Restless Legs Syndrome Has Complex Genetic Involvement

Restless legs syndrome is one of the leading causes of insomnia, affecting more than five to 10 percent of the white population, according to background information in the article. Genetic contributions to restless legs syndrome have been consistently supported by population, family and twin studies. To identify genetic risk factors, the current study used information from French Canadian families, where, according to the researchers, prevalence of restless legs syndrome is higher than in other populations.

Alex Desautels, Ph.D., of the University of Montreal, and colleagues examined the DNA of 19 multigenerational French Canadian families with four to nine individuals who were affected (or possibly affected) by restless legs syndrome. The researchers used statistical analysis of the genetic information to determine whether restless legs syndrome in each family was linked with markers on the same location on chromosome 12q that had previously been associated with restless legs syndrome.

Two-hundred-seventy-six individuals were included in the study, including 146 affected individuals, 39 possibly affected individuals and 91 unaffected family members. The researchers confirmed that the syndrome was consistent with linkage to chromosome 12q within five families. Linkage to that location was formally excluded for six other families. The researchers compared clinical features of the syndrome in affected individuals from the different families to see if those differences correlated with the differences in linkage. They found that one feature, periodic leg movements during sleep, was significantly greater for affected individuals from the linked families than for affected individuals from the unlinked families.

"These results further support the involvement of an RLS-susceptibility locus [gene location] on chromosome 12q in the FC [French Canadian] population and also provide evidence that there must be other loci involved in this common sleep disorder," the authors conclude. "Furthermore, our findings illustrate that extensive characterization of subclinical differences represents a major tool in the identification of susceptibility loci for complex diseases … Although the background of RLS is most likely complex, this finding may offer a new starting point for further dissecting the genetic cause of RLS."

(Arch Neurol. 2005;62:591-596. Available post-embargo at archneurol.com)

Editor's Note: This study was supported in part by research grants from the Canadian Institutes of Health Research (CIHR), Ottawa and from the National Institutes of Health, Bethesda, Md. Dr. Desautels is a recipient of the CIHR studentship.