The study will appear in an upcoming print issue of Annals of Neurology, the research publication of the American Neurological Association.

Researchers at the Max Planck Institute of Psychiatry in Munich, Germany, found that when restless legs syndrome (RLS) appears before the age of 30, it is likely caused by a single, yet-unidentified gene. In cases in which the syndrome appears after the age of 30, a combination of various genes and environmental causes is probably to blame.

"We hope that this knowledge will help us to identify one or more genes that cause RLS and allow us to find a specific cure for the disease," said senior author Claudia Trenkwalder, M.D., now of the University of Göttingen in Germany.

Restless legs syndrome can cause discomfort in any of the limbs, but usually in the calves, associated with an urge to move. The discomfort, described as a "creepy crawly feeling," occurs when the person is at rest or trying to sleep, with the result that patients frequently report sleep deficits and day-time fatigue.

Overall, the disorder seems to affect about 3 percent of people under the age of 30, but climbs to 10 percent in people over the age of 65, and to 20 percent in those over the age of 80. Doctors do not know what causes the disorder, nor do they have a cure or effective treatment.

There is clearly an inherited component, as it seems to run in some families. It has generally been understood that roughly half the cases of RLS begin in middle age, with the other half beginning in childhood or early adulthood. This assumption is confirmed and given a genetic basis in the present study.

Trenkwalder, along with lead author Juliane Winkelmann, M.D., and their collaborators from several other institutions in Germany, studied 908 people, including 238 RLS patients and their close family members. They divided the families into two groups, depending on whether cases began before or after the age of 30.

By studying the genealogies of the patients and their families, they found strong evidence that a single gene transmits the disease in the families with an early age at onset. This mode of transmission is termed "autosomal dominant," meaning that the child -- male or female -- of an affected parent has a 50% chance of inheriting the defective gene.

By contrast, multiple genes and environmental factors are probably in play in those families where symptoms began after the age of 30.

"In the older patients, it is very likely that treatable diseases such as iron deficiency, uremia, diabetes, or polyneuropathy may induce or worsen RLS symptoms," said author Winkelmann.

(Reference: "Complex Segregation Analysis of Restless Legs Syndrome Provides Evidence for an Autosomal Dominant Mode of Inheritance in Early Age at Onset Families," Juliane Winkelmann, Bertram Muller-Myhsok, Hans-Ulrich Wittchen, Bettina Hock, Muriel Prager, Hildegard Pfister, Andreas Strohle, Ilonka Eisensehr, Martin Dichgans, Thomas Gasser, and Claudia Trenkwalder, Annals of Neurology.

Annals of Neurology is published by John Wiley & Sons on behalf of the American Neurological Association.

07-Jun-2002