Restless legs syndrome appears to aggregate in families, and the siblings of those who are severely affected appear to have an increased risk of developing the disease, according to a report in the May issue of Archives of Neurology, one of the JAMA/Archives journals.

Restless legs syndrome is primarily based on patient reports of symptoms, including an irresistible desire to move the legs, according to background information in the article. Some previous studies have suggested that the condition clusters in families. “However, there has been a lack of large-scale systematic family studies and of full descriptions of the clinical features of familial restless legs syndrome,” the authors write.

Lan Xiong, M.D., Ph.D., of the Research Centre of the University of Montreal Hospital Centre, Montreal, Canada, and colleagues studied 671 individuals who met the current standard diagnostic criteria for restless legs syndrome. This included 192 individuals who were assessed at a specialized sleep center and 479 affected family members who responded to a structured questionnaire telephone diagnostic interview.

The condition appeared to aggregate in families, with a familial rate of 77 percent, the authors note. Siblings of an individual with the condition were about 3.6 times more likely to have the disease than those without an affected sibling, and offspring of parents with the condition had 1.8 times the risk.

“Familial restless legs syndrome is a chronic disorder with a mean [average] disease duration of 24 years and a wide range of age of onset (average 28 years), with most family members having early-onset disease but mild to moderate restless legs syndrome symptoms,” the authors write. “Our clinical data also indicated that familial restless legs syndrome is more prominent among women who also had increased incidence of anemia/iron deficiency, arthritis and number of pregnancies.”

Aggregation of disease in families could be due to genetic influences, environmental effects or the combination of both, the authors note. “The dissection of the underlying genetic and non-genetic composition of the outstanding familial aggregation observed in restless legs syndrome should be interesting to all concerned physicians, geneticists and epidemiologists,” the authors write. “An enlarged, prospective population-based family study including exposure to environmental risk factors will allow a more precise quantification and delineation of the familiality of restless legs syndrome.”

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(Arch Neurol. 2010;67[5]:617-622. Available pre-embargo to the media at http://www.jamamedia.org.)

Editor’s Note: This project was supported by a grant from the Canadian Institutes of Health Research (CIHR), a research fellowship from the Restless Legs Syndrome Foundation and a CIHR doctoral studentship. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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