation.

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